COHORT STUDY OF GENETIC SUSCEPTIBILITY TO BREAST CANCER

Summary

Principal Investigator: DAVID JOHN HUNTER
Abstract: DESCRIPTION (provided by applicant): We propose to continue our study of the environmental and inherited determinants of breast cancer in women. Telomere length, measured in peripheral blood white cells, has emerged as a biomarker of ageing, and cancer risk. Telomeres are TTAGGG repeat complexes at the end of chromosomes, that protect against degradation, fusion, and aberrant recombination of chromosomes. As telomeres shorten with each cell replication cycle, they are an indicator of the number of cell divisions a cell has undergone. Shorter telomere length has been associated with risks of head and neck, lung, renal cell and bladder cancers, however, no studies of breast cancer have been published, although telomere length has been shown to shorten in normal breast tissue in older women. Twin studies have shown that telomere length has a substantial heritable component, however, no genetic variants have been linked to telomere length. We propose to (i) Establish whether telomere length in peripheral white blood cells is a predictor of breast cancer risk in premenopausal and postmenopausal breast cancer from the Nurses'Health Studies I and II, and postmenopausal women from the Women's Health Study;(ii) use a multistage design starting with a completed whole genome SNP scan among 2400 postmenopausal women in NHS I to locate the inherited genetic variants associated with rate of telomere shortening;and (iii) examine the environmental and lifestyle predictors of telomere length. Among the novel aspects of this project is that it will be one of the first to apply dense data from a whole genome SNP scan to a continuous quantitative outcome. This project will integrate the genetic and environmental determinants of telomere length for the first time, and should give insight into the biological and modifiable causes of age-related cancers. Telomeres are repeated nucleotide sequences that protect the ends of our chromosomes from degradation. They get shortened during a cell's life and thus represent a marker of aging. We will examine whether shorter telomeres in white blood cells are a marker of a woman's risk of breast cancer, and seek the genetic and lifestyle determinants of shorter telomeres. Understanding the causes of the age-related shortening of telomeres may offer modifiable means of reducing breast cancer risk.
Funding Period: ----------------1996 - ---------------2011-
more information: NIH RePORT

Top Publications

  1. pmc Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits
    Joshua C Randall
    Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom
    PLoS Genet 9:e1003500. 2013
  2. pmc Disparities in child abuse victimization in lesbian, bisexual, and heterosexual women in the Nurses' Health Study II
    S Bryn Austin
    Division of Adolescent and Young Adult Medicine, Children s Hospital, Boston, Massachusetts 02115, USA
    J Womens Health (Larchmt) 17:597-606. 2008
  3. pmc Population substructure and control selection in genome-wide association studies
    Kai Yu
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, United States of America
    PLoS ONE 3:e2551. 2008
  4. pmc Common variants of FUT2 are associated with plasma vitamin B12 levels
    Aditi Hazra
    Department of Epidemiology, Harvard School of Public Health, Program in Molecular and Genetic Epidemiology, Boston, Massachusetts 02115, USA
    Nat Genet 40:1160-2. 2008
  5. pmc The mediating effect of childhood abuse in sexual orientation disparities in tobacco and alcohol use during adolescence: results from the Nurses' Health Study II
    Hee Jin Jun
    Channing Laboratory, Brigham and Women s Hospital and Harvard Medical School, Boston, MA, USA
    Cancer Causes Control 21:1817-28. 2010
  6. pmc Genetic modifiers of menopausal hormone replacement therapy and breast cancer risk: a genome-wide interaction study
    Anja Rudolph
