ENDOMETRIAL CANCER AND CYP1A1, GSTM1 AND POLYMORPHISMS

Summary

Principal Investigator: Noel Weiss
Abstract: DESCRIPTION: (Applicant's Description) Women who smoke cigarettes have about half the risk of endometrial cancer of non-smokers. Female smokers have been observed to have an increase in 2-hydroxylation of estrogens, and this increased 2-hydroxylation has been suggested as a mechanism to explain the apparent antiestrogenic effect of cigarette smoke. Polymorphisms in several genes involved in metabolizing potential carcinogens in cigarette smoke have been related to an increased risk of lung cancer. One of these genes is also involved in 2-hydroxylation of estrogens. Thus, it might be anticipated that women who have the high-risk genotypes, in terms of lung cancer, would have a reduced risk of a condition such as endometrial cancer, whose incidence is reduced by cigarette smoking. However, in a recent small case-control study, a strong, positive relationship between the presence of some of the polymorphisms in these genes and endometrial cancer risk was reported. In our proposed population-based case-control study, we will explore whether polymorphisms in some of these genes are associated with endometrial cancer risk. The genes of interest are: cytochrome P450 1A1 (CYP1A1), glutathione-S-transferases M1 (GSTM1) and T1 (GSTT1), and catechol-O-methyltransferase (COMT). Cases and controls will be drawn from our funded study of continuous combined hormone replacement therapy and endometrial cancer. Cases are women ages 50-69 years with incident endometrial cancer diagnosed between 6/l/97 and 7/31/00, who reside in western Washington. Controls are women recruited through random-digit dialing (ages 50-64 years) and Health Care Financing Administration files (ages 65-69 years), who reside in the same geographic area. In the proposed study, 175 cases and 175 controls will be asked to provide a blood specimen at the time of interview. Using purified DNA from these blood samples, the genotypes of interest will be assayed using PCR and RFLPs. Differences in the distributions of genotypes between cases and controls will be assessed in the whole study population, as well as in sub-groups of women defined by cigarette smoking history and use of hormone replacement therapy (HRT). Since endