Clare Frobisher - Academia.edu (original) (raw)

Papers by Clare Frobisher

Research paper thumbnail of Reproducibility measures and their effect on diet-cancer associations in the Boyd Orr cohort

Journal of Epidemiology and Community Health, May 1, 2007

To quantify measurement error in the estimation of family diet intakes using 7-day household food... more To quantify measurement error in the estimation of family diet intakes using 7-day household food inventories and to investigate the effect of measurement-error adjustment on diet-disease associations. Historical cohort study in 16 districts in England and Scotland, between 1937 and 1939. 4999 children from 1352 families in the Carnegie Survey of Diet and Health. 86.6% of these children were traced as adults and form the Boyd Orr cohort. The reproducibility analysis was based on 195 families with two assessments of family diet recorded 3-15 months apart. Intraclass correlation coefficients (ICCs) were calculated for a variety of nutrients and food groups. Diet-cancer associations reported previously in the Boyd Orr cohort were reassessed using two methods: (a) the ICC and (b) the regression calibration. The ICCs for the dietary intakes ranged from 0.44 (beta carotene) to 0.85 (milk and milk products). The crude fully adjusted hazard ratio (HR) for cancer mortality per 1 MJ/day increase in energy intake was 1.15 (95% CI 1.06 to 1.24). After adjustment using the ICC for energy (0.80) the HR (95% CI) increased to 1.19 (1.08 to 1.31), and the estimate from regression calibration was 1.14 (0.98 to 1.32). The crude fully adjusted odds ratio (OR) for cancer incidence per 40 g/day increase in fruit intake was 0.84 (95% CI 0.73 to 0.97). After adjustment using the fruit ICC (0.78) it became 0.81 (0.67 to 0.96) and the OR derived from regression calibration was 0.81 (0.59 to 1.10). The diet-disease relationships for the dietary intakes with low measurement error were robust to adjustment for measurement error.

Research paper thumbnail of Long-term adverse outcomes in survivors of childhood bone sarcoma: the British Childhood Cancer Survivor Study

British journal of cancer, Jan 9, 2015

With improved survival, more bone sarcoma survivors are approaching middle age making it crucial ... more With improved survival, more bone sarcoma survivors are approaching middle age making it crucial to investigate the late effects of their cancer and its treatment. We investigated the long-term risks of adverse outcomes among 5-year bone sarcoma survivors within the British Childhood Cancer Survivor Study. Cause-specific mortality and risk of subsequent primary neoplasms (SPNs) were investigated for 664 bone sarcoma survivors. Use of health services, health and marital status, alcohol and smoking habits, and educational qualifications were investigated for survivors who completed a questionnaire. Survivors were seven times more likely to experience all-cause mortality than expected, and there were substantial differences in risk depending on tumour type. Beyond 25 years follow-up the risk of dying from all-causes was comparable to the general population. This is in contrast to dying before 25 years where the risk was 12.7-fold that expected. Survivors were also four times more likel...

Research paper thumbnail of Aspects of mental health dysfunction among survivors of childhood cancer

British journal of cancer, Jan 29, 2015

Some previous studies have reported that survivors of childhood cancer are at an increased risk o... more Some previous studies have reported that survivors of childhood cancer are at an increased risk of developing long-term mental health morbidity, whilst others have reported that this is not the case. Therefore, we analysed 5-year survivors of childhood cancer using the British Childhood Cancer Survivor Study (BCCSS) to determine the risks of aspects of long-term mental health dysfunction. Within the BCCSS, 10 488 survivors completed a questionnaire that ascertained mental health-related information via 10 questions from the Short Form-36 survey. Internal analyses were conducted using multivariable logistic regression to determine risk factors for mental health dysfunction. External analyses were undertaken using direct standardisation to compare mental health dysfunction in survivors with UK norms. This study has shown that overall, childhood cancer survivors had a significantly higher prevalence of mental health dysfunction for 6/10 questions analysed compared to UK norms. Central ...

Research paper thumbnail of Childhood dairy intake and adult cancer risk: 65-y follow-up of the Boyd Orr cohort

The American journal of clinical nutrition, 2007

Dairy consumption affects biological pathways associated with carcinogenesis. Evidence for a link... more Dairy consumption affects biological pathways associated with carcinogenesis. Evidence for a link between cancer risk and dairy consumption in adulthood is increasing, but associations with childhood dairy consumption have not been studied adequately. We investigated whether dairy consumption in childhood is associated with cancer incidence and mortality in adulthood. From 1937 through 1939, some 4,999 children living in England and Scotland participated in a study of family food consumption, assessed from 7-d household food inventories. The National Health Service central register was used to ascertain cancer registrations and deaths between 1948 and 2005 in the 4,383 traced cohort members. Per capita household intake estimates for dairy products and calcium were used as proxy for individual intake. During the follow-up period, 770 cancer registrations or cancer deaths occurred. High childhood total dairy intake was associated with a near-tripling in the odds of colorectal cancer [...

Research paper thumbnail of The British Childhood Cancer Survivor Study: Objectives, methods, population structure, response rates and initial descriptive information

Pediatric Blood & Cancer, 2008

In Britain 75% of individuals diagnosed with childhood cancer survive at least 5 years. The Briti... more In Britain 75% of individuals diagnosed with childhood cancer survive at least 5 years. The British Childhood Cancer Survivor Study was established to determine the risks of adverse health and social outcomes among survivors. To be eligible individuals were diagnosed with childhood cancer in Britain between 1940 and 1991 and survived at least 5 years. The entire cohort of 17,981 form the basis of population-based studies of late mortality and the risks/causes of second malignant neoplasms using national registration systems. A postal questionnaire was sent to survivors who were alive and aged at least 16 years via their primary care physician. Of the 14,836 survivors eligible to receive a questionnaire, 10,483 (71%) returned it completed. Of the 13,211 who were mailed a questionnaire by their primary care physician 10,483 (79%) returned it completed. Outline treatment information concerning initial radiotherapy, chemotherapy and surgery is available. This is the largest available population-based cohort of childhood cancer survivors to have included investigation of a wide spectrum of adverse outcomes (the risk of which might be increased as a result of childhood cancer or its treatment). The study should provide useful information for counselling survivors, planning long-term clinical follow-up and evaluating the long-term risks likely to be associated with proposed treatment strategies.

