E. Dicks - Academia.edu (original) (raw)

Papers by E. Dicks

Research paper thumbnail of Promoter methylation of Wnt5a is associated with microsatellite instability and BRAF V600E mutation in two large populations of colorectal cancer patients

British journal of cancer, Jan 7, 2011

In colorectal cancer (CRC), tumour microsatellite instability (MSI) status and CpG island methyla... more In colorectal cancer (CRC), tumour microsatellite instability (MSI) status and CpG island methylator phenotype (CIMP) status are indicators of patient outcome, but the molecular events that give rise to these outcomes remain largely unknown. Wnt5a is a critical regulator of non-canonical Wnt activity and promoter hypermethylation of this gene has emerging prognostic roles in CRC; however the frequency and prognostic significance of this epigenetic event have not been explored in the context of colorectal tumour subtype. Consequently, we investigated the frequency and prognostic significance of Wnt5a methylation in a large cohort of MSI-stratified CRCs. Methylation was quantified in a large cohort of 1232 colorectal carcinomas from two clinically distinct populations from Canada. Associations were examined between methylation status and clinicopathlogical features, including tumour MSI status, BRAF V600E mutation, and patient survival. In Ontario, Wnt5a methylation was strongly assoc...

Research paper thumbnail of MTHFR Glu429Ala and ERCC5 His46His Polymorphisms Are Associated with Prognosis in Colorectal Cancer Patients: Analysis of Two Independent Cohorts from Newfoundland

PLoS ONE, 2013

Introduction: In this study, 27 genetic polymorphisms that were previously reported to be associa... more Introduction: In this study, 27 genetic polymorphisms that were previously reported to be associated with clinical outcomes in colorectal cancer patients were investigated in relation to overall survival (OS) and disease free survival (DFS) in colorectal cancer patients from Newfoundland. Methods: The discovery and validation cohorts comprised of 532 and 252 patients, respectively. Genotypes of 27 polymorphisms were first obtained in the discovery cohort and survival analyses were performed assuming the codominant genetic model. Polymorphisms associated with disease outcomes in the discovery cohort were then investigated in the validation cohort. Results: When adjusted for sex, age, tumor stage and microsatellite instability (MSI) status, four polymorphisms were independent predictors of OS in the discovery cohort MTHFR Glu429Ala (HR: 1.72, 95%CI: 1.04-2.84, p = 0.036), ERCC5 His46His (HR: 1.78, 95%CI: 1.15-2.76, p = 0.01), SERPINE1 2675indelG (HR: 0.52, 95%CI: 0.32-0.84, p = 0.008), and the homozygous deletion of GSTM1 gene (HR: 1.4, 95%CI: 1.03-1.92, p = 0.033). In the validation cohort, the MTHFR Glu429Ala polymorphism was associated with shorter OS (HR: 1.71, 95%CI: 1.18-2.49, p = 0.005), although with a different genotype than the discovery cohort (CC genotype in the discovery cohort and AC genotype in the validation cohort). When stratified based on treatment with 5-Fluorouracil (5-FU)-based regimens, this polymorphism was associated with reduced OS only in patients not treated with 5-FU. In the DFS analysis, when adjusted for other variables, the TT genotype of the ERCC5 His46His polymorphism was associated with shorter DFS in both cohorts (discovery cohort: HR: 1.54, 95%CI: 1.04-2.29, p = 0.032 and replication cohort: HR: 1.81, 95%CI: 1.11-2.94, p = 0.018). Conclusions: In this study, associations of the MTHFR Glu429Ala polymorphism with OS and the ERCC5 His46His polymorphism with DFS were identified in two colorectal cancer patient cohorts. Our results also suggest that the MTHFR Glu429Ala polymorphism may be an adverse prognostic marker in patients not treated with 5-FU.

Research paper thumbnail of Genetics of Bardet-Biedl syndrome: obesity and the Newfoundland population

Progress in obesity …, 2003

... CHAPTER 69 Genetics of Bardet-Biedl syndrome: obesity and the Newfoundland population William... more ... CHAPTER 69 Genetics of Bardet-Biedl syndrome: obesity and the Newfoundland population William S. Davidson1, Yanli Fan1, Patrick S. Parfrey2, Elizabeth Dicks2, Susan Moore2 and Jane S. Green2 ^ Department ... Beales PL, Katsanis N, Lewis RA, Ansley SJ, Elcioglu N ef al. ...

Research paper thumbnail of Incident Renal Events and Risk Factors in Autosomal Dominant Polycystic Kidney Disease: A Population and Family-Based Cohort Followed for 22 Years

Clinical Journal of the American Society of Nephrology, 2006

Research paper thumbnail of Factors influencing surgical treatment decisions for breast cancer: a qualitative exploration of surgeon and patient perspectives

Current Oncology

Background The rate of mastectomy is much higher in Newfoundland and Labrador than in any other p... more Background The rate of mastectomy is much higher in Newfoundland and Labrador than in any other province in Canada, even for women diagnosed at an early stage. In this paper, we present qualitative data from women who have made a decision for surgical treatment and from breast surgeons in an effort to better explicate factors influencing breast cancer (bca) surgical decision-making.Methods The study’s descriptive, qualitative design involved holding interviews with breast surgeons and holding focus groups and interviews with women who were offered the choice of breast-conserving surgery (bcs) or mastectomy (mt).Results Participants included 35 women and 13 surgeons. High interest in mt and increasing requests for prophylactic contralateral mt were evident. A host of factors—clinical, demographic, psychosocial, education-related, and cultural—influenced the decisions. A key factor for women was fear of recurrence and a need to “just get rid of it,” but the experiences of others also ...

Research paper thumbnail of Reported intake of selected micronutrients and risk of colorectal cancer: results from a large population-based case-control study in Newfoundland, Labrador and Ontario, Canada

Anticancer research, 2012

The impact of micronutrient intake and colorectal cancer (CRC) risk is poorly understood. The obj... more The impact of micronutrient intake and colorectal cancer (CRC) risk is poorly understood. The objective of this study was to evaluate the associations of selected micronutrients with risk of incident CRC in study participants from Newfoundland, Labrador (NL) and Ontario (ON), Canada. We conducted a population-based study among 1760 case participants and 2481 age- and sex-matched control participants. Information on diet and other lifestyle factors were measured using a food frequency questionnaire and a personal history questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression, controlling for covariables. Highest compared to lowest quartile intakes of certain micronutrients were associated with lower risk of CRC, including: calcium (from food and supplements (FS), OR=0.59; 95% CI=0.45-0.77, and from food only (FO): OR=0.76, 95% CI=0.59-0.97), vitamin C (FS:OR=0.67; 95%CI:0.51-0.88), vitamin D (FS: OR=0.73; 95% CI: 0.57...

Research paper thumbnail of Attenuated Renal Disease Severity Associated with a Missense PKD1 Mutation

Research paper thumbnail of The natural history of Bardet-Biedl syndrome (BBS) by genotype: incident events in a longitudinal study

Research paper thumbnail of Multiple mutations in PKHD1 in a small Newfoundland community

Research paper thumbnail of Canadian Journal of Kidney Health and Disease: A Unique Launch of a Unique Journal

Canadian Journal of Kidney Health and Disease, 2014

Usually inaugural editorials are written by the Editor-in-Chief to describe the scope and vision ... more Usually inaugural editorials are written by the Editor-in-Chief to describe the scope and vision for the journal to potential authors and readers. This editorial is written by the Editor-in-Chief, the Deputy Editors and the Associate Editors collaboratively as a clear signal that this is a unique and different journal. We will build this journal on a set of principles which are fundamental to improving the outcomes of patients with kidney disease. To that end, we aim to be supportive, to collaborate, to integrate multiple perspectives and to be open to possibilities.

Research paper thumbnail of Hereditary colorectal cancer registries in Canada: report from the Colorectal Cancer Association of Canada consensus meeting; Montreal, Quebec; October 28, 2011

Current Oncology, 2013

md phd* |||| cancer organizations) responsible for prevention, service delivery, and funding deci... more md phd* |||| cancer organizations) responsible for prevention, service delivery, and funding decisions related to the management of patients and family members at high risk for crc. The recommendations provided here are based on presentations and discussions of the best available evidence. 2. BACKGROUND Since the establishment of the St. Mark's Hospital Polyposis Registry in London, England in 1924 1 , numerous successful high-risk crc and polyposis registries have been developed worldwide. In Canada, there are currently three well-established hcrcrs: the clinic-based Familial Gastrointestinal Cancer Registry 2 at Mount Sinai Hospital in Toronto, Ontario, supported by the Zane Cohen Centre for Digestive Diseases, and two research-based registries, the Ontario Familial Colorectal Cancer Registry 3 (part of the international Colon Cancer Family Registries funded by the National Institutes of Health in the United States) based in Toronto, Ontario, and the Newfoundland Colorectal Cancer Registry 4 at Memorial University in St. John's, Newfoundland and Labrador, which was funded by the Canadian Institutes of Health Research (grant numbers CRT-43821 and FRN-79845) and by the National Cancer Institute of Canada (grant numbers 18223 and 18226 until 2010). More recently, in 2011, The Ride to Conquer Cancer at the Jewish General Hospital has provided funding to help implement a hcrcr in Montreal, Quebec. Hereditary crc registries are typically multidisciplinary, offering genetic counselling and testing, colonic and extracolonic cancer screening, psychosocial services, patient and physician education, and research opportunities. Although the primary function may vary from centre to centre, the consensus group agreed on 11 roles that a hcrcr should play (Table ii), including identification of ABSTRACT At a consensus meeting held in Montreal, October 28, 2011, a multidisciplinary group of Canadian experts in the fields of genetics, gastroenterology, surgery, oncology, pathology, and health care services participated in presentation and discussion sessions for the purpose of developing consensus statements pertaining to the development and maintenance of hereditary colorectal cancer registries in Canada. Five statements were approved by all participants.

Research paper thumbnail of PREDICT Plus: development and validation of a prognostic model for early breast cancer that includes HER2

Research paper thumbnail of Association of total energy intake and macronutrient consumption with colorectal cancer risk: results from a large population-based case-control study in Newfoundland and Labrador and Ontario, Canada

Nutrition Journal, 2012

Background Diet is regarded as one of the most important environmental factors associated with co... more Background Diet is regarded as one of the most important environmental factors associated with colorectal cancer (CRC) risk. A recent report comprehensively concluded that total energy intake does not have a simple relationship with CRC risk, and that the data were inconsistent for carbohydrate, cholesterol and protein. The objective of this study was to identify the associations of CRC risk with dietary intakes of total energy, protein, fat, carbohydrate, fiber, and alcohol using data from a large case-control study conducted in Newfoundland and Labrador (NL) and Ontario (ON), Canada. Methods Incident colorectal cancer cases (n = 1760) were identified from population-based cancer registries in the provinces of ON (1997-2000) and NL (1999-2003). Controls (n = 2481) were a random sample of residents in each province, aged 20-74 years. Family history questionnaire (FHQ), personal history questionnaire (PHQ), and food frequency questionnaire (FFQ) were used to collect study data. Logis...