    Division of Cancer Epidemiology, German Cancer Research Center DKFZ, Im Neuenheimer Feld 581, D 69120 Heidelberg, Germany PMV Research Group at the Department of Child and Adolescent Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA Foundation for Quality and Efficiency in Health Care IQWIG, Cologne, Germany Human Genetics, Genome Institute of Singapore, Singapore, Singapore Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK INSERM National Institute of Health and Medical Research, CESP Center for Research in Epidemiology and Population Health, U1018, Environmental Epidemiology of Cancer, Villejuif, France Unité Mixte de Recherche Scientifique UMRS 1018, University Paris Sud, Villejuif, France Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr Universität Bochum IPA, Bochum, Germany Institute for Occupational Medicine and Maritime Medicine, University Medical Center, Hamburg Eppendorf, Hamburg, Germany Department of Internal Medicine, Telos Pharmaceuticals LLC
    Endocr Relat Cancer 20:875-87. 2013
  7. pmc An examination of sexual orientation group patterns in mammographic and colorectal screening in a cohort of U.S. women
    S Bryn Austin
    Channing Laboratory, Brigham and Women s Hospital and Harvard Medical School, Boston, MA, USA
    Cancer Causes Control 24:539-47. 2013
  8. pmc High phobic anxiety is related to lower leukocyte telomere length in women
    Olivia I Okereke
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS ONE 7:e40516. 2012
  9. pmc Paternal age at birth is associated with offspring leukocyte telomere length in the nurses' health study
    J Prescott
    Channing Division of Network Medicine, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, 181 Longwood Ave, Boston, MA 02115, USA
    Hum Reprod 27:3622-31. 2012
  10. pmc A meta-analysis of genome-wide association studies of breast cancer identifies two novel susceptibility loci at 6q14 and 20q11
    Afshan Siddiq
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
    Hum Mol Genet 21:5373-84. 2012

Scientific Experts

  • Immaculata DeVivo
  • J E Chavarro
  • Aditi Hazra
  • David G Cox
  • Alison M Dunning
  • Chunyan He
  • Jingmei Li
  • David J Hunter
  • Peter Kraft
  • Stephen J Chanock
  • Susan E Hankinson
  • S Bryn Austin
  • Per Hall
  • Kevin B Jacobs
  • Jennifer Prescott
  • Jianjun Liu
  • Albert Hofman
  • Rebecca Hein
  • Andre G Uitterlinden
  • Thomas Illig
  • Immaculata De Vivo
  • Daniel I Chasman
  • Cornelia M van Duijn
  • Joshua C Randall
  • Fernando Rivadeneira
  • Sonja I Berndt
  • Elizabeth K Speliotes
  • Iris M Heid
  • Donna Spiegelman
  • Zhaoming Wang
  • Robert N Hoover
  • Richard B Hayes
  • Gilles Thomas
  • Hiltrud Brauch
  • Jenny Chang-Claude
  • Douglas F Easton
  • Kamila Czene
  • Najaf Amin
  • Jolanta Lissowska
  • Johan G Eriksson
  • Montserrat Garcia-Closas
  • Paul M Ridker
  • Lu Qi
  • Leif C Groop
  • Hee Jin Jun
  • Inga Prokopenko
  • Michael Boehnke
  • Nicholas J Wareham
  • Wendy L McArdle
  • Patricia B Munroe
  • Jing Hua Zhao
  • Anne U Jackson
  • Ines Barroso
  • Marjo Riitta Jarvelin
  • Mark J Caulfield
  • M Carola Zillikens
  • Ruth J F Loos
  • H Erich Wichmann
  • Jaakko Tuomilehto
  • Veikko Salomaa
  • Mark I McCarthy
  • Joel N Hirschhorn
  • Frank B Hu
  • Massimo Mangino
  • Goncalo R Abecasis
  • David P Strachan
  • Cecilia M Lindgren
  • Toby Johnson
  • Karol Estrada
  • Karen L Mohlke
  • Francis S Collins
  • David Schlessinger
  • Jian An Luan
  • Nilesh J Samani
  • Kristian Hveem
  • Saundra S Buys
  • Michael J Thun
  • Regina G Ziegler
  • Christine D Berg
  • Heather Spencer Feigelson
  • Cristen J Willer
  • Nilanjan Chatterjee
  • Jiali Han
  • Fergus J Couch
  • Sara Lindstrom
  • Dieter Flesch-Janys
  • Xianshu Wang
  • Julian Peto
  • Mathew J Pazaris
  • Gianluca Severi

Detail Information

Publications51

  1. pmc Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits
    Joshua C Randall
    Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom
    PLoS Genet 9:e1003500. 2013
    ..The PPARG locus is of specific interest due to its role in diabetes genetics and therapy. Our results demonstrate the value of sex-specific GWAS to unravel the sexually dimorphic genetic underpinning of complex traits...
