liam murray | Queen's University Belfast (original) (raw)

Papers by liam murray

Research paper thumbnail of Statin Use and Survival from Lung Cancer: A Population-Based Cohort Study

Cancer Epidemiology Biomarkers & Prevention, 2015

Preclinical evidence from lung cancer cell lines and animal models suggest that statins could hav... more Preclinical evidence from lung cancer cell lines and animal models suggest that statins could have anticancer properties. We investigated whether statin users had reduced risk of cancer-specific mortality in a population-based cohort of lung cancer patients. Newly diagnosed lung cancer patients, from 1998 to 2009, were identified from English cancer registry data and linked to the UK Clinical Practice Research Datalink, providing prescription records, and to Office of National Statistics mortality data up to 2012. Cox regression models were used to calculate HRs for cancer-specific mortality and 95% confidence intervals (CI) by statin use before and after diagnosis, and to adjust these HRs for potential confounders. In 3,638 lung cancer patients, there was some evidence that statin use after diagnosis was associated with reduced lung cancer-specific mortality (adjusted HR, 0.89; 95% CI, 0.78-1.02; P = 0.09). Associations were more marked after 12 prescriptions (adjusted HR, 0.81; 95% CI, 0.67-0.98; P = 0.03) and when lipophilic statins were investigated (adjusted HR, 0.81; 95% CI, 0.70-0.94; P = 0.01), but were attenuated in some sensitivity analyses. Furthermore, in 11,051 lung cancer patients, statin use before diagnosis was associated with reduced lung cancer-specific mortality (adjusted HR, 0.88; 95% CI, 0.83-0.93; P < 0.001). There was some evidence that lung cancer patients who used statins, and particularly simvastatin, had reduced rates of cancer-specific mortality. These findings should first be confirmed in observational studies, but provide some support for conducting randomized controlled trials of simvastatin as adjuvant cancer therapy in lung cancer patients. Cancer Epidemiol Biomarkers Prev; 24(5); 833-41. ©2015 AACR.

Research paper thumbnail of Statin use after colorectal cancer diagnosis and survival: a population-based cohort study

Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2014

To investigate whether statins used after colorectal cancer diagnosis reduce the risk of colorect... more To investigate whether statins used after colorectal cancer diagnosis reduce the risk of colorectal cancer-specific mortality in a cohort of patients with colorectal cancer. A cohort of 7,657 patients with newly diagnosed stage I to III colorectal cancer were identified from 1998 to 2009 from the National Cancer Data Repository (comprising English cancer registry data). This cohort was linked to the United Kingdom Clinical Practice Research Datalink, which provided prescription records, and to mortality data from the Office of National Statistics (up to 2012) to identify 1,647 colorectal cancer-specific deaths. Time-dependent Cox regression models were used to calculate hazard ratios (HR) for cancer-specific mortality and 95% CIs by postdiagnostic statin use and to adjust these HRs for potential confounders. Overall, statin use after a diagnosis of colorectal cancer was associated with reduced colorectal cancer-specific mortality (fully adjusted HR, 0.71; 95% CI, 0.61 to 0.84). A do...

Research paper thumbnail of Prevalence of epigastric pain, heartburn and acid regurgitation in adolescents and their parents: evidence for intergenerational association

European journal of gastroenterology & hepatology, 2007

Little is known of the epidemiology of upper gastrointestinal symptoms in adolescents. We examine... more Little is known of the epidemiology of upper gastrointestinal symptoms in adolescents. We examined the prevalence of, and the risk factors for, epigastric pain, heartburn and acid regurgitation in adolescents from Northern Ireland. A total of 1133 adolescents aged 12-18 years participated in this study. Questionnaires were mailed to 2017 randomly selected individuals gathering information on symptoms of epigastric pain, heartburn and acid regurgitation. Prevalences of the symptoms in the individuals and their parents were calculated. Associations between potential risk factors such as age, sex, body mass index category, smoking and frequency of symptoms were examined for both adolescents and their parents. Logistic regression was used to examine the relationship between adolescent and parental symptoms. Symptoms of epigastric pain, heartburn and acid regurgitation were infrequent in adolescents, but were substantially more common in parents. Adolescents were more likely to experienc...

Research paper thumbnail of Inverse relationship between alcohol consumption and active Helicobacter pylori infection: the Bristol Helicobacter project

The American journal of gastroenterology, 2002

The aim of this study was to examine whether smoking or consumption of alcohol or coffee is assoc... more The aim of this study was to examine whether smoking or consumption of alcohol or coffee is associated with active Helicobacter pylori (H. pylori) infection. This was a cross-sectional population study conducted as part of a randomized controlled trial of H. pylori infection eradication in southwest England. A total of 10,537 subjects, recruited from seven general practices, underwent 13C-urea breath testing for active infection with H. pylori and provided data on smoking, usual weekly consumption of alcohol, and daily intake of coffee. Smoking or coffee consumption were not related to active H. pylori infection. Total alcohol consumption was associated with a small, but not statistically significant, decrease in the odds of infection. After adjustment for age, sex, ethnic status, childhood and adult social class, smoking, coffee consumption, and intake of alcoholic beverages other than wine, subjects drinking 3-6 units of wine/wk had an 11% lower risk of H. pylori infection compare...

Research paper thumbnail of Lifestyle factors and small intestine adenocarcinoma risk: A systematic review and meta-analysis

Cancer Epidemiology, 2015

Although the incidence of small intestinal adenocarcinoma (SIA) is low, rates are increasing and ... more Although the incidence of small intestinal adenocarcinoma (SIA) is low, rates are increasing and little information regarding modifiable lifestyle risk factors is available. To provide a systematic review of lifestyle factors and SIA risk. Ovid MEDLINE, EMBASE and Web of science were searched from inception to week 1 October 2013. Nine publications that reported on SIA risk in relation to alcohol intake (n=6), tobacco smoking (n=6), diet (n=5), body mass (n=3), physical activity (n=1), hormone use (n=1) and/or socio-economic status (n=3) were retrieved. Results for alcohol, smoking and SIA risk were pooled using random-effects meta-analyses to produce relative risks (RR) and 95% confidence intervals (CI). The summary RR for individuals consuming the highest versus lowest category of alcohol intake was 1.51 (95% CI 0.83-2.75; n=5 studies) with significant increased risks emerging in sensitivity analysis with reduced heterogeneity (RR: 1.82, 95% CI: 1.05-3.15; n=4 studies). The pooled SIA RR for individuals in the highest versus lowest category of smoking was 1.24 (95% CI 0.71-2.17; n=5 studies). In relation to dietary factors, high fibre intakes and normal body weight may be protective, while high intakes of red/processed meat and sugary drinks may increase SIA risk. Evidence on socio-economic status and SIA risk was equivocal. Data on other factors were too sparse to draw any conclusions. Alcohol may be associated with an increased risk of SIA. Further investigation of lifestyle factors, particularly alcohol, smoking and diet, in the aetiology of this cancer is warranted in large consortial studies.

Research paper thumbnail of Reply to U. Ravnskov et al, D. Tural et al, and M.A.N. Şendur et al

Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Jan 20, 2015

Research paper thumbnail of Dietary patterns and cardiovascular risk factors in adolescents and young adults: the Northern Ireland Young Hearts Project

British Journal of Nutrition, 2014

Dietary pattern (DP) analysis allows examination of the combined effects of nutrients and foods o... more Dietary pattern (DP) analysis allows examination of the combined effects of nutrients and foods on the markers of CVD. Very few studies have examined these relationships during adolescence or young adulthood. Traditional CVD risk biomarkers were analysed in 12-15-year-olds (n 487; Young Hearts (YH)1) and again in the same individuals at 20-25 years of age (n 487; YH3). Based on 7 d diet histories, in the present study, DP analysis was performed using a posteriori principal component analysis for the YH3 cohort and the a priori Mediterranean Diet Score (MDS) was calculated for both YH1 and YH3 cohorts. In the a posteriori DP analysis, YH3 participants adhering most closely to the 'healthy' DP were found to have lower pulse wave velocity (PWV) and homocysteine concentrations, the 'sweet tooth' DP were found to have increased LDL concentrations, systolic blood pressure, and diastolic blood pressure and decreased HDL concentrations, the 'drinker/social' DP were found to have lower LDL and homocysteine concentrations, but exhibited a trend towards a higher TAG concentration, and finally the 'Western' DP were found to have elevated homocysteine and HDL concentrations. In the a priori dietary score analysis, YH3 participants adhering most closely to the Mediterranean diet were found to exhibit a trend towards a lower PWV. MDS did not track between YH1 and YH3, and nor was there a longitudinal relationship between the change in the MDS and the change in CVD risk biomarkers. In conclusion, cross-sectional analysis revealed that some associations between DP and CVD risk biomarkers were already evident in the young adult population, namely the association between the healthy DP (and the MDS) and PWV; however, no longitudinal associations were observed between these relatively short time periods.

Research paper thumbnail of Inverse relationship between alcohol consumption and active Helicobacter pylori infection: the Bristol Helicobacter project

The American Journal of Gastroenterology, 2002

The aim of this study was to examine whether smoking or consumption of alcohol or coffee is assoc... more The aim of this study was to examine whether smoking or consumption of alcohol or coffee is associated with active Helicobacter pylori (H. pylori) infection. This was a cross-sectional population study conducted as part of a randomized controlled trial of H. pylori infection eradication in southwest England. A total of 10,537 subjects, recruited from seven general practices, underwent 13C-urea breath testing for active infection with H. pylori and provided data on smoking, usual weekly consumption of alcohol, and daily intake of coffee. Smoking or coffee consumption were not related to active H. pylori infection. Total alcohol consumption was associated with a small, but not statistically significant, decrease in the odds of infection. After adjustment for age, sex, ethnic status, childhood and adult social class, smoking, coffee consumption, and intake of alcoholic beverages other than wine, subjects drinking 3-6 units of wine/wk had an 11% lower risk of H. pylori infection compared with those who took no wine: OR = 0.89, 95% CI = 0.80-0.99. Higher wine consumption was associated with a further 6% reduction in the risk of infection: OR = 0.83, 95% CI = 0.64-1.07. Intake of 3-6 units of beer (but no greater intake) was associated with a similar reduction in the risk of infection when compared to no beer intake (OR = 0.83, 95% CI = 0.75-0.91). This study indicates that modest consumption of wine and beer (approximately 7 units/wk) protects against H. pylori infection, presumably by facilitating eradication of the organism.

Research paper thumbnail of Gastroesophageal Reflux in Relation to Adenocarcinomas of the Esophagus: A Pooled Analysis from the Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON)

PLoS ONE, 2014

Background: Previous studies have evidenced an association between gastroesophageal reflux and es... more Background: Previous studies have evidenced an association between gastroesophageal reflux and esophageal adenocarcinoma (EA). It is unknown to what extent these associations vary by population, age, sex, body mass index, and cigarette smoking, or whether duration and frequency of symptoms interact in predicting risk. The Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) allowed an in-depth assessment of these issues.

Research paper thumbnail of Alcohol and the Risk of Barrett's Esophagus: A Pooled Analysis from the International BEACON Consortium

The American Journal of Gastroenterology, 2014

Results from studies examining the association between alcohol consumption and the risk of Barret... more Results from studies examining the association between alcohol consumption and the risk of Barrett's esophagus have been inconsistent. We assessed the risk of Barrett's esophagus associated with total and beverage-specific alcohol consumption by pooling individual participant data from five case-control studies participating in the international Barrett's and Esophageal Adenocarcinoma Consortium. For analysis, there were 1,282 population-based controls, 1,418 controls with gastroesophageal reflux disease (GERD), and 1,169 patients with Barrett's esophagus (cases). We estimated study-specific odds ratios (ORs) and 95% confidence intervals (95% CI) using multivariable logistic regression models adjusted for age, sex, body mass index (BMI), education, smoking status, and GERD symptoms. Summary risk estimates were obtained by random-effects models. We also examined potential effect modification by sex, BMI, GERD symptoms, and cigarette smoking. For comparisons with population-based controls, although there was a borderline statistically significant inverse association between any alcohol consumption and the risk of Barrett's esophagus (any vs. none, summary OR=0.77, 95% CI=0.60-1.00), risk did not decrease in a dose-response manner (Ptrend=0.72). Among alcohol types, wine was associated with a moderately reduced risk of Barrett's esophagus (any vs. none, OR=0.71, 95% CI=0.52-0.98); however, there was no consistent dose-response relationship (Ptrend=0.21). We found no association with alcohol consumption when cases were compared with GERD controls. Similar associations were observed across all strata of BMI, GERD symptoms, and cigarette smoking. Consistent with findings for esophageal adenocarcinoma, we found no evidence that alcohol consumption increases the risk of Barrett's esophagus.

Research paper thumbnail of An exploratory study on risk factors for chronic non-communicable diseases among adolescents in Malaysia: overview of the Malaysian Health and Adolescents Longitudinal Research Team study (The MyHeART study)

BMC Public Health, 2014

Background: The National Health & Morbidity Survey (NHMS) IV (2011) observed that the prevalence ... more Background: The National Health & Morbidity Survey (NHMS) IV (2011) observed that the prevalence of obese children aged less than 18 years in Malaysia is 6.1% compared to 5.4% overweight and obese in NHMS III (2006). As such, this observation is of public health importance as obesity is a forewarning risk factor for chronic diseases such as type-2 diabetes, cardiovascular diseases (CVD) and certain types of cancers. This MyHeART (Malaysian Health and Adolescents longitudinal Research Team) study aims to examine risk factors of non-communicable diseases (NCD) among adolescents.

Research paper thumbnail of Association between self-reported physical activity and indicators of body composition in Malaysian adolescents

Preventive Medicine, 2014

Obesity and lack of physical activity are fast becoming a concern among Malaysian adolescents. Th... more Obesity and lack of physical activity are fast becoming a concern among Malaysian adolescents. This study aims to assess physical activity levels among Malaysian adolescents and investigate the association between physical activity levels and body composition such as body mass index (BMI), waist circumference (WC) and percentage of body fat. 1361 school-going 13 year old multi-ethnic adolescents from population representative samples in Malaysia were involved in our study. Self-reported physical activity levels were assessed using the validated Malay version of the Physical Activity Questionnaire for Older Children (PAQ-C). Height, weight, body fat composition and waist circumference (WC) were measured. Data collection period was from March to May 2012. 10.8% of the males and 7.4% of the females were obese according to the International Obesity Task Force standards. A majority of the adolescents (63.9%) were physically inactive. There is a weak but significant correlation between physical activity scores and the indicators of obesity. The adjusted coefficient for body fatness was relatively more closely correlated to physical activity scores followed by waist circumference and lastly BMI. This study demonstrates that high physical activity scores were associated with the decreased precursor risk factors of obesity.

Research paper thumbnail of Fitness level and body composition indices: cross-sectional study among Malaysian adolescent

BMC Public Health, 2014

The importance of fitness level on the well-being of children and adolescent has long been recogn... more The importance of fitness level on the well-being of children and adolescent has long been recognised. The aim of this study was to investigate the fitness level of school-going Malaysian adolescent, and its association with body composition indices. Methods: 1071 healthy secondary school students participated in the fitness assessment for the Malaysian Health and Adolescents Longitudinal Research Team (MyHEART) study. Body composition indices such as body mass index for age, waist circumference and waist height ratio were measured. Fitness level was assessed with Modified Harvard Step Test. Physical Fitness Score was calculated using total time of step test exercise and resting heart rates. Fitness levels were divided into 3 categories -unacceptable, marginally acceptable, and acceptable. Partial correlation analysis was used to determine the association between fitness score and body composition, by controlling age, gender, locality, ethnicity, smoking status and sexual maturation. Multiple regression analysis was conducted to determine which body composition was the strongest predictor for fitness. Results: 43.3% of the participants were categorised into the unacceptable fitness group, 47.1% were considered marginally acceptable, and 9.6% were acceptable. There was a significant moderate inverse association (p < 0.001) between body composition with fitness score (r = -0.360, -0.413 and -0.403 for body mass index for age, waist circumference and waist height ratio, respectively). Waist circumference was the strongest and significant predictor for fitness (ß = -0.318, p = 0.002). Conclusion: Only 9.6% of the students were fit. There was also an inverse association between body composition and fitness score among apparently healthy adolescents, with waist circumference indicated as the strongest predictor. The low fitness level among the Malaysian adolescent should necessitate the value of healthy lifestyle starting at a young age.

Research paper thumbnail of Metabolic syndrome among 13 year old adolescents: prevalence and risk factors

BMC Public Health, 2014

Background: Obesity and metabolic syndrome is prevalent among Malaysian adolescents and has been ... more Background: Obesity and metabolic syndrome is prevalent among Malaysian adolescents and has been associated with certain behavioural factors such as duration of sleep, screen time and physical activity. The aim of the study is to report the prevalence of overweight/obesity, metabolic syndrome and its risk factors among adolescents. Methods: A multi-staged cluster sampling method was used to select participants from urban and rural schools in Selangor, Perak and Wilayah Persekutuan Kuala Lumpur. Participants underwent anthropometric measurement and physical examination including blood pressure measurement. Blood samples were taken for fasting glucose and lipids and participants answered a self-administered questionnaire. Overweight and obesity was defined using the extrapolated adult body mass index (BMI) cut-offs of >25 kg/m 2 and >30 kg/m 2 , according to the International Obesity Task Force (IOTF) criteria. Metabolic syndrome was defined based on International Diabetes Federation (IDF) 2007 criteria.

Research paper thumbnail of The effectiveness of a life style modification and peer support home blood pressure monitoring in control of hypertension: protocol for a cluster randomized controlled trial

BMC public health, 2014

Death rates due to hypertension in low and middle income countries are higher compared to high in... more Death rates due to hypertension in low and middle income countries are higher compared to high income countries. The present study is designed to combine life style modification and home blood pressure monitoring for control of hypertension in the context of low and middle income countries. The study is a two armed, parallel group, un-blinded, cluster randomized controlled trial undertaken within lower income areas in Kuala Lumpur. Two housing complexes will be assigned to the intervention group and the other two housing complexes will be allocated in the control group. Based on power analysis, 320 participants will be recruited. The participants in the intervention group (n = 160) will undergo three main components in the intervention which are the peer support for home blood pressure monitoring, face to face health coaching on healthy diet and demonstration and training for indoor home based exercise activities while the control group will receive a pamphlet containing information...