Research paper thumbnail of RISK OF BLADDER CANCER AFTER CHILDHOOD CANCER

The Journal of Urology, 2008

... Risk of bladder cancer after childhood cancer. Gurung, PM and Frobisher, C and Leiper, A and ... more ... Risk of bladder cancer after childhood cancer. Gurung, PM and Frobisher, C and Leiper, A and Woodhouse, CRJ and Hawkins, MM (2008) Risk of bladder cancer after childhood cancer. In: JOURNAL OF UROLOGY. ,ELSEVIER SCIENCE INC, 322 - 322. ...

Research paper thumbnail of Educational Attainment Among Adult Survivors of Childhood Cancer in Great Britain: A Population-Based Cohort Study

JNCI Journal of the National Cancer Institute, 2010

Childhood cancer survivors had lower educational attainment than the general population (degree: ... more Childhood cancer survivors had lower educational attainment than the general population (degree: odds ratio [OR] = 0.77, 99% confidence interval [CI] = 0.68 to 0.87; teaching qualification: OR = 0.85, 99% CI = 0.77 to 0.94; A'level: OR = 0.85, 99% CI = 0.78 to 0.93; O'level: OR = 0.81, 99% CI = 0.74 to 0.90; P < .001, all levels). Statistically significant deficits were restricted to central nervous system (CNS) neoplasm and leukemia survivors. For leukemia, only those treated with radiotherapy were considered. Odds ratios for achievement by irradiated CNS tumor survivors were 50%-74% of those for cranially irradiated leukemia or nonirradiated CNS tumor survivors. Survivors at greater risk of poorer educational outcomes included those treated with cranial irradiation, diagnosed with a CNS tumor, older at questionnaire completion, younger at diagnosis, diagnosed with epilepsy, and who were female.

Research paper thumbnail of The estimation of food portion sizes: a comparison between using descriptions of portion sizes and a photographic food atlas by children and adults

Journal of Human Nutrition and Dietetics, 2003

Food Photographs and standard portion sizes have been used with adults to assess portion size whe... more Food Photographs and standard portion sizes have been used with adults to assess portion size when recording dietary intake. The effectiveness of these methods may be reduced when memory/recall is required and children may have problems using these techniques. Adults (47) and children (37) were recruited from amongst university personnel, their children and children&#39;s friends to assess portion sizes of nine self-served amounts of selected food items using food photographs and standard descriptions of portion sizes. Portion sizes were estimated directly after self-serving and three - 4 days later. Substantial differences in the estimate of portion sizes were observed for most foods regardless of the method used or the age of the subjects, median difference range: -52-100%. For children there were greater errors using both methods than for adults. Significant differences were found between the two methods of estimating weight. The food atlas provided higher median estimated weights for the majority of the food items. There were very few differences in the estimation of portion sizes between the two testing periods. The findings would suggest that either an alternative method or a modification of the methods used here for estimating portion sizes in young subjects, for example standard food portion sizes for children of different ages such as those that are being developed by the Food Standards Agency, would be more appropriate.

Research paper thumbnail of Reproducibility measures and their effect on diet-cancer associations in the Boyd Orr cohort

Journal of Epidemiology & Community Health, 2007

To quantify measurement error in the estimation of family diet intakes using 7-day household food... more To quantify measurement error in the estimation of family diet intakes using 7-day household food inventories and to investigate the effect of measurement-error adjustment on diet-disease associations. Historical cohort study in 16 districts in England and Scotland, between 1937 and 1939. 4999 children from 1352 families in the Carnegie Survey of Diet and Health. 86.6% of these children were traced as adults and form the Boyd Orr cohort. The reproducibility analysis was based on 195 families with two assessments of family diet recorded 3-15 months apart. Intraclass correlation coefficients (ICCs) were calculated for a variety of nutrients and food groups. Diet-cancer associations reported previously in the Boyd Orr cohort were reassessed using two methods: (a) the ICC and (b) the regression calibration. The ICCs for the dietary intakes ranged from 0.44 (beta carotene) to 0.85 (milk and milk products). The crude fully adjusted hazard ratio (HR) for cancer mortality per 1 MJ/day increase in energy intake was 1.15 (95% CI 1.06 to 1.24). After adjustment using the ICC for energy (0.80) the HR (95% CI) increased to 1.19 (1.08 to 1.31), and the estimate from regression calibration was 1.14 (0.98 to 1.32). The crude fully adjusted odds ratio (OR) for cancer incidence per 40 g/day increase in fruit intake was 0.84 (95% CI 0.73 to 0.97). After adjustment using the fruit ICC (0.78) it became 0.81 (0.67 to 0.96) and the OR derived from regression calibration was 0.81 (0.59 to 1.10). The diet-disease relationships for the dietary intakes with low measurement error were robust to adjustment for measurement error.