  2. pmc Disparities in child abuse victimization in lesbian, bisexual, and heterosexual women in the Nurses' Health Study II
    S Bryn Austin
    Division of Adolescent and Young Adult Medicine, Children s Hospital, Boston, Massachusetts 02115, USA
    J Womens Health (Larchmt) 17:597-606. 2008
    ..One underlying factor may be heightened risk for abuse victimization in childhood in lesbian and bisexual women...
  3. pmc Population substructure and control selection in genome-wide association studies
    Kai Yu
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, United States of America
    PLoS ONE 3:e2551. 2008
    ..A study using suboptimal controls can have acceptable type I error when an effective strategy for the correction of PS is employed...
  4. pmc Common variants of FUT2 are associated with plasma vitamin B12 levels
    Aditi Hazra
    Department of Epidemiology, Harvard School of Public Health, Program in Molecular and Genetic Epidemiology, Boston, Massachusetts 02115, USA
    Nat Genet 40:1160-2. 2008
    ..This allele is in strong linkage disequilibrium with the FUT2 nonsecretor variant encoding W143X, suggesting a plausible mechanism for altered B(12) absorption and plasma levels...
  5. pmc The mediating effect of childhood abuse in sexual orientation disparities in tobacco and alcohol use during adolescence: results from the Nurses' Health Study II
    Hee Jin Jun
    Channing Laboratory, Brigham and Women s Hospital and Harvard Medical School, Boston, MA, USA
    Cancer Causes Control 21:1817-28. 2010
    ..To examine the mediating effect of childhood abuse on sexual orientation disparities in tobacco and alcohol use during adolescence...
  6. pmc Genetic modifiers of menopausal hormone replacement therapy and breast cancer risk: a genome-wide interaction study
    Anja Rudolph
    Division of Cancer Epidemiology, German Cancer Research Center DKFZ, Im Neuenheimer Feld 581, D 69120 Heidelberg, Germany PMV Research Group at the Department of Child and Adolescent Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA Foundation for Quality and Efficiency in Health Care IQWIG, Cologne, Germany Human Genetics, Genome Institute of Singapore, Singapore, Singapore Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK INSERM National Institute of Health and Medical Research, CESP Center for Research in Epidemiology and Population Health, U1018, Environmental Epidemiology of Cancer, Villejuif, France Unité Mixte de Recherche Scientifique UMRS 1018, University Paris Sud, Villejuif, France Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr Universität Bochum IPA, Bochum, Germany Institute for Occupational Medicine and Maritime Medicine, University Medical Center, Hamburg Eppendorf, Hamburg, Germany Department of Internal Medicine, Telos Pharmaceuticals LLC
    Endocr Relat Cancer 20:875-87. 2013
    ..These findings warrant replication in independent studies...
  7. pmc An examination of sexual orientation group patterns in mammographic and colorectal screening in a cohort of U.S. women
    S Bryn Austin
    Channing Laboratory, Brigham and Women s Hospital and Harvard Medical School, Boston, MA, USA
    Cancer Causes Control 24:539-47. 2013
    ..Underutilization of cancer screening has been found especially to affect socially marginalized groups. We investigated sexual orientation group patterns in breast and colorectal cancer screening adherence...
  8. pmc High phobic anxiety is related to lower leukocyte telomere length in women
    Olivia I Okereke
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS ONE 7:e40516. 2012
    ..Yet, little is known about relations of anxiety to telomeres. We examined whether a typically chronic form of anxiety--phobic anxiety--is related to telomere length...