Research paper thumbnail of Intakes of Dietary Folate and Other B Vitamins Are Associated with Risks of Esophageal Adenocarcinoma, Barrett's Esophagus, and Reflux Esophagitis

Journal of Nutrition, 2013

Folate is implicated in carcinogenesis via effects on DNA synthesis, repair, and methylation. Eff... more Folate is implicated in carcinogenesis via effects on DNA synthesis, repair, and methylation. Efficient folate metabolism requires other B vitamins and is adversely affected by smoking and alcohol. Esophageal adenocarcinoma (EAC) may develop through a process involving inflammation [reflux esophagitis (RE)] leading to metaplasia [Barrett&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s esophagus (BE)] and carcinoma. Within a population-based, case-control study, we investigated associations between dietary folate and related factors and risks of EAC, BE, and RE. EAC and BE cases had histologically confirmed disease; RE cases had endoscopically visible inflammation. Controls, age-sex frequency matched to EAC cases, were selected through population and general practice registers. Participants underwent structured interviews and completed food-frequency questionnaires. Multivariate ORs and 95% CIs were computed using logistic regression. A total of 256 controls and 223 EAC, 220 BE, and 219 RE cases participated. EAC risk decreased with increasing folate intake (OR highest vs. lowest = 0.56; 95% CI: 0.31, 1.00; P-trend &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01). Similar trends were found for BE (P-trend &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01) and RE (P-trend = 0.01). Vitamin B-6 intake was significantly inversely related to risks of all 3 lesions. Riboflavin intake was inversely associated with RE. Vitamin B-12 intake was positively associated with EAC. For EAC, there was a borderline significant interaction between folate intake and smoking (P-interaction = 0.053); compared with nonsmokers with high (≥ median) folate intake, current smokers with low intakes (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;median) had an 8-fold increased risk (OR: 8.15; 95% CI: 3.61, 18.40). The same group had increased BE risk (OR: 2.93; 95% CI: 1.24, 6.92; P-interaction = 0.12). Folate and other dietary methyl-group factors are implicated in the etiology of EAC and its precursors.

Research paper thumbnail of A longitudinal study through adolescence to adulthood

Public Health, 2002

The Young Hearts (YH) Project is an ongoing study of biological and behavioural risk factors for ... more The Young Hearts (YH) Project is an ongoing study of biological and behavioural risk factors for cardiovascular disease in a representative sample of young people from Northern Ireland, a region of high coronary mortality. This article describes the cross-sectional clinical, dietary and lifestyle data obtained from individuals (aged 20-25 y) who participated in phase 3 of the project (YH3). A total of 489 individuals (251 males, 238 females) participated in YH3 (48.2% response rate). Some 31.1% of participants at YH3 were overweight (BMI &amp;amp;amp;amp;amp;amp;gt;25 kg/m(2)) with 4.4% of males and 8.0% of females were obese (BMI &amp;amp;amp;amp;amp;amp;gt;30 kg/m(2)). More females than males had a very poor fitness (55.0 vs 22.1%, chi-squared 51.70, d.f. 1, P&amp;amp;amp;amp;amp;amp;lt;0.001) and did not participate in any sporting or exercise activity (38.4 vs 24.9%, chi-squared 10.26, d.f. 1, P=0.001). Over 20% of participants had a raised total serum cholesterol (&amp;amp;amp;amp;amp;amp;gt;5.2 mmol/l). More females had a raised serum LDL-cholesterol (&amp;amp;amp;amp;amp;amp;gt;3.0 mmol/l) than males (44.6 vs 34.6%, chi-squared 4.39, d.f. 1, P&amp;amp;amp;amp;amp;amp;lt;0.05). Over 46% of participants reported energy intakes from fat above recommended levels, and 68.5% of participants had saturated fat intakes above those recommended (Dietary reference values for food energy and nutrients for the United Kingdom. HMSO: London, 1991). Just over half of the study population reported alcohol intakes in excess of recommended sensible limits set by the Royal College of Physicians (A great and growing evil: the medical consequences of alcohol abuse. Tavistock: London, 1987), with 36.7% of males and 13.4% of females reporting intakes over twice these recommended limits. A total of 37% of the study population smoked. During young adulthood, individuals may be less amenable to attend a health-related study and recruitment of participants to the current phase of the study proved a major problem. However, these data constitute a unique developmental record from adolescence to young adulthood in a cohort from Northern Ireland and provide additional information on the impact of early life, childhood and young adulthood on the development of risk for chronic disease.

Research paper thumbnail of The Correlates of Body Composition with Heart Rate Recovery after Step Test: An Exploratory Study of Malaysian Adolescents

PLoS ONE, 2013

In adults, heart rate recovery is a predictor of mortality, while in adolescents it is associated... more In adults, heart rate recovery is a predictor of mortality, while in adolescents it is associated with cardio-metabolic risk factors. The aim of this study was to examine the relationship between body composition measures and heart rate recovery (HRR) after step test in Malaysian secondary school students.

Research paper thumbnail of A genome-wide association study identifies new susceptibility loci for non-cardia gastric cancer at 3q13.31 and 5p13.1

Research paper thumbnail of A map of human genome variation from population-scale sequencing

Nature, 2011

The 1000 Genomes Project aims to provide a deep characterization of human genome sequence variati... more The 1000 Genomes Project aims to provide a deep characterization of human genome sequence variation as a foundation for investigating the relationship between genotype and phenotype. Here we present results of the pilot phase of the project, designed to develop and compare different strategies for genome-wide sequencing with high-throughput platforms. We undertook three projects: low-coverage whole-genome sequencing of 179 individuals from four populations; high-coverage sequencing of two mother-father-child trios; and exon-targeted sequencing of 697 individuals from seven populations. We describe the location, allele frequency and local haplotype structure of approximately 15 million single nucleotide polymorphisms, 1 million short insertions and deletions, and 20,000 structural variants, most of which were previously undescribed. We show that, because we have catalogued the vast majority of common variation, over 95% of the currently accessible variants found in any individual are present in this data set. On average, each person is found to carry approximately 250 to 300 loss-of-function variants in annotated genes and 50 to 100 variants previously implicated in inherited disorders. We demonstrate how these results can be used to inform association and functional studies. From the two trios, we directly estimate the rate of de novo germline base substitution mutations to be approximately 10 28 per base pair per generation. We explore the data with regard to signatures of natural selection, and identify a marked reduction of genetic variation in the neighbourhood of genes, due to selection at linked sites. These methods and public data will support the next phase of human genetic research.