Research paper thumbnail of Population-Based Risks of CNS Tumors in Survivors of Childhood Cancer: The British Childhood Cancer Survivor Study

Journal of Clinical Oncology, 2010

CNS tumors are the most common second primary neoplasm (SPN) observed after childhood cancer in B... more CNS tumors are the most common second primary neoplasm (SPN) observed after childhood cancer in Britain, but the relationship of risk to doses of previous radiotherapy and chemotherapy is uncertain. The British Childhood Cancer Survivor Study is a national, population-based, cohort study of 17,980 individuals surviving at least 5 years after diagnosis of childhood cancer. Linkage to national, population-based cancer registries identified 247 SPNs of the CNS. Cohort and nested case-control studies were undertaken. There were 137 meningiomas, 73 gliomas, and 37 other CNS neoplasms included in the analysis. The risk of meningioma increased strongly, linearly, and independently with each of dose of radiation to meningeal tissue and dose of intrathecal methotrexate. Those whose meningeal tissue received 0.01 to 9.99, 10.00 to 19.99, 20.00 to 29.99, 30.00 to 39.99 and≥40 Gy had risks that were two-fold, eight-fold, 52-fold, 568-fold, and 479-fold, respectively, the risks experienced by those whose meningeal tissue was unexposed. The risk of meningioma among individuals receiving 1 to 39,40 to 69, and at least 70 mg/m2 of intrathecal methotrexate was 15-fold, 11-fold, and 36-fold, respectively, the risk experienced by those unexposed. The standardized incidence ratio for gliomas was 10.8 (95% CI, 8.5 to 13.6). The risk of glioma/primitive neuroectodermal tumors increased linearly with dose of radiation, and those who had CNS tissue exposed to at least 40 Gy experienced a risk four-fold that experienced by those who had CNS tissue unexposed. The largest-ever study, to our knowledge, of CNS tumors in survivors of childhood cancer indicates that the risk of meningioma increases rapidly with increased dose of radiation to meningeal tissue and with increased dose of intrathecal methotrexate.

Research paper thumbnail of Health Care Use of Long-Term Survivors of Childhood Cancer: The British Childhood Cancer Survivor Study

Journal of Clinical Oncology, 2011

Survivors of childhood cancer are at high risk of chronic conditions, but few studies investigate... more Survivors of childhood cancer are at high risk of chronic conditions, but few studies investigated whether this translates into increased health care utilization. We compared health care service utilization between childhood cancer survivors and the general British population and investigated potential risk factors.

Research paper thumbnail of Survival After Second Primary Neoplasms of the Brain or Spinal Cord in Survivors of Childhood Cancer: Results From the British Childhood Cancer Survivor Study

Journal of Clinical Oncology, 2009

Survival after brain or spinal cord neoplasms is poor and varies by diagnostic group, age, grade,... more Survival after brain or spinal cord neoplasms is poor and varies by diagnostic group, age, grade, treatment and pretreatment factors, and location and size of tumor. We carried out a study to investigate survival and factors affecting survival of all diagnostic types of second primary brain or spinal cord neoplasms.

Research paper thumbnail of Long-term Cause-Specific Mortality Among Survivors of Childhood Cancer

JAMA, 2010

Context Survivors of childhood cancer are at increased risk of premature mortality compared with ... more Context Survivors of childhood cancer are at increased risk of premature mortality compared with the general population, but little is known about the long-term risks of specific causes of death, particularly beyond 25 years from diagnosis at ages when background mortality in the general population starts to increase substantially.

Research paper thumbnail of Long-term Risks of Subsequent Primary Neoplasms Among Survivors of Childhood Cancer

JAMA, 2011

Context Survivors of childhood cancer are at excess risk of developing subsequent primary neoplas... more Context Survivors of childhood cancer are at excess risk of developing subsequent primary neoplasms but the long-term risks are uncertain.

Research paper thumbnail of Second primary neoplasms in survivors of Wilms' tumour-A population-based cohort study from the British Childhood Cancer Survivor Study

International Journal of Cancer, 2008

A British population-based cohort study was carried out to determine the risk of second primary n... more A British population-based cohort study was carried out to determine the risk of second primary neoplasms in survivors of Wilms&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;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; tumour. The cohort was obtained from the British Childhood Cancer Survivor Study, a population-based cohort study of treatment toxicities in 18,044 individuals diagnosed with childhood cancer, at an age of less than 15 years, between 1940 and 1991 in Britain. There were 1,441 Wilms&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;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; tumour survivors in the cohort: 732 males (50.8%) and 709 females (49.2%). Total follow-up from 5-year survival was 27,841 person years, mean follow-up of 19.3 years per survivor. There were 81 second primary neoplasms, including 52 solid neoplasms, 3 acute myeloid leukaemias and 26 basal cell carcinomas. Thirty-five of the 39 solid neoplasms that developed in the thoracic, abdominal or pelvic region occurred within irradiated tissue. The standardised incidence ratio for all solid second primary neoplasms was 6.7 (95% CI: 5.0-8.8). Cumulative incidence for all solid second primary neoplasms by ages 30, 40 and 50 years was 2.3% (1.4-3.5%), 6.8% (4.6-9.5%) and 12.2% (7.3-18.4%). The overall risk of second primary neoplasms in survivors of Wilms&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;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; tumour treated between 1940 and 1991 was substantial, and solid second tumours tended to develop in the irradiated tissue. Continued follow-up of these survivors is important to monitor such late effects of treatment. It is also important to evaluate the risk of second primary neoplasms following more recent lower radiation dose treatment practices.