  9. pmc Paternal age at birth is associated with offspring leukocyte telomere length in the nurses' health study
    J Prescott
    Channing Division of Network Medicine, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, 181 Longwood Ave, Boston, MA 02115, USA
    Hum Reprod 27:3622-31. 2012
    ..Is the association between paternal age at birth and offspring leukocyte telomere length (LTL) an artifact of early life socioeconomic status (SES)?..
  10. pmc A meta-analysis of genome-wide association studies of breast cancer identifies two novel susceptibility loci at 6q14 and 20q11
    Afshan Siddiq
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
    Hum Mol Genet 21:5373-84. 2012
    ..Our results highlight the value of large-scale collaborative studies to identify novel breast cancer risk loci...
  11. pmc Application of the Rosner-Colditz risk prediction model to estimate sexual orientation group disparities in breast cancer risk in a U.S. cohort of premenopausal women
    S Bryn Austin
    Division of Adolescent and Young Adult Medicine, Children s Hospital, 300 Longwood Ave, Boston, MA 02115, USA
    Cancer Epidemiol Biomarkers Prev 21:2201-8. 2012
    ..Lesbian and bisexual women may be at greater risk of breast cancer than heterosexual women during the premenopausal period due to disparities in risk factors...
  12. pmc A genome-wide association study of depressive symptoms
    Karin Hek
    Research Centre O3, Department of Psychiatry, Erasmus MC, Rotterdam, The Netherlands Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands
    Biol Psychiatry 73:667-78. 2013
    ..Yet, the search for genetic variants associated with depression has had few successes. We exploit the entire continuum of depression to find common variants for depressive symptoms...
  13. pmc A genome-wide association study to identify genetic susceptibility loci that modify ductal and lobular postmenopausal breast cancer risk associated with menopausal hormone therapy use: a two-stage design with replication
    Rebecca Hein
    Unit of Genetic Epidemiology, Division of Cancer Epidemiology C020, German Cancer Research Center DKFZ, Im Neuenheimer Feld 581, 69120, Heidelberg, Germany
    Breast Cancer Res Treat 138:529-42. 2013
    ..Our study, however, suggests that there are unlikely to be SNPs that interact strongly enough with MHT use to be clinically significant in European women...
  14. pmc Genetic predisposition to higher body mass index or type 2 diabetes and leukocyte telomere length in the Nurses' Health Study
    Mengmeng Du
    Department of Epidemiology, University of Washington School of Public Health, Seattle, Washington, United States of America
    PLoS ONE 8:e52240. 2013
    ..We therefore examined whether genetic predisposition to higher BMI or T2D was associated with shortened leukocyte telomere length (LTL)...
  15. pmc A nonparametric test to detect quantitative trait loci where the phenotypic distribution differs by genotypes
    Hugues Aschard
    Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA
    Genet Epidemiol 37:323-33. 2013
    ..We demonstrate the potential utility of our method on real data by analyzing mammographic density genome-wide data from the Nurses' Health Study...
  16. pmc Large-scale genotyping identifies 41 new loci associated with breast cancer risk
    Kyriaki Michailidou
    Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
    Nat Genet 45:353-61, 361e1-2. 2013
    ..We identified SNPs at 41 new breast cancer susceptibility loci at genome-wide significance (P < 5 × 10(-8)). Further analyses suggest that more than 1,000 additional loci are involved in breast cancer susceptibility...
  17. pmc Postmenopausal hormone therapy and stroke: role of time since menopause and age at initiation of hormone therapy
    Francine Grodstein
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, 181 Longwood Ave, Boston, Massachusetts 02115, USA
    Arch Intern Med 168:861-6. 2008
    ..We evaluated stroke risk associated with hormone therapy (HT) in younger women, in recently menopausal women, and in older women...