Research paper thumbnail of A missense mutation in PKD1 attenuates the severity of renal disease

Kidney International, 2012

Research paper thumbnail of Family History of Renal Disease Severity Predicts the Mutated Gene in ADPKD

Journal of the American Society of Nephrology, 2009

Research paper thumbnail of Public Attitudes About Genetic Testing in the Newborn Period

Journal of Obstetric, Gynecologic, & Neonatal Nursing, 2012

Objective: To measure attitudes toward newborn genetic testing in our jurisdiction. Design: A cro... more Objective: To measure attitudes toward newborn genetic testing in our jurisdiction. Design: A cross-sectional, pen-and-paper survey. Setting: The survey was administered to the general public and prospective parents in Eastern Canada between April 2010 and December 2010. Participants: A total of 648 individuals completed surveys. Results: Positive attitudes were found toward newborn genetic testing, regardless of whether an effective treatment existed for the disorder in question or whether the disorder developed in adulthood. A majority agreed (69%) that testing should be available for any condition to assist with future reproductive decisions. Most respondents (93%) agreed parents should provide informed consent before newborn screening (NBS) was undertaken and that parents had a fundamental right to access NBS if they so choose. Conclusion: Interest in NBS for genetic disorders is generally high, regardless of whether an effective treatment exists. Findings lend support to the expansion of NBS panels to include those disorders currently lacking treatment but highlight consumers' desire for informed consent before testing is undertaken.

Research paper thumbnail of MLH1 -93G>A Promoter Polymorphism and the Risk of Microsatellite-Unstable Colorectal Cancer

JNCI Journal of the National Cancer Institute, 2007

Research paper thumbnail of The genetic basis of colorectal cancer in a population-based incident cohort with a high rate of familial disease

Research paper thumbnail of Impact of gynecological screening in Lynch syndrome carriers with an MSH2 mutation

Clinical Genetics, 2013

Lifetime risk of developing endometrial cancer in Lynch syndrome carriers is very high and female... more Lifetime risk of developing endometrial cancer in Lynch syndrome carriers is very high and females are also at an increased risk of developing ovarian cancer. The aim of the study was to determine the impact of gynecological screening in MSH2 mutation carriers. Gynecological cancer incidence and overall survival was compared in female mutation carriers who received gynecological screening (cases) and in matched controls. Controls were randomly selected from non-screened mutation carriers who were alive and disease-free at the age the case entered the screening program. Median age to diagnosis of gynecological cancer was 54 years in the screened group compared to 56 years in controls (p = 0.50). Stage I or II cancer was diagnosed in 92% of screened patients compared to 71% in the control group (p = 0.17). Two of three deaths in the screened group were the result of ovarian cancer. Mean survival in the screened group was 79 years compared to 69 years in the control group (p = 0.11), likely associated with concomitant colonoscopy screening. Gynecological screening did not result in earlier gynecologic cancer detection and despite screening two young women died from ovarian cancer suggesting that prophylactic hysterectomy with bilateral salpingo-oophorectomy be considered in female mutation carriers who have completed childbearing.

Research paper thumbnail of A population-based study of hereditary non-polyposis colorectal cancer: evidence of pathologic and genetic heterogeneity

Clinical Genetics, 2013

Hereditary non-polyposis colorectal cancer (HNPCC) may be the result of Lynch syndrome (LS) cause... more Hereditary non-polyposis colorectal cancer (HNPCC) may be the result of Lynch syndrome (LS) caused by mutations in mismatch repair (MMR) genes, a syndrome of unknown etiology called familial colorectal cancer type-X (FCCTX), or familial serrated neoplasia associated with the colorectal cancer (CRC) somatic BRAF mutation. To determine the cause of HNPCC in the founder population of the island of Newfoundland, we studied 37 families with LS and 29 families without LS who fulfilled the Amsterdam I criteria. In non-LS, four index CRCs were BRAF mutation positive, one of which was microsatellite instable. Geographic clustering of LS families caused by three different founder mutations in MSH2 was observed. Nine unique MMR mutations in four MMR genes were identified in single families distributed in different geographic isolates. The geographic distribution of non-LS was similar to LS. The coefficient of relatedness using genotype data was significantly higher for non-LS than for all CRC. Extensive genealogic investigation failed to connect non-LS families and in some clusters pathologic CRC heterogeneity was observed. We conclude that non-LS HNPCC may be a heterogeneous disorder with different pathogenic pathways, and that the geographic distribution is consistent with multiple different mutations in unknown CRC susceptibility gene(s).

Research paper thumbnail of Promoter methylation of Wnt5a is associated with microsatellite instability and BRAF V600E mutation in two large populations of colorectal cancer patients

British journal of cancer, Jan 7, 2011

In colorectal cancer (CRC), tumour microsatellite instability (MSI) status and CpG island methyla... more In colorectal cancer (CRC), tumour microsatellite instability (MSI) status and CpG island methylator phenotype (CIMP) status are indicators of patient outcome, but the molecular events that give rise to these outcomes remain largely unknown. Wnt5a is a critical regulator of non-canonical Wnt activity and promoter hypermethylation of this gene has emerging prognostic roles in CRC; however the frequency and prognostic significance of this epigenetic event have not been explored in the context of colorectal tumour subtype. Consequently, we investigated the frequency and prognostic significance of Wnt5a methylation in a large cohort of MSI-stratified CRCs. Methylation was quantified in a large cohort of 1232 colorectal carcinomas from two clinically distinct populations from Canada. Associations were examined between methylation status and clinicopathlogical features, including tumour MSI status, BRAF V600E mutation, and patient survival. In Ontario, Wnt5a methylation was strongly assoc...

Research paper thumbnail of MTHFR Glu429Ala and ERCC5 His46His Polymorphisms Are Associated with Prognosis in Colorectal Cancer Patients: Analysis of Two Independent Cohorts from Newfoundland

PLoS ONE, 2013

Introduction: In this study, 27 genetic polymorphisms that were previously reported to be associa... more Introduction: In this study, 27 genetic polymorphisms that were previously reported to be associated with clinical outcomes in colorectal cancer patients were investigated in relation to overall survival (OS) and disease free survival (DFS) in colorectal cancer patients from Newfoundland. Methods: The discovery and validation cohorts comprised of 532 and 252 patients, respectively. Genotypes of 27 polymorphisms were first obtained in the discovery cohort and survival analyses were performed assuming the codominant genetic model. Polymorphisms associated with disease outcomes in the discovery cohort were then investigated in the validation cohort. Results: When adjusted for sex, age, tumor stage and microsatellite instability (MSI) status, four polymorphisms were independent predictors of OS in the discovery cohort MTHFR Glu429Ala (HR: 1.72, 95%CI: 1.04-2.84, p = 0.036), ERCC5 His46His (HR: 1.78, 95%CI: 1.15-2.76, p = 0.01), SERPINE1 2675indelG (HR: 0.52, 95%CI: 0.32-0.84, p = 0.008), and the homozygous deletion of GSTM1 gene (HR: 1.4, 95%CI: 1.03-1.92, p = 0.033). In the validation cohort, the MTHFR Glu429Ala polymorphism was associated with shorter OS (HR: 1.71, 95%CI: 1.18-2.49, p = 0.005), although with a different genotype than the discovery cohort (CC genotype in the discovery cohort and AC genotype in the validation cohort). When stratified based on treatment with 5-Fluorouracil (5-FU)-based regimens, this polymorphism was associated with reduced OS only in patients not treated with 5-FU. In the DFS analysis, when adjusted for other variables, the TT genotype of the ERCC5 His46His polymorphism was associated with shorter DFS in both cohorts (discovery cohort: HR: 1.54, 95%CI: 1.04-2.29, p = 0.032 and replication cohort: HR: 1.81, 95%CI: 1.11-2.94, p = 0.018). Conclusions: In this study, associations of the MTHFR Glu429Ala polymorphism with OS and the ERCC5 His46His polymorphism with DFS were identified in two colorectal cancer patient cohorts. Our results also suggest that the MTHFR Glu429Ala polymorphism may be an adverse prognostic marker in patients not treated with 5-FU.

Research paper thumbnail of Genetics of Bardet-Biedl syndrome: obesity and the Newfoundland population

Progress in obesity …, 2003

... CHAPTER 69 Genetics of Bardet-Biedl syndrome: obesity and the Newfoundland population William... more ... CHAPTER 69 Genetics of Bardet-Biedl syndrome: obesity and the Newfoundland population William S. Davidson1, Yanli Fan1, Patrick S. Parfrey2, Elizabeth Dicks2, Susan Moore2 and Jane S. Green2 ^ Department ... Beales PL, Katsanis N, Lewis RA, Ansley SJ, Elcioglu N ef al. ...

Research paper thumbnail of Incident Renal Events and Risk Factors in Autosomal Dominant Polycystic Kidney Disease: A Population and Family-Based Cohort Followed for 22 Years

Clinical Journal of the American Society of Nephrology, 2006

Research paper thumbnail of Factors influencing surgical treatment decisions for breast cancer: a qualitative exploration of surgeon and patient perspectives

Current Oncology

Background The rate of mastectomy is much higher in Newfoundland and Labrador than in any other p... more Background The rate of mastectomy is much higher in Newfoundland and Labrador than in any other province in Canada, even for women diagnosed at an early stage. In this paper, we present qualitative data from women who have made a decision for surgical treatment and from breast surgeons in an effort to better explicate factors influencing breast cancer (bca) surgical decision-making.Methods The study’s descriptive, qualitative design involved holding interviews with breast surgeons and holding focus groups and interviews with women who were offered the choice of breast-conserving surgery (bcs) or mastectomy (mt).Results Participants included 35 women and 13 surgeons. High interest in mt and increasing requests for prophylactic contralateral mt were evident. A host of factors—clinical, demographic, psychosocial, education-related, and cultural—influenced the decisions. A key factor for women was fear of recurrence and a need to “just get rid of it,” but the experiences of others also ...

Research paper thumbnail of Reported intake of selected micronutrients and risk of colorectal cancer: results from a large population-based case-control study in Newfoundland, Labrador and Ontario, Canada

Anticancer research, 2012

The impact of micronutrient intake and colorectal cancer (CRC) risk is poorly understood. The obj... more The impact of micronutrient intake and colorectal cancer (CRC) risk is poorly understood. The objective of this study was to evaluate the associations of selected micronutrients with risk of incident CRC in study participants from Newfoundland, Labrador (NL) and Ontario (ON), Canada. We conducted a population-based study among 1760 case participants and 2481 age- and sex-matched control participants. Information on diet and other lifestyle factors were measured using a food frequency questionnaire and a personal history questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression, controlling for covariables. Highest compared to lowest quartile intakes of certain micronutrients were associated with lower risk of CRC, including: calcium (from food and supplements (FS), OR=0.59; 95% CI=0.45-0.77, and from food only (FO): OR=0.76, 95% CI=0.59-0.97), vitamin C (FS:OR=0.67; 95%CI:0.51-0.88), vitamin D (FS: OR=0.73; 95% CI: 0.57...

Research paper thumbnail of Attenuated Renal Disease Severity Associated with a Missense PKD1 Mutation

Research paper thumbnail of The natural history of Bardet-Biedl syndrome (BBS) by genotype: incident events in a longitudinal study

Research paper thumbnail of Multiple mutations in PKHD1 in a small Newfoundland community

Research paper thumbnail of Canadian Journal of Kidney Health and Disease: A Unique Launch of a Unique Journal

Canadian Journal of Kidney Health and Disease, 2014

Usually inaugural editorials are written by the Editor-in-Chief to describe the scope and vision ... more Usually inaugural editorials are written by the Editor-in-Chief to describe the scope and vision for the journal to potential authors and readers. This editorial is written by the Editor-in-Chief, the Deputy Editors and the Associate Editors collaboratively as a clear signal that this is a unique and different journal. We will build this journal on a set of principles which are fundamental to improving the outcomes of patients with kidney disease. To that end, we aim to be supportive, to collaborate, to integrate multiple perspectives and to be open to possibilities.

Research paper thumbnail of Hereditary colorectal cancer registries in Canada: report from the Colorectal Cancer Association of Canada consensus meeting; Montreal, Quebec; October 28, 2011

Current Oncology, 2013

md phd* |||| cancer organizations) responsible for prevention, service delivery, and funding deci... more md phd* |||| cancer organizations) responsible for prevention, service delivery, and funding decisions related to the management of patients and family members at high risk for crc. The recommendations provided here are based on presentations and discussions of the best available evidence. 2. BACKGROUND Since the establishment of the St. Mark's Hospital Polyposis Registry in London, England in 1924 1 , numerous successful high-risk crc and polyposis registries have been developed worldwide. In Canada, there are currently three well-established hcrcrs: the clinic-based Familial Gastrointestinal Cancer Registry 2 at Mount Sinai Hospital in Toronto, Ontario, supported by the Zane Cohen Centre for Digestive Diseases, and two research-based registries, the Ontario Familial Colorectal Cancer Registry 3 (part of the international Colon Cancer Family Registries funded by the National Institutes of Health in the United States) based in Toronto, Ontario, and the Newfoundland Colorectal Cancer Registry 4 at Memorial University in St. John's, Newfoundland and Labrador, which was funded by the Canadian Institutes of Health Research (grant numbers CRT-43821 and FRN-79845) and by the National Cancer Institute of Canada (grant numbers 18223 and 18226 until 2010). More recently, in 2011, The Ride to Conquer Cancer at the Jewish General Hospital has provided funding to help implement a hcrcr in Montreal, Quebec. Hereditary crc registries are typically multidisciplinary, offering genetic counselling and testing, colonic and extracolonic cancer screening, psychosocial services, patient and physician education, and research opportunities. Although the primary function may vary from centre to centre, the consensus group agreed on 11 roles that a hcrcr should play (Table ii), including identification of ABSTRACT At a consensus meeting held in Montreal, October 28, 2011, a multidisciplinary group of Canadian experts in the fields of genetics, gastroenterology, surgery, oncology, pathology, and health care services participated in presentation and discussion sessions for the purpose of developing consensus statements pertaining to the development and maintenance of hereditary colorectal cancer registries in Canada. Five statements were approved by all participants.

Research paper thumbnail of PREDICT Plus: development and validation of a prognostic model for early breast cancer that includes HER2

Research paper thumbnail of Association of total energy intake and macronutrient consumption with colorectal cancer risk: results from a large population-based case-control study in Newfoundland and Labrador and Ontario, Canada

Nutrition Journal, 2012

Background Diet is regarded as one of the most important environmental factors associated with co... more Background Diet is regarded as one of the most important environmental factors associated with colorectal cancer (CRC) risk. A recent report comprehensively concluded that total energy intake does not have a simple relationship with CRC risk, and that the data were inconsistent for carbohydrate, cholesterol and protein. The objective of this study was to identify the associations of CRC risk with dietary intakes of total energy, protein, fat, carbohydrate, fiber, and alcohol using data from a large case-control study conducted in Newfoundland and Labrador (NL) and Ontario (ON), Canada. Methods Incident colorectal cancer cases (n = 1760) were identified from population-based cancer registries in the provinces of ON (1997-2000) and NL (1999-2003). Controls (n = 2481) were a random sample of residents in each province, aged 20-74 years. Family history questionnaire (FHQ), personal history questionnaire (PHQ), and food frequency questionnaire (FFQ) were used to collect study data. Logis...