Research paper thumbnail of Hypothyroidism following childhood cancer therapy-an under diagnosed complication

International Journal of Cancer, 2012

To determine the prevalence of hypothyroidism amongst most adult survivors of childhood cancer in... more To determine the prevalence of hypothyroidism amongst most adult survivors of childhood cancer in Britain using the British Childhood Cancer Survivor Study (BCCSS). The BCCSS is a population based cohort of individuals diagnosed with childhood cancer between 1940 and 1991 and who survived at least 5 years from diagnosis (n 5 17,981). 10483, 71% of those survivors aged at least 16 years, returned a completed questionnaire, which asked if hypothyroidism had been diagnosed. Of the whole cohort, 7.7% reported hypothyroidism with the highest risk among patients treated for Hodgkin's disease (HD) (19.9%), CNS neoplasms (15.3%), Non-Hodgkin's lymphoma (6.2%) and leukaemia (5.2%). Survivors were more likely to develop hypothyroidism if they had received radiotherapy for HD (p 5 0.0001) or a CNS neoplasm (p < 0.00005) but not leukaemia (p 5 0.3). In these three patient groups, the frequency of hypothyroidism was similar in men and women. Survivors of irradiated CNS tumours reported a prevalence of hypothyroidism, which was substantially lower if discharged to primary care compared with being on hospital follow-up and which declined substantially with increased follow-up in both primary care (p 5 0.004) and hospital follow-up (p 5 0.023) settings. Hypothyroidism is a common finding amongst adult survivors of childhood malignancy. The substantial differences in reported hypothyroidism prevalence after irradiated CNS neoplasms suggests substantial under-diagnosis, which increased with increased follow-up, and which increased among those followed-up in primary care compared with hospital settings.

Research paper thumbnail of Long-term population-based risks of breast cancer after childhood cancer

International Journal of Cancer, 2008

Previous studies have reported substantially increased risks of breast cancer among survivors of ... more Previous studies have reported substantially increased risks of breast cancer among survivors of childhood cancer at 10-20 years posttreatment. Whether these excess risks are sustained beyond 40 years of age when general population incidence of breast cancer begins its steep increase is largely unknown. We quantified the risk of breast cancer in adult female survivors with considerably more survivors followed-up beyond 40 years of age than previously available. Standardized Incidence Ratios (SIR), Excess Absolute Risks (EAR), and cumulative incidence were calculated within a population-based cohort of 8,093 female survivors of childhood cancer. Poisson regression models were used to model SIRs and EARs in a multivariable setting. Eighty-one survivors developed a primary breast cancer, where 37.5 were expected (SIR5 2.2, 95% CI: 1.7-2.7). SIRs decreased significantly with increasing attained age (p trend < 0.001) to an SIR of 0.9 (95% CI: 0.5-1.8) at ages beyond 50 years; EARs increased significantly to about 40 years of age (p trend < 0.001) but then plateau. Between 30 and 49 years of age survivors experienced approximately 1 extra breast cancer per 1,000 survivors per year. Overall, 3% developed breast cancer by the age of 50. The substantially increased relative risks of breast cancer observed at 10-20 years postdiagnosis are not sustained into ages at which the risk of breast cancer in the general population becomes substantial. Among women who survived to an age of at least 50 years there is currently no evidence of an increased risk of breast cancer.

Research paper thumbnail of Diet in childhood and adult cardiovascular and all cause mortality: the Boyd Orr cohort

Heart, 2005

Objective: To examine the association between childhood diet and cardiovascular mortality. Design... more Objective: To examine the association between childhood diet and cardiovascular mortality. Design: Historical cohort study. Setting: 16 centres in England and Scotland. Participants: 4028 people (from 1234 families) who took part in Boyd Orr's survey of family diet and health in Britain between 1937 and 1939 followed up through the National Health Service central register.

Research paper thumbnail of Pregnancy Outcomes among Adult Survivors of Childhood Cancer in the British Childhood Cancer Survivor Study

Cancer Epidemiology Biomarkers & Prevention, 2009

We used data from the first large-scale overwhelmingly population-based study (a) to quantify the... more We used data from the first large-scale overwhelmingly population-based study (a) to quantify the risk of adverse pregnancy outcomes in survivors of childhood cancer in relation to cancer type and treatment and (b) to assess live birth rates relative to the general population. A questionnaire, including questions inquiring about pregnancy outcomes, was completed by 10,483 survivors. A total of 7,300 pregnancies were reported. Odds ratios (OR) for live birth, miscarriage, termination, stillbirth, premature birth, and low birth weight were calculated for different types of childhood cancer and by whether initial treatment involved chemotherapy and abdominal or brain irradiation. For females, the observed number of live births was compared with that expected based on the general population of England and Wales. Female survivors exposed to abdominal irradiation had a significantly increased OR of delivering preterm [OR, 3.2; 95% confidence interval (95% CI), 2.1-4.7] and producing offspring with a low birth weight (OR, 1.9; 95% CI, 1.1-3.2). An increased OR of miscarriage was also associated with abdominal radiotherapy (OR, 1.4; 95% CI, 1.0-1.9). The number of live births observed from all female survivors was two thirds of that expected (O/E, 0.64; 95% CI, 0.62-0.66) and lowest among survivors treated with brain (O/E, 0.52; 95% CI, 0.48-0.56) and abdominal radiotherapy (O/E, 0.55; 95% CI, 0.50-0.61). Female survivors of childhood cancer treated with abdominal radiotherapy are at 3-fold increased risk of delivering preterm, 2-fold increased risk of low birth weight, and a small increased risk of miscarriage. Overall, female survivors produce considerably fewer offspring than expected, particularly those treated with abdominal or brain radiotherapy.

Research paper thumbnail of Extent of Alcohol Consumption among Adult Survivors of Childhood Cancer: The British Childhood Cancer Survivor Study

Cancer Epidemiology Biomarkers & Prevention, 2010

Background: This study aimed to identify subgroups of childhood cancer survivors at highest risk ... more Background: This study aimed to identify subgroups of childhood cancer survivors at highest risk of consuming alcohol, consuming above recommended weekly levels, and consuming potentially harmful amounts and compare survivor risks with those expected from the general population.