  18. pmc Gene x Gene interaction between MnSOD and GPX-1 and breast cancer risk: a nested case-control study
    David G Cox
    Program in Molecular and Genetic Epidemiology, Epidemiology Department, Harvard School of Public Health, 677 Huntington Ave, Boston, MA 02115, USA
    BMC Cancer 6:217. 2006
    ..We investigated whether variants at both polymorphisms, while not independently associated with breast cancer risk, could influence breast cancer risk when considered together...
  19. pmc A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer
    David J Hunter
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Genet 39:870-4. 2007
    ..Our summary results from the GWAS are available online in a form that should speed the identification of additional risk loci...
  20. ncbi The p53 Arg72Pro and MDM2 -309 polymorphisms and risk of breast cancer in the nurses' health studies
    David G Cox
    Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA
    Cancer Causes Control 18:621-5. 2007
    ..Neither SNP is independently associated with overall breast cancer risk. Some indication of gene-by-gene interaction was observed; however, no consistent direction of interaction was apparent...
  21. ncbi A prospective study of dairy foods intake and anovulatory infertility
    J E Chavarro
    Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115, USA
    Hum Reprod 22:1340-7. 2007
    ..Yet, few studies have been conducted in humans and their results are inconsistent. We evaluated whether intake of dairy foods was associated with anovulatory infertility and whether this association differed according to fat content...
  22. pmc A polymorphism in the 3' untranslated region of the gene encoding prostaglandin endoperoxide synthase 2 is not associated with an increase in breast cancer risk: a nested case-control study
    David G Cox
    Program in Genetic and Molecular Epidemiology, Epidemiology Department, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA
    Breast Cancer Res 9:R3. 2007
    ..Polymorphisms in the PTGS2 gene have been associated with various diseases, including inflammatory bowel disease and cancer of the lung, colorectum, and breast...
  23. ncbi Dietary fatty acid intakes and the risk of ovulatory infertility
    Jorge E Chavarro
    Department of Nutrition, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Am J Clin Nutr 85:231-7. 2007
    ..Pharmacologic activation of the peroxisome proliferator-activated receptor gamma (PPAR-gamma) improves ovulatory function in women with polycystic ovary syndrome, and specific dietary fatty acids can affect PPAR-gamma activity...
  24. ncbi Iron intake and risk of ovulatory infertility
    Jorge E Chavarro
    Department of Nutrition and Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA
    Obstet Gynecol 108:1145-52. 2006
    ..To evaluate whether iron supplement use or greater intake of total, heme and nonheme iron is associated with lower risk of ovulatory infertility...
  25. pmc TGFB1 and TGFBR1 polymorphisms and breast cancer risk in the Nurses' Health Study
    David G Cox
    Program in Molecular and Genetic Epidemiology, Epidemiology Department, Harvard School of Public Health, USA
    BMC Cancer 7:175. 2007
    ..Single nucleotide polymorphisms in TGFB1 and a microsatellite in TGFBR1 have been investigated for association with risk of breast cancer, with conflicting results...
  26. ncbi Disclosure of sexual orientation and behavior in the Nurses' Health Study II: results from a pilot study
    Patricia Case
    Fenway Institute, Fenway Community Health, Boston MA 02115, USA
    J Homosex 51:13-31. 2006
    ..To examine disclosure of sexual orientation and response rates in a pilot study of questions on sexual orientation and gender of sexual partners in the Nurses' Health Study II...
  27. ncbi Polymorphisms in O6-methylguanine DNA methyltransferase and breast cancer risk
    Jiali Han
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital, and Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA
    Pharmacogenet Genomics 16:469-74. 2006
    ..We also evaluated the potential interactions between the two polymorphisms and estrogen-related risk factors and cigarette smoking on breast cancer risk...
  28. ncbi Polymorphisms in the ICAM gene locus are not associated with breast cancer Risk
    David G Cox
    Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA
    Cancer Epidemiol Biomarkers Prev 15:178-9. 2006
  29. ncbi Polymorphisms of the AURKA (STK15/Aurora Kinase) Gene and Breast Cancer Risk (United States)
    David G Cox
    Department of Epidemiology, Harvard School of Public Health, 677 Huntington Ave, Boston, MA 02115, USA
    Cancer Causes Control 17:81-3. 2006
    ..29, 95% CI 1.08-1.53, p-heterogeneity = 0.29). These results confirm prior findings that AURKA represents a low penetrance breast cancer susceptibility gene...
  30. ncbi Diet and lifestyle in the prevention of ovulatory disorder infertility
    Jorge E Chavarro
    Department of Nutrition, Harvard School of Public Health, Boston MA 02115, USA
    Obstet Gynecol 110:1050-8. 2007
    ..To evaluate the relation of a dietary pattern and other lifestyle practices to risk of ovulatory disorder infertility...
  31. ncbi Comprehensive association testing of common genetic variation in DNA repair pathway genes in relationship with breast cancer risk in multiple populations
    Christopher A Haiman
    Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
    Hum Mol Genet 17:825-34. 2008
    ..The methods utilized in this study, applied to multiple populations, provide a framework for testing in association studies in diverse populations...
  32. pmc Protein intake and ovulatory infertility
    Jorge E Chavarro
    Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA
    Am J Obstet Gynecol 198:210.e1-7. 2008
    ..The objective of the study was to evaluate whether intake of protein from animal and vegetable origin is associated with ovulatory infertility...
  33. pmc Use of multivitamins, intake of B vitamins, and risk of ovulatory infertility
    Jorge E Chavarro
    Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115, USA
    Fertil Steril 89:668-76. 2008
    ..To examine whether use of multivitamins and intake of specific nutrients in multivitamins is associated with ovulatory infertility...
  34. pmc Fine mapping of 14q24.1 breast cancer susceptibility locus
    Phoebe Lee
    Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Hum Genet 131:479-90. 2012
    ..Therefore, we conclude that rs999737 is an optimal tag SNP for common variants in the 14q24.1 region and thus narrow the candidate variants that should be investigated in follow-up laboratory evaluation...
  35. pmc A prospective study of genetic polymorphism in MPO, antioxidant status, and breast cancer risk
    Chunyan He
    Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA
    Breast Cancer Res Treat 113:585-94. 2009
    ..Further research is needed to confirm these possible associations...
  36. pmc Epidemiologic evidence for a role of telomere dysfunction in cancer etiology
    Jennifer Prescott
    Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
    Mutat Res 730:75-84. 2012
    ..Finally, we conclude with study design considerations as future investigations are needed to elucidate the relationship between telomere length and a number of cancer sites...
  37. pmc Genome-wide association study of relative telomere length
    Jennifer Prescott
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS ONE 6:e19635. 2011
    ..10, such as those for variants at the TERC locus. In general, common genetic variants associated with telomere length homeostasis have been difficult to detect. Potential biological and technical issues are discussed...
  38. pmc A prospective study of dietary carbohydrate quantity and quality in relation to risk of ovulatory infertility
    J E Chavarro
    Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA
    Eur J Clin Nutr 63:78-86. 2009
    ..To evaluate whether the amount or quality of carbohydrate in diet is associated with ovulatory infertility...
  39. pmc Six new loci associated with body mass index highlight a neuronal influence on body weight regulation
    Cristen J Willer
    Genetic Investigation of ANthropometric Traits Consortium
    Nat Genet 41:25-34. 2009
    ..Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity...
  40. pmc Association of ESR1 gene tagging SNPs with breast cancer risk
    Alison M Dunning
    Department of Oncology, University of Cambridge, Cambridge, UK
    Hum Mol Genet 18:1131-9. 2009
    ..The region tagged by SNP rs3020314 contains sequence that is more highly conserved across mammalian species than the rest of intron 4, and it may subtly alter the ratio of two mRNA splice forms...