Research paper thumbnail of A missense mutation in PKD1 attenuates the severity of renal disease

Kidney International, 2012

Research paper thumbnail of Family History of Renal Disease Severity Predicts the Mutated Gene in ADPKD

Journal of the American Society of Nephrology, 2009

Research paper thumbnail of Public Attitudes About Genetic Testing in the Newborn Period

Journal of Obstetric, Gynecologic, & Neonatal Nursing, 2012

Objective: To measure attitudes toward newborn genetic testing in our jurisdiction. Design: A cro... more Objective: To measure attitudes toward newborn genetic testing in our jurisdiction. Design: A cross-sectional, pen-and-paper survey. Setting: The survey was administered to the general public and prospective parents in Eastern Canada between April 2010 and December 2010. Participants: A total of 648 individuals completed surveys. Results: Positive attitudes were found toward newborn genetic testing, regardless of whether an effective treatment existed for the disorder in question or whether the disorder developed in adulthood. A majority agreed (69%) that testing should be available for any condition to assist with future reproductive decisions. Most respondents (93%) agreed parents should provide informed consent before newborn screening (NBS) was undertaken and that parents had a fundamental right to access NBS if they so choose. Conclusion: Interest in NBS for genetic disorders is generally high, regardless of whether an effective treatment exists. Findings lend support to the expansion of NBS panels to include those disorders currently lacking treatment but highlight consumers' desire for informed consent before testing is undertaken.

Research paper thumbnail of MLH1 -93G>A Promoter Polymorphism and the Risk of Microsatellite-Unstable Colorectal Cancer

JNCI Journal of the National Cancer Institute, 2007

Research paper thumbnail of The genetic basis of colorectal cancer in a population-based incident cohort with a high rate of familial disease

Research paper thumbnail of Impact of gynecological screening in Lynch syndrome carriers with an MSH2 mutation

Clinical Genetics, 2013

Lifetime risk of developing endometrial cancer in Lynch syndrome carriers is very high and female... more Lifetime risk of developing endometrial cancer in Lynch syndrome carriers is very high and females are also at an increased risk of developing ovarian cancer. The aim of the study was to determine the impact of gynecological screening in MSH2 mutation carriers. Gynecological cancer incidence and overall survival was compared in female mutation carriers who received gynecological screening (cases) and in matched controls. Controls were randomly selected from non-screened mutation carriers who were alive and disease-free at the age the case entered the screening program. Median age to diagnosis of gynecological cancer was 54 years in the screened group compared to 56 years in controls (p = 0.50). Stage I or II cancer was diagnosed in 92% of screened patients compared to 71% in the control group (p = 0.17). Two of three deaths in the screened group were the result of ovarian cancer. Mean survival in the screened group was 79 years compared to 69 years in the control group (p = 0.11), likely associated with concomitant colonoscopy screening. Gynecological screening did not result in earlier gynecologic cancer detection and despite screening two young women died from ovarian cancer suggesting that prophylactic hysterectomy with bilateral salpingo-oophorectomy be considered in female mutation carriers who have completed childbearing.

Research paper thumbnail of A population-based study of hereditary non-polyposis colorectal cancer: evidence of pathologic and genetic heterogeneity

Clinical Genetics, 2013

Hereditary non-polyposis colorectal cancer (HNPCC) may be the result of Lynch syndrome (LS) cause... more Hereditary non-polyposis colorectal cancer (HNPCC) may be the result of Lynch syndrome (LS) caused by mutations in mismatch repair (MMR) genes, a syndrome of unknown etiology called familial colorectal cancer type-X (FCCTX), or familial serrated neoplasia associated with the colorectal cancer (CRC) somatic BRAF mutation. To determine the cause of HNPCC in the founder population of the island of Newfoundland, we studied 37 families with LS and 29 families without LS who fulfilled the Amsterdam I criteria. In non-LS, four index CRCs were BRAF mutation positive, one of which was microsatellite instable. Geographic clustering of LS families caused by three different founder mutations in MSH2 was observed. Nine unique MMR mutations in four MMR genes were identified in single families distributed in different geographic isolates. The geographic distribution of non-LS was similar to LS. The coefficient of relatedness using genotype data was significantly higher for non-LS than for all CRC. Extensive genealogic investigation failed to connect non-LS families and in some clusters pathologic CRC heterogeneity was observed. We conclude that non-LS HNPCC may be a heterogeneous disorder with different pathogenic pathways, and that the geographic distribution is consistent with multiple different mutations in unknown CRC susceptibility gene(s).