Research paper thumbnail of Statin Use and Survival from Lung Cancer: A Population-Based Cohort Study

Cancer Epidemiology Biomarkers & Prevention, 2015

Preclinical evidence from lung cancer cell lines and animal models suggest that statins could hav... more Preclinical evidence from lung cancer cell lines and animal models suggest that statins could have anticancer properties. We investigated whether statin users had reduced risk of cancer-specific mortality in a population-based cohort of lung cancer patients. Newly diagnosed lung cancer patients, from 1998 to 2009, were identified from English cancer registry data and linked to the UK Clinical Practice Research Datalink, providing prescription records, and to Office of National Statistics mortality data up to 2012. Cox regression models were used to calculate HRs for cancer-specific mortality and 95% confidence intervals (CI) by statin use before and after diagnosis, and to adjust these HRs for potential confounders. In 3,638 lung cancer patients, there was some evidence that statin use after diagnosis was associated with reduced lung cancer-specific mortality (adjusted HR, 0.89; 95% CI, 0.78-1.02; P = 0.09). Associations were more marked after 12 prescriptions (adjusted HR, 0.81; 95% CI, 0.67-0.98; P = 0.03) and when lipophilic statins were investigated (adjusted HR, 0.81; 95% CI, 0.70-0.94; P = 0.01), but were attenuated in some sensitivity analyses. Furthermore, in 11,051 lung cancer patients, statin use before diagnosis was associated with reduced lung cancer-specific mortality (adjusted HR, 0.88; 95% CI, 0.83-0.93; P &amp;amp;amp;amp;amp;amp;lt; 0.001). There was some evidence that lung cancer patients who used statins, and particularly simvastatin, had reduced rates of cancer-specific mortality. These findings should first be confirmed in observational studies, but provide some support for conducting randomized controlled trials of simvastatin as adjuvant cancer therapy in lung cancer patients. Cancer Epidemiol Biomarkers Prev; 24(5); 833-41. ©2015 AACR.

Research paper thumbnail of Statin use after colorectal cancer diagnosis and survival: a population-based cohort study

Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2014

To investigate whether statins used after colorectal cancer diagnosis reduce the risk of colorect... more To investigate whether statins used after colorectal cancer diagnosis reduce the risk of colorectal cancer-specific mortality in a cohort of patients with colorectal cancer. A cohort of 7,657 patients with newly diagnosed stage I to III colorectal cancer were identified from 1998 to 2009 from the National Cancer Data Repository (comprising English cancer registry data). This cohort was linked to the United Kingdom Clinical Practice Research Datalink, which provided prescription records, and to mortality data from the Office of National Statistics (up to 2012) to identify 1,647 colorectal cancer-specific deaths. Time-dependent Cox regression models were used to calculate hazard ratios (HR) for cancer-specific mortality and 95% CIs by postdiagnostic statin use and to adjust these HRs for potential confounders. Overall, statin use after a diagnosis of colorectal cancer was associated with reduced colorectal cancer-specific mortality (fully adjusted HR, 0.71; 95% CI, 0.61 to 0.84). A do...

Research paper thumbnail of Prevalence of epigastric pain, heartburn and acid regurgitation in adolescents and their parents: evidence for intergenerational association

European journal of gastroenterology & hepatology, 2007

Little is known of the epidemiology of upper gastrointestinal symptoms in adolescents. We examine... more Little is known of the epidemiology of upper gastrointestinal symptoms in adolescents. We examined the prevalence of, and the risk factors for, epigastric pain, heartburn and acid regurgitation in adolescents from Northern Ireland. A total of 1133 adolescents aged 12-18 years participated in this study. Questionnaires were mailed to 2017 randomly selected individuals gathering information on symptoms of epigastric pain, heartburn and acid regurgitation. Prevalences of the symptoms in the individuals and their parents were calculated. Associations between potential risk factors such as age, sex, body mass index category, smoking and frequency of symptoms were examined for both adolescents and their parents. Logistic regression was used to examine the relationship between adolescent and parental symptoms. Symptoms of epigastric pain, heartburn and acid regurgitation were infrequent in adolescents, but were substantially more common in parents. Adolescents were more likely to experienc...

Research paper thumbnail of Inverse relationship between alcohol consumption and active Helicobacter pylori infection: the Bristol Helicobacter project

The American journal of gastroenterology, 2002

The aim of this study was to examine whether smoking or consumption of alcohol or coffee is assoc... more The aim of this study was to examine whether smoking or consumption of alcohol or coffee is associated with active Helicobacter pylori (H. pylori) infection. This was a cross-sectional population study conducted as part of a randomized controlled trial of H. pylori infection eradication in southwest England. A total of 10,537 subjects, recruited from seven general practices, underwent 13C-urea breath testing for active infection with H. pylori and provided data on smoking, usual weekly consumption of alcohol, and daily intake of coffee. Smoking or coffee consumption were not related to active H. pylori infection. Total alcohol consumption was associated with a small, but not statistically significant, decrease in the odds of infection. After adjustment for age, sex, ethnic status, childhood and adult social class, smoking, coffee consumption, and intake of alcoholic beverages other than wine, subjects drinking 3-6 units of wine/wk had an 11% lower risk of H. pylori infection compare...

Research paper thumbnail of Lifestyle factors and small intestine adenocarcinoma risk: A systematic review and meta-analysis

Cancer Epidemiology, 2015

Although the incidence of small intestinal adenocarcinoma (SIA) is low, rates are increasing and ... more Although the incidence of small intestinal adenocarcinoma (SIA) is low, rates are increasing and little information regarding modifiable lifestyle risk factors is available. To provide a systematic review of lifestyle factors and SIA risk. Ovid MEDLINE, EMBASE and Web of science were searched from inception to week 1 October 2013. Nine publications that reported on SIA risk in relation to alcohol intake (n=6), tobacco smoking (n=6), diet (n=5), body mass (n=3), physical activity (n=1), hormone use (n=1) and/or socio-economic status (n=3) were retrieved. Results for alcohol, smoking and SIA risk were pooled using random-effects meta-analyses to produce relative risks (RR) and 95% confidence intervals (CI). The summary RR for individuals consuming the highest versus lowest category of alcohol intake was 1.51 (95% CI 0.83-2.75; n=5 studies) with significant increased risks emerging in sensitivity analysis with reduced heterogeneity (RR: 1.82, 95% CI: 1.05-3.15; n=4 studies). The pooled SIA RR for individuals in the highest versus lowest category of smoking was 1.24 (95% CI 0.71-2.17; n=5 studies). In relation to dietary factors, high fibre intakes and normal body weight may be protective, while high intakes of red/processed meat and sugary drinks may increase SIA risk. Evidence on socio-economic status and SIA risk was equivocal. Data on other factors were too sparse to draw any conclusions. Alcohol may be associated with an increased risk of SIA. Further investigation of lifestyle factors, particularly alcohol, smoking and diet, in the aetiology of this cancer is warranted in large consortial studies.