Research paper thumbnail of Reproducibility measures and their effect on diet-cancer associations in the Boyd Orr cohort

Journal of Epidemiology and Community Health, May 1, 2007

To quantify measurement error in the estimation of family diet intakes using 7-day household food... more To quantify measurement error in the estimation of family diet intakes using 7-day household food inventories and to investigate the effect of measurement-error adjustment on diet-disease associations. Historical cohort study in 16 districts in England and Scotland, between 1937 and 1939. 4999 children from 1352 families in the Carnegie Survey of Diet and Health. 86.6% of these children were traced as adults and form the Boyd Orr cohort. The reproducibility analysis was based on 195 families with two assessments of family diet recorded 3-15 months apart. Intraclass correlation coefficients (ICCs) were calculated for a variety of nutrients and food groups. Diet-cancer associations reported previously in the Boyd Orr cohort were reassessed using two methods: (a) the ICC and (b) the regression calibration. The ICCs for the dietary intakes ranged from 0.44 (beta carotene) to 0.85 (milk and milk products). The crude fully adjusted hazard ratio (HR) for cancer mortality per 1 MJ/day increase in energy intake was 1.15 (95% CI 1.06 to 1.24). After adjustment using the ICC for energy (0.80) the HR (95% CI) increased to 1.19 (1.08 to 1.31), and the estimate from regression calibration was 1.14 (0.98 to 1.32). The crude fully adjusted odds ratio (OR) for cancer incidence per 40 g/day increase in fruit intake was 0.84 (95% CI 0.73 to 0.97). After adjustment using the fruit ICC (0.78) it became 0.81 (0.67 to 0.96) and the OR derived from regression calibration was 0.81 (0.59 to 1.10). The diet-disease relationships for the dietary intakes with low measurement error were robust to adjustment for measurement error.

Research paper thumbnail of Long-term adverse outcomes in survivors of childhood bone sarcoma: the British Childhood Cancer Survivor Study

British journal of cancer, Jan 9, 2015

With improved survival, more bone sarcoma survivors are approaching middle age making it crucial ... more With improved survival, more bone sarcoma survivors are approaching middle age making it crucial to investigate the late effects of their cancer and its treatment. We investigated the long-term risks of adverse outcomes among 5-year bone sarcoma survivors within the British Childhood Cancer Survivor Study. Cause-specific mortality and risk of subsequent primary neoplasms (SPNs) were investigated for 664 bone sarcoma survivors. Use of health services, health and marital status, alcohol and smoking habits, and educational qualifications were investigated for survivors who completed a questionnaire. Survivors were seven times more likely to experience all-cause mortality than expected, and there were substantial differences in risk depending on tumour type. Beyond 25 years follow-up the risk of dying from all-causes was comparable to the general population. This is in contrast to dying before 25 years where the risk was 12.7-fold that expected. Survivors were also four times more likel...

Research paper thumbnail of Aspects of mental health dysfunction among survivors of childhood cancer

British journal of cancer, Jan 29, 2015

Some previous studies have reported that survivors of childhood cancer are at an increased risk o... more Some previous studies have reported that survivors of childhood cancer are at an increased risk of developing long-term mental health morbidity, whilst others have reported that this is not the case. Therefore, we analysed 5-year survivors of childhood cancer using the British Childhood Cancer Survivor Study (BCCSS) to determine the risks of aspects of long-term mental health dysfunction. Within the BCCSS, 10 488 survivors completed a questionnaire that ascertained mental health-related information via 10 questions from the Short Form-36 survey. Internal analyses were conducted using multivariable logistic regression to determine risk factors for mental health dysfunction. External analyses were undertaken using direct standardisation to compare mental health dysfunction in survivors with UK norms. This study has shown that overall, childhood cancer survivors had a significantly higher prevalence of mental health dysfunction for 6/10 questions analysed compared to UK norms. Central ...

Research paper thumbnail of Childhood dairy intake and adult cancer risk: 65-y follow-up of the Boyd Orr cohort

The American journal of clinical nutrition, 2007

Dairy consumption affects biological pathways associated with carcinogenesis. Evidence for a link... more Dairy consumption affects biological pathways associated with carcinogenesis. Evidence for a link between cancer risk and dairy consumption in adulthood is increasing, but associations with childhood dairy consumption have not been studied adequately. We investigated whether dairy consumption in childhood is associated with cancer incidence and mortality in adulthood. From 1937 through 1939, some 4,999 children living in England and Scotland participated in a study of family food consumption, assessed from 7-d household food inventories. The National Health Service central register was used to ascertain cancer registrations and deaths between 1948 and 2005 in the 4,383 traced cohort members. Per capita household intake estimates for dairy products and calcium were used as proxy for individual intake. During the follow-up period, 770 cancer registrations or cancer deaths occurred. High childhood total dairy intake was associated with a near-tripling in the odds of colorectal cancer [...

Research paper thumbnail of The British Childhood Cancer Survivor Study: Objectives, methods, population structure, response rates and initial descriptive information

Pediatric Blood & Cancer, 2008

In Britain 75% of individuals diagnosed with childhood cancer survive at least 5 years. The Briti... more In Britain 75% of individuals diagnosed with childhood cancer survive at least 5 years. The British Childhood Cancer Survivor Study was established to determine the risks of adverse health and social outcomes among survivors. To be eligible individuals were diagnosed with childhood cancer in Britain between 1940 and 1991 and survived at least 5 years. The entire cohort of 17,981 form the basis of population-based studies of late mortality and the risks/causes of second malignant neoplasms using national registration systems. A postal questionnaire was sent to survivors who were alive and aged at least 16 years via their primary care physician. Of the 14,836 survivors eligible to receive a questionnaire, 10,483 (71%) returned it completed. Of the 13,211 who were mailed a questionnaire by their primary care physician 10,483 (79%) returned it completed. Outline treatment information concerning initial radiotherapy, chemotherapy and surgery is available. This is the largest available population-based cohort of childhood cancer survivors to have included investigation of a wide spectrum of adverse outcomes (the risk of which might be increased as a result of childhood cancer or its treatment). The study should provide useful information for counselling survivors, planning long-term clinical follow-up and evaluating the long-term risks likely to be associated with proposed treatment strategies.