  41. pmc Caffeinated and alcoholic beverage intake in relation to ovulatory disorder infertility
    Jorge E Chavarro
    Department of Nutrition, Harvard School of Public Health, Boston, MA, USA
    Epidemiology 20:374-81. 2009
    ..However, most of these studies have retrospectively collected information on alcohol and caffeine intake, making the results susceptible to biases...
  42. pmc Newly discovered breast cancer susceptibility loci on 3p24 and 17q23.2
    Shahana Ahmed
    Department of Oncology, University of Cambridge, UK
    Nat Genet 41:585-90. 2009
    ..11, 95% CI = 1.08-1.13, P = 4.1 x 10(-23)) and 17q (rs6504950: per-allele OR = 0.95, 95% CI = 0.92-0.97, P = 1.4 x 10(-8)). Potential causative genes include SLC4A7 and NEK10 on 3p and COX11 on 17q...
  43. pmc A multistage genome-wide association study in breast cancer identifies two new risk alleles at 1p11.2 and 14q24.1 (RAD51L1)
    Gilles Thomas
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
    Nat Genet 41:579-84. 2009
    ..1 (rs999737; P = 1.74 x 10(-7)) localizes to RAD51L1, a gene in the homologous recombination DNA repair pathway. We also confirmed associations with loci on chromosomes 2q35, 5p12, 5q11.2, 8q24, 10q26 and 16q12.1...
  44. pmc The mitochondrial A10398G polymorphism, interaction with alcohol consumption, and breast cancer risk
    Annamaria Pezzotti
    Program in Molecular and Genetic Epidemiology, Epidemiology Department, Harvard School of Public Health, Boston, Massachusetts, United States of America
    PLoS ONE 4:e5356. 2009
    ....
  45. pmc Genome-wide significant predictors of metabolites in the one-carbon metabolism pathway
    Aditi Hazra
    Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA
    Hum Mol Genet 18:4677-87. 2009
    ..40 x 10(-15)). Genome-wide significant loci were not identified for plasma folate. These data reveal new biological candidates and confirm prior candidate genes for plasma homocysteine, plasma vitamin B12 and plasma PLP...
  46. pmc Genetic variation in the estrogen metabolic pathway and mammographic density as an intermediate phenotype of breast cancer
    Jingmei Li
    Karolinska Institutet, Department of Medical Epidemiology and Biostatistics, Stockholm, Sweden
    Breast Cancer Res 12:R19. 2010
    ..In this study, we evaluate the association between mammographic density and genetic variants of the estrogen metabolic pathway...
  47. pmc A prospective study of relative telomere length and postmenopausal breast cancer risk
    Immaculata De Vivo
    Brigham and Women s Hospital Harvard Medical School, Boston, MA 02115, USA
    Cancer Epidemiol Biomarkers Prev 18:1152-6. 2009
    ..07). Our results provide little support for an important role of telomere length, as measured in peripheral blood leukocytes, as a biomarker of breast cancer risk...
  48. pmc Hundreds of variants clustered in genomic loci and biological pathways affect human height
    Hana Lango Allen
    Genetics of Complex Traits, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter EX1 2LU, UK
    Nature 467:832-8. 2010
    ....
  49. pmc Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution
    Iris M Heid
    Regensburg University Medical Center, Department of Epidemiology and Preventive Medicine, Regensburg, Germany
    Nat Genet 42:949-60. 2010
    ..9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions...
  50. pmc Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
    Elizabeth K Speliotes
    Metabolism Initiative and Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA
    Nat Genet 42:937-48. 2010
    ..Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation...
  51. pmc Adult body mass index trajectories and sexual orientation: the Nurses' Health Study II
    Hee Jin Jun
    Channing Laboratory, Brigham and Women s Hospital Harvard Medical School, Boston, Massachusetts, USA
    Am J Prev Med 42:348-54. 2012
    ..Cross-sectional research has documented elevated prevalence of obesity in lesbian and bisexual women relative to heterosexual women, but little is known about disparities in longitudinal patterns in BMI change during adulthood...