Research paper thumbnail of Reply to U. Ravnskov et al, D. Tural et al, and M.A.N. Şendur et al

Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Jan 20, 2015

Research paper thumbnail of Dietary patterns and cardiovascular risk factors in adolescents and young adults: the Northern Ireland Young Hearts Project

British Journal of Nutrition, 2014

Dietary pattern (DP) analysis allows examination of the combined effects of nutrients and foods o... more Dietary pattern (DP) analysis allows examination of the combined effects of nutrients and foods on the markers of CVD. Very few studies have examined these relationships during adolescence or young adulthood. Traditional CVD risk biomarkers were analysed in 12-15-year-olds (n 487; Young Hearts (YH)1) and again in the same individuals at 20-25 years of age (n 487; YH3). Based on 7 d diet histories, in the present study, DP analysis was performed using a posteriori principal component analysis for the YH3 cohort and the a priori Mediterranean Diet Score (MDS) was calculated for both YH1 and YH3 cohorts. In the a posteriori DP analysis, YH3 participants adhering most closely to the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;healthy&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; DP were found to have lower pulse wave velocity (PWV) and homocysteine concentrations, the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;sweet tooth&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; DP were found to have increased LDL concentrations, systolic blood pressure, and diastolic blood pressure and decreased HDL concentrations, the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;drinker/social&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; DP were found to have lower LDL and homocysteine concentrations, but exhibited a trend towards a higher TAG concentration, and finally the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;Western&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; DP were found to have elevated homocysteine and HDL concentrations. In the a priori dietary score analysis, YH3 participants adhering most closely to the Mediterranean diet were found to exhibit a trend towards a lower PWV. MDS did not track between YH1 and YH3, and nor was there a longitudinal relationship between the change in the MDS and the change in CVD risk biomarkers. In conclusion, cross-sectional analysis revealed that some associations between DP and CVD risk biomarkers were already evident in the young adult population, namely the association between the healthy DP (and the MDS) and PWV; however, no longitudinal associations were observed between these relatively short time periods.

Research paper thumbnail of Inverse relationship between alcohol consumption and active Helicobacter pylori infection: the Bristol Helicobacter project

The American Journal of Gastroenterology, 2002

The aim of this study was to examine whether smoking or consumption of alcohol or coffee is assoc... more The aim of this study was to examine whether smoking or consumption of alcohol or coffee is associated with active Helicobacter pylori (H. pylori) infection. This was a cross-sectional population study conducted as part of a randomized controlled trial of H. pylori infection eradication in southwest England. A total of 10,537 subjects, recruited from seven general practices, underwent 13C-urea breath testing for active infection with H. pylori and provided data on smoking, usual weekly consumption of alcohol, and daily intake of coffee. Smoking or coffee consumption were not related to active H. pylori infection. Total alcohol consumption was associated with a small, but not statistically significant, decrease in the odds of infection. After adjustment for age, sex, ethnic status, childhood and adult social class, smoking, coffee consumption, and intake of alcoholic beverages other than wine, subjects drinking 3-6 units of wine/wk had an 11% lower risk of H. pylori infection compared with those who took no wine: OR = 0.89, 95% CI = 0.80-0.99. Higher wine consumption was associated with a further 6% reduction in the risk of infection: OR = 0.83, 95% CI = 0.64-1.07. Intake of 3-6 units of beer (but no greater intake) was associated with a similar reduction in the risk of infection when compared to no beer intake (OR = 0.83, 95% CI = 0.75-0.91). This study indicates that modest consumption of wine and beer (approximately 7 units/wk) protects against H. pylori infection, presumably by facilitating eradication of the organism.

Research paper thumbnail of Gastroesophageal Reflux in Relation to Adenocarcinomas of the Esophagus: A Pooled Analysis from the Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON)

PLoS ONE, 2014

Background: Previous studies have evidenced an association between gastroesophageal reflux and es... more Background: Previous studies have evidenced an association between gastroesophageal reflux and esophageal adenocarcinoma (EA). It is unknown to what extent these associations vary by population, age, sex, body mass index, and cigarette smoking, or whether duration and frequency of symptoms interact in predicting risk. The Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) allowed an in-depth assessment of these issues.

Research paper thumbnail of Alcohol and the Risk of Barrett's Esophagus: A Pooled Analysis from the International BEACON Consortium

The American Journal of Gastroenterology, 2014

Results from studies examining the association between alcohol consumption and the risk of Barret... more Results from studies examining the association between alcohol consumption and the risk of Barrett&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s esophagus have been inconsistent. We assessed the risk of Barrett&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s esophagus associated with total and beverage-specific alcohol consumption by pooling individual participant data from five case-control studies participating in the international Barrett&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s and Esophageal Adenocarcinoma Consortium. For analysis, there were 1,282 population-based controls, 1,418 controls with gastroesophageal reflux disease (GERD), and 1,169 patients with Barrett&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s esophagus (cases). We estimated study-specific odds ratios (ORs) and 95% confidence intervals (95% CI) using multivariable logistic regression models adjusted for age, sex, body mass index (BMI), education, smoking status, and GERD symptoms. Summary risk estimates were obtained by random-effects models. We also examined potential effect modification by sex, BMI, GERD symptoms, and cigarette smoking. For comparisons with population-based controls, although there was a borderline statistically significant inverse association between any alcohol consumption and the risk of Barrett&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s esophagus (any vs. none, summary OR=0.77, 95% CI=0.60-1.00), risk did not decrease in a dose-response manner (Ptrend=0.72). Among alcohol types, wine was associated with a moderately reduced risk of Barrett&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s esophagus (any vs. none, OR=0.71, 95% CI=0.52-0.98); however, there was no consistent dose-response relationship (Ptrend=0.21). We found no association with alcohol consumption when cases were compared with GERD controls. Similar associations were observed across all strata of BMI, GERD symptoms, and cigarette smoking. Consistent with findings for esophageal adenocarcinoma, we found no evidence that alcohol consumption increases the risk of Barrett&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s esophagus.

Research paper thumbnail of An exploratory study on risk factors for chronic non-communicable diseases among adolescents in Malaysia: overview of the Malaysian Health and Adolescents Longitudinal Research Team study (The MyHeART study)

BMC Public Health, 2014

Background: The National Health & Morbidity Survey (NHMS) IV (2011) observed that the prevalence ... more Background: The National Health & Morbidity Survey (NHMS) IV (2011) observed that the prevalence of obese children aged less than 18 years in Malaysia is 6.1% compared to 5.4% overweight and obese in NHMS III (2006). As such, this observation is of public health importance as obesity is a forewarning risk factor for chronic diseases such as type-2 diabetes, cardiovascular diseases (CVD) and certain types of cancers. This MyHeART (Malaysian Health and Adolescents longitudinal Research Team) study aims to examine risk factors of non-communicable diseases (NCD) among adolescents.

Research paper thumbnail of Association between self-reported physical activity and indicators of body composition in Malaysian adolescents

Preventive Medicine, 2014

Obesity and lack of physical activity are fast becoming a concern among Malaysian adolescents. Th... more Obesity and lack of physical activity are fast becoming a concern among Malaysian adolescents. This study aims to assess physical activity levels among Malaysian adolescents and investigate the association between physical activity levels and body composition such as body mass index (BMI), waist circumference (WC) and percentage of body fat. 1361 school-going 13 year old multi-ethnic adolescents from population representative samples in Malaysia were involved in our study. Self-reported physical activity levels were assessed using the validated Malay version of the Physical Activity Questionnaire for Older Children (PAQ-C). Height, weight, body fat composition and waist circumference (WC) were measured. Data collection period was from March to May 2012. 10.8% of the males and 7.4% of the females were obese according to the International Obesity Task Force standards. A majority of the adolescents (63.9%) were physically inactive. There is a weak but significant correlation between physical activity scores and the indicators of obesity. The adjusted coefficient for body fatness was relatively more closely correlated to physical activity scores followed by waist circumference and lastly BMI. This study demonstrates that high physical activity scores were associated with the decreased precursor risk factors of obesity.

Research paper thumbnail of Fitness level and body composition indices: cross-sectional study among Malaysian adolescent

BMC Public Health, 2014

The importance of fitness level on the well-being of children and adolescent has long been recogn... more The importance of fitness level on the well-being of children and adolescent has long been recognised. The aim of this study was to investigate the fitness level of school-going Malaysian adolescent, and its association with body composition indices. Methods: 1071 healthy secondary school students participated in the fitness assessment for the Malaysian Health and Adolescents Longitudinal Research Team (MyHEART) study. Body composition indices such as body mass index for age, waist circumference and waist height ratio were measured. Fitness level was assessed with Modified Harvard Step Test. Physical Fitness Score was calculated using total time of step test exercise and resting heart rates. Fitness levels were divided into 3 categories -unacceptable, marginally acceptable, and acceptable. Partial correlation analysis was used to determine the association between fitness score and body composition, by controlling age, gender, locality, ethnicity, smoking status and sexual maturation. Multiple regression analysis was conducted to determine which body composition was the strongest predictor for fitness. Results: 43.3% of the participants were categorised into the unacceptable fitness group, 47.1% were considered marginally acceptable, and 9.6% were acceptable. There was a significant moderate inverse association (p < 0.001) between body composition with fitness score (r = -0.360, -0.413 and -0.403 for body mass index for age, waist circumference and waist height ratio, respectively). Waist circumference was the strongest and significant predictor for fitness (ß = -0.318, p = 0.002). Conclusion: Only 9.6% of the students were fit. There was also an inverse association between body composition and fitness score among apparently healthy adolescents, with waist circumference indicated as the strongest predictor. The low fitness level among the Malaysian adolescent should necessitate the value of healthy lifestyle starting at a young age.

Research paper thumbnail of Metabolic syndrome among 13 year old adolescents: prevalence and risk factors

BMC Public Health, 2014

Background: Obesity and metabolic syndrome is prevalent among Malaysian adolescents and has been ... more Background: Obesity and metabolic syndrome is prevalent among Malaysian adolescents and has been associated with certain behavioural factors such as duration of sleep, screen time and physical activity. The aim of the study is to report the prevalence of overweight/obesity, metabolic syndrome and its risk factors among adolescents. Methods: A multi-staged cluster sampling method was used to select participants from urban and rural schools in Selangor, Perak and Wilayah Persekutuan Kuala Lumpur. Participants underwent anthropometric measurement and physical examination including blood pressure measurement. Blood samples were taken for fasting glucose and lipids and participants answered a self-administered questionnaire. Overweight and obesity was defined using the extrapolated adult body mass index (BMI) cut-offs of >25 kg/m 2 and >30 kg/m 2 , according to the International Obesity Task Force (IOTF) criteria. Metabolic syndrome was defined based on International Diabetes Federation (IDF) 2007 criteria.

Research paper thumbnail of The effectiveness of a life style modification and peer support home blood pressure monitoring in control of hypertension: protocol for a cluster randomized controlled trial

BMC public health, 2014

Death rates due to hypertension in low and middle income countries are higher compared to high in... more Death rates due to hypertension in low and middle income countries are higher compared to high income countries. The present study is designed to combine life style modification and home blood pressure monitoring for control of hypertension in the context of low and middle income countries. The study is a two armed, parallel group, un-blinded, cluster randomized controlled trial undertaken within lower income areas in Kuala Lumpur. Two housing complexes will be assigned to the intervention group and the other two housing complexes will be allocated in the control group. Based on power analysis, 320 participants will be recruited. The participants in the intervention group (n = 160) will undergo three main components in the intervention which are the peer support for home blood pressure monitoring, face to face health coaching on healthy diet and demonstration and training for indoor home based exercise activities while the control group will receive a pamphlet containing information...