Research paper thumbnail of RISK OF BLADDER CANCER AFTER CHILDHOOD CANCER

The Journal of Urology, 2008

... Risk of bladder cancer after childhood cancer. Gurung, PM and Frobisher, C and Leiper, A and ... more ... Risk of bladder cancer after childhood cancer. Gurung, PM and Frobisher, C and Leiper, A and Woodhouse, CRJ and Hawkins, MM (2008) Risk of bladder cancer after childhood cancer. In: JOURNAL OF UROLOGY. ,ELSEVIER SCIENCE INC, 322 - 322. ...

Research paper thumbnail of Educational Attainment Among Adult Survivors of Childhood Cancer in Great Britain: A Population-Based Cohort Study

JNCI Journal of the National Cancer Institute, 2010

Childhood cancer survivors had lower educational attainment than the general population (degree: ... more Childhood cancer survivors had lower educational attainment than the general population (degree: odds ratio [OR] = 0.77, 99% confidence interval [CI] = 0.68 to 0.87; teaching qualification: OR = 0.85, 99% CI = 0.77 to 0.94; A'level: OR = 0.85, 99% CI = 0.78 to 0.93; O'level: OR = 0.81, 99% CI = 0.74 to 0.90; P < .001, all levels). Statistically significant deficits were restricted to central nervous system (CNS) neoplasm and leukemia survivors. For leukemia, only those treated with radiotherapy were considered. Odds ratios for achievement by irradiated CNS tumor survivors were 50%-74% of those for cranially irradiated leukemia or nonirradiated CNS tumor survivors. Survivors at greater risk of poorer educational outcomes included those treated with cranial irradiation, diagnosed with a CNS tumor, older at questionnaire completion, younger at diagnosis, diagnosed with epilepsy, and who were female.

Research paper thumbnail of The estimation of food portion sizes: a comparison between using descriptions of portion sizes and a photographic food atlas by children and adults

Journal of Human Nutrition and Dietetics, 2003

Food Photographs and standard portion sizes have been used with adults to assess portion size whe... more Food Photographs and standard portion sizes have been used with adults to assess portion size when recording dietary intake. The effectiveness of these methods may be reduced when memory/recall is required and children may have problems using these techniques. Adults (47) and children (37) were recruited from amongst university personnel, their children and children&#39;s friends to assess portion sizes of nine self-served amounts of selected food items using food photographs and standard descriptions of portion sizes. Portion sizes were estimated directly after self-serving and three - 4 days later. Substantial differences in the estimate of portion sizes were observed for most foods regardless of the method used or the age of the subjects, median difference range: -52-100%. For children there were greater errors using both methods than for adults. Significant differences were found between the two methods of estimating weight. The food atlas provided higher median estimated weights for the majority of the food items. There were very few differences in the estimation of portion sizes between the two testing periods. The findings would suggest that either an alternative method or a modification of the methods used here for estimating portion sizes in young subjects, for example standard food portion sizes for children of different ages such as those that are being developed by the Food Standards Agency, would be more appropriate.

Research paper thumbnail of Reproducibility measures and their effect on diet-cancer associations in the Boyd Orr cohort

Journal of Epidemiology & Community Health, 2007

To quantify measurement error in the estimation of family diet intakes using 7-day household food... more To quantify measurement error in the estimation of family diet intakes using 7-day household food inventories and to investigate the effect of measurement-error adjustment on diet-disease associations. Historical cohort study in 16 districts in England and Scotland, between 1937 and 1939. 4999 children from 1352 families in the Carnegie Survey of Diet and Health. 86.6% of these children were traced as adults and form the Boyd Orr cohort. The reproducibility analysis was based on 195 families with two assessments of family diet recorded 3-15 months apart. Intraclass correlation coefficients (ICCs) were calculated for a variety of nutrients and food groups. Diet-cancer associations reported previously in the Boyd Orr cohort were reassessed using two methods: (a) the ICC and (b) the regression calibration. The ICCs for the dietary intakes ranged from 0.44 (beta carotene) to 0.85 (milk and milk products). The crude fully adjusted hazard ratio (HR) for cancer mortality per 1 MJ/day increase in energy intake was 1.15 (95% CI 1.06 to 1.24). After adjustment using the ICC for energy (0.80) the HR (95% CI) increased to 1.19 (1.08 to 1.31), and the estimate from regression calibration was 1.14 (0.98 to 1.32). The crude fully adjusted odds ratio (OR) for cancer incidence per 40 g/day increase in fruit intake was 0.84 (95% CI 0.73 to 0.97). After adjustment using the fruit ICC (0.78) it became 0.81 (0.67 to 0.96) and the OR derived from regression calibration was 0.81 (0.59 to 1.10). The diet-disease relationships for the dietary intakes with low measurement error were robust to adjustment for measurement error.

Research paper thumbnail of Population-Based Risks of CNS Tumors in Survivors of Childhood Cancer: The British Childhood Cancer Survivor Study

Journal of Clinical Oncology, 2010

CNS tumors are the most common second primary neoplasm (SPN) observed after childhood cancer in B... more CNS tumors are the most common second primary neoplasm (SPN) observed after childhood cancer in Britain, but the relationship of risk to doses of previous radiotherapy and chemotherapy is uncertain. The British Childhood Cancer Survivor Study is a national, population-based, cohort study of 17,980 individuals surviving at least 5 years after diagnosis of childhood cancer. Linkage to national, population-based cancer registries identified 247 SPNs of the CNS. Cohort and nested case-control studies were undertaken. There were 137 meningiomas, 73 gliomas, and 37 other CNS neoplasms included in the analysis. The risk of meningioma increased strongly, linearly, and independently with each of dose of radiation to meningeal tissue and dose of intrathecal methotrexate. Those whose meningeal tissue received 0.01 to 9.99, 10.00 to 19.99, 20.00 to 29.99, 30.00 to 39.99 and≥40 Gy had risks that were two-fold, eight-fold, 52-fold, 568-fold, and 479-fold, respectively, the risks experienced by those whose meningeal tissue was unexposed. The risk of meningioma among individuals receiving 1 to 39,40 to 69, and at least 70 mg/m2 of intrathecal methotrexate was 15-fold, 11-fold, and 36-fold, respectively, the risk experienced by those unexposed. The standardized incidence ratio for gliomas was 10.8 (95% CI, 8.5 to 13.6). The risk of glioma/primitive neuroectodermal tumors increased linearly with dose of radiation, and those who had CNS tissue exposed to at least 40 Gy experienced a risk four-fold that experienced by those who had CNS tissue unexposed. The largest-ever study, to our knowledge, of CNS tumors in survivors of childhood cancer indicates that the risk of meningioma increases rapidly with increased dose of radiation to meningeal tissue and with increased dose of intrathecal methotrexate.

Research paper thumbnail of Health Care Use of Long-Term Survivors of Childhood Cancer: The British Childhood Cancer Survivor Study

Journal of Clinical Oncology, 2011

Survivors of childhood cancer are at high risk of chronic conditions, but few studies investigate... more Survivors of childhood cancer are at high risk of chronic conditions, but few studies investigated whether this translates into increased health care utilization. We compared health care service utilization between childhood cancer survivors and the general British population and investigated potential risk factors.

Research paper thumbnail of Survival After Second Primary Neoplasms of the Brain or Spinal Cord in Survivors of Childhood Cancer: Results From the British Childhood Cancer Survivor Study

Journal of Clinical Oncology, 2009

Survival after brain or spinal cord neoplasms is poor and varies by diagnostic group, age, grade,... more Survival after brain or spinal cord neoplasms is poor and varies by diagnostic group, age, grade, treatment and pretreatment factors, and location and size of tumor. We carried out a study to investigate survival and factors affecting survival of all diagnostic types of second primary brain or spinal cord neoplasms.

Research paper thumbnail of Long-term Cause-Specific Mortality Among Survivors of Childhood Cancer

JAMA, 2010

Context Survivors of childhood cancer are at increased risk of premature mortality compared with ... more Context Survivors of childhood cancer are at increased risk of premature mortality compared with the general population, but little is known about the long-term risks of specific causes of death, particularly beyond 25 years from diagnosis at ages when background mortality in the general population starts to increase substantially.

Research paper thumbnail of Long-term Risks of Subsequent Primary Neoplasms Among Survivors of Childhood Cancer

JAMA, 2011

Context Survivors of childhood cancer are at excess risk of developing subsequent primary neoplas... more Context Survivors of childhood cancer are at excess risk of developing subsequent primary neoplasms but the long-term risks are uncertain.

Research paper thumbnail of Second primary neoplasms in survivors of Wilms' tumour-A population-based cohort study from the British Childhood Cancer Survivor Study

International Journal of Cancer, 2008

A British population-based cohort study was carried out to determine the risk of second primary n... more A British population-based cohort study was carried out to determine the risk of second primary neoplasms in survivors of Wilms&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;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; tumour. The cohort was obtained from the British Childhood Cancer Survivor Study, a population-based cohort study of treatment toxicities in 18,044 individuals diagnosed with childhood cancer, at an age of less than 15 years, between 1940 and 1991 in Britain. There were 1,441 Wilms&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;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; tumour survivors in the cohort: 732 males (50.8%) and 709 females (49.2%). Total follow-up from 5-year survival was 27,841 person years, mean follow-up of 19.3 years per survivor. There were 81 second primary neoplasms, including 52 solid neoplasms, 3 acute myeloid leukaemias and 26 basal cell carcinomas. Thirty-five of the 39 solid neoplasms that developed in the thoracic, abdominal or pelvic region occurred within irradiated tissue. The standardised incidence ratio for all solid second primary neoplasms was 6.7 (95% CI: 5.0-8.8). Cumulative incidence for all solid second primary neoplasms by ages 30, 40 and 50 years was 2.3% (1.4-3.5%), 6.8% (4.6-9.5%) and 12.2% (7.3-18.4%). The overall risk of second primary neoplasms in survivors of Wilms&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;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; tumour treated between 1940 and 1991 was substantial, and solid second tumours tended to develop in the irradiated tissue. Continued follow-up of these survivors is important to monitor such late effects of treatment. It is also important to evaluate the risk of second primary neoplasms following more recent lower radiation dose treatment practices.