Research paper thumbnail of Intakes of Dietary Folate and Other B Vitamins Are Associated with Risks of Esophageal Adenocarcinoma, Barrett's Esophagus, and Reflux Esophagitis

Journal of Nutrition, 2013

Folate is implicated in carcinogenesis via effects on DNA synthesis, repair, and methylation. Eff... more Folate is implicated in carcinogenesis via effects on DNA synthesis, repair, and methylation. Efficient folate metabolism requires other B vitamins and is adversely affected by smoking and alcohol. Esophageal adenocarcinoma (EAC) may develop through a process involving inflammation [reflux esophagitis (RE)] leading to metaplasia [Barrett&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s esophagus (BE)] and carcinoma. Within a population-based, case-control study, we investigated associations between dietary folate and related factors and risks of EAC, BE, and RE. EAC and BE cases had histologically confirmed disease; RE cases had endoscopically visible inflammation. Controls, age-sex frequency matched to EAC cases, were selected through population and general practice registers. Participants underwent structured interviews and completed food-frequency questionnaires. Multivariate ORs and 95% CIs were computed using logistic regression. A total of 256 controls and 223 EAC, 220 BE, and 219 RE cases participated. EAC risk decreased with increasing folate intake (OR highest vs. lowest = 0.56; 95% CI: 0.31, 1.00; P-trend &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01). Similar trends were found for BE (P-trend &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01) and RE (P-trend = 0.01). Vitamin B-6 intake was significantly inversely related to risks of all 3 lesions. Riboflavin intake was inversely associated with RE. Vitamin B-12 intake was positively associated with EAC. For EAC, there was a borderline significant interaction between folate intake and smoking (P-interaction = 0.053); compared with nonsmokers with high (≥ median) folate intake, current smokers with low intakes (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;median) had an 8-fold increased risk (OR: 8.15; 95% CI: 3.61, 18.40). The same group had increased BE risk (OR: 2.93; 95% CI: 1.24, 6.92; P-interaction = 0.12). Folate and other dietary methyl-group factors are implicated in the etiology of EAC and its precursors.

Research paper thumbnail of A longitudinal study through adolescence to adulthood

Public Health, 2002

The Young Hearts (YH) Project is an ongoing study of biological and behavioural risk factors for ... more The Young Hearts (YH) Project is an ongoing study of biological and behavioural risk factors for cardiovascular disease in a representative sample of young people from Northern Ireland, a region of high coronary mortality. This article describes the cross-sectional clinical, dietary and lifestyle data obtained from individuals (aged 20-25 y) who participated in phase 3 of the project (YH3). A total of 489 individuals (251 males, 238 females) participated in YH3 (48.2% response rate). Some 31.1% of participants at YH3 were overweight (BMI &amp;amp;amp;amp;amp;amp;gt;25 kg/m(2)) with 4.4% of males and 8.0% of females were obese (BMI &amp;amp;amp;amp;amp;amp;gt;30 kg/m(2)). More females than males had a very poor fitness (55.0 vs 22.1%, chi-squared 51.70, d.f. 1, P&amp;amp;amp;amp;amp;amp;lt;0.001) and did not participate in any sporting or exercise activity (38.4 vs 24.9%, chi-squared 10.26, d.f. 1, P=0.001). Over 20% of participants had a raised total serum cholesterol (&amp;amp;amp;amp;amp;amp;gt;5.2 mmol/l). More females had a raised serum LDL-cholesterol (&amp;amp;amp;amp;amp;amp;gt;3.0 mmol/l) than males (44.6 vs 34.6%, chi-squared 4.39, d.f. 1, P&amp;amp;amp;amp;amp;amp;lt;0.05). Over 46% of participants reported energy intakes from fat above recommended levels, and 68.5% of participants had saturated fat intakes above those recommended (Dietary reference values for food energy and nutrients for the United Kingdom. HMSO: London, 1991). Just over half of the study population reported alcohol intakes in excess of recommended sensible limits set by the Royal College of Physicians (A great and growing evil: the medical consequences of alcohol abuse. Tavistock: London, 1987), with 36.7% of males and 13.4% of females reporting intakes over twice these recommended limits. A total of 37% of the study population smoked. During young adulthood, individuals may be less amenable to attend a health-related study and recruitment of participants to the current phase of the study proved a major problem. However, these data constitute a unique developmental record from adolescence to young adulthood in a cohort from Northern Ireland and provide additional information on the impact of early life, childhood and young adulthood on the development of risk for chronic disease.

Research paper thumbnail of The Correlates of Body Composition with Heart Rate Recovery after Step Test: An Exploratory Study of Malaysian Adolescents

PLoS ONE, 2013

In adults, heart rate recovery is a predictor of mortality, while in adolescents it is associated... more In adults, heart rate recovery is a predictor of mortality, while in adolescents it is associated with cardio-metabolic risk factors. The aim of this study was to examine the relationship between body composition measures and heart rate recovery (HRR) after step test in Malaysian secondary school students.

Research paper thumbnail of A genome-wide association study identifies new susceptibility loci for non-cardia gastric cancer at 3q13.31 and 5p13.1

Research paper thumbnail of A map of human genome variation from population-scale sequencing

Nature, 2011

The 1000 Genomes Project aims to provide a deep characterization of human genome sequence variati... more The 1000 Genomes Project aims to provide a deep characterization of human genome sequence variation as a foundation for investigating the relationship between genotype and phenotype. Here we present results of the pilot phase of the project, designed to develop and compare different strategies for genome-wide sequencing with high-throughput platforms. We undertook three projects: low-coverage whole-genome sequencing of 179 individuals from four populations; high-coverage sequencing of two mother-father-child trios; and exon-targeted sequencing of 697 individuals from seven populations. We describe the location, allele frequency and local haplotype structure of approximately 15 million single nucleotide polymorphisms, 1 million short insertions and deletions, and 20,000 structural variants, most of which were previously undescribed. We show that, because we have catalogued the vast majority of common variation, over 95% of the currently accessible variants found in any individual are present in this data set. On average, each person is found to carry approximately 250 to 300 loss-of-function variants in annotated genes and 50 to 100 variants previously implicated in inherited disorders. We demonstrate how these results can be used to inform association and functional studies. From the two trios, we directly estimate the rate of de novo germline base substitution mutations to be approximately 10 28 per base pair per generation. We explore the data with regard to signatures of natural selection, and identify a marked reduction of genetic variation in the neighbourhood of genes, due to selection at linked sites. These methods and public data will support the next phase of human genetic research.