Research paper thumbnail of Hypothyroidism following childhood cancer therapy-an under diagnosed complication

International Journal of Cancer, 2012

To determine the prevalence of hypothyroidism amongst most adult survivors of childhood cancer in... more To determine the prevalence of hypothyroidism amongst most adult survivors of childhood cancer in Britain using the British Childhood Cancer Survivor Study (BCCSS). The BCCSS is a population based cohort of individuals diagnosed with childhood cancer between 1940 and 1991 and who survived at least 5 years from diagnosis (n 5 17,981). 10483, 71% of those survivors aged at least 16 years, returned a completed questionnaire, which asked if hypothyroidism had been diagnosed. Of the whole cohort, 7.7% reported hypothyroidism with the highest risk among patients treated for Hodgkin's disease (HD) (19.9%), CNS neoplasms (15.3%), Non-Hodgkin's lymphoma (6.2%) and leukaemia (5.2%). Survivors were more likely to develop hypothyroidism if they had received radiotherapy for HD (p 5 0.0001) or a CNS neoplasm (p < 0.00005) but not leukaemia (p 5 0.3). In these three patient groups, the frequency of hypothyroidism was similar in men and women. Survivors of irradiated CNS tumours reported a prevalence of hypothyroidism, which was substantially lower if discharged to primary care compared with being on hospital follow-up and which declined substantially with increased follow-up in both primary care (p 5 0.004) and hospital follow-up (p 5 0.023) settings. Hypothyroidism is a common finding amongst adult survivors of childhood malignancy. The substantial differences in reported hypothyroidism prevalence after irradiated CNS neoplasms suggests substantial under-diagnosis, which increased with increased follow-up, and which increased among those followed-up in primary care compared with hospital settings.

Research paper thumbnail of Long-term population-based risks of breast cancer after childhood cancer

International Journal of Cancer, 2008

Previous studies have reported substantially increased risks of breast cancer among survivors of ... more Previous studies have reported substantially increased risks of breast cancer among survivors of childhood cancer at 10-20 years posttreatment. Whether these excess risks are sustained beyond 40 years of age when general population incidence of breast cancer begins its steep increase is largely unknown. We quantified the risk of breast cancer in adult female survivors with considerably more survivors followed-up beyond 40 years of age than previously available. Standardized Incidence Ratios (SIR), Excess Absolute Risks (EAR), and cumulative incidence were calculated within a population-based cohort of 8,093 female survivors of childhood cancer. Poisson regression models were used to model SIRs and EARs in a multivariable setting. Eighty-one survivors developed a primary breast cancer, where 37.5 were expected (SIR5 2.2, 95% CI: 1.7-2.7). SIRs decreased significantly with increasing attained age (p trend < 0.001) to an SIR of 0.9 (95% CI: 0.5-1.8) at ages beyond 50 years; EARs increased significantly to about 40 years of age (p trend < 0.001) but then plateau. Between 30 and 49 years of age survivors experienced approximately 1 extra breast cancer per 1,000 survivors per year. Overall, 3% developed breast cancer by the age of 50. The substantially increased relative risks of breast cancer observed at 10-20 years postdiagnosis are not sustained into ages at which the risk of breast cancer in the general population becomes substantial. Among women who survived to an age of at least 50 years there is currently no evidence of an increased risk of breast cancer.

Research paper thumbnail of Diet in childhood and adult cardiovascular and all cause mortality: the Boyd Orr cohort

Heart, 2005

Objective: To examine the association between childhood diet and cardiovascular mortality. Design... more Objective: To examine the association between childhood diet and cardiovascular mortality. Design: Historical cohort study. Setting: 16 centres in England and Scotland. Participants: 4028 people (from 1234 families) who took part in Boyd Orr's survey of family diet and health in Britain between 1937 and 1939 followed up through the National Health Service central register.

Research paper thumbnail of Pregnancy Outcomes among Adult Survivors of Childhood Cancer in the British Childhood Cancer Survivor Study

Cancer Epidemiology Biomarkers & Prevention, 2009

We used data from the first large-scale overwhelmingly population-based study (a) to quantify the... more We used data from the first large-scale overwhelmingly population-based study (a) to quantify the risk of adverse pregnancy outcomes in survivors of childhood cancer in relation to cancer type and treatment and (b) to assess live birth rates relative to the general population. A questionnaire, including questions inquiring about pregnancy outcomes, was completed by 10,483 survivors. A total of 7,300 pregnancies were reported. Odds ratios (OR) for live birth, miscarriage, termination, stillbirth, premature birth, and low birth weight were calculated for different types of childhood cancer and by whether initial treatment involved chemotherapy and abdominal or brain irradiation. For females, the observed number of live births was compared with that expected based on the general population of England and Wales. Female survivors exposed to abdominal irradiation had a significantly increased OR of delivering preterm [OR, 3.2; 95% confidence interval (95% CI), 2.1-4.7] and producing offspring with a low birth weight (OR, 1.9; 95% CI, 1.1-3.2). An increased OR of miscarriage was also associated with abdominal radiotherapy (OR, 1.4; 95% CI, 1.0-1.9). The number of live births observed from all female survivors was two thirds of that expected (O/E, 0.64; 95% CI, 0.62-0.66) and lowest among survivors treated with brain (O/E, 0.52; 95% CI, 0.48-0.56) and abdominal radiotherapy (O/E, 0.55; 95% CI, 0.50-0.61). Female survivors of childhood cancer treated with abdominal radiotherapy are at 3-fold increased risk of delivering preterm, 2-fold increased risk of low birth weight, and a small increased risk of miscarriage. Overall, female survivors produce considerably fewer offspring than expected, particularly those treated with abdominal or brain radiotherapy.

Research paper thumbnail of Extent of Alcohol Consumption among Adult Survivors of Childhood Cancer: The British Childhood Cancer Survivor Study

Cancer Epidemiology Biomarkers & Prevention, 2010

Background: This study aimed to identify subgroups of childhood cancer survivors at highest risk ... more Background: This study aimed to identify subgroups of childhood cancer survivors at highest risk of consuming alcohol, consuming above recommended weekly levels, and consuming potentially harmful amounts and compare survivor risks with those expected from the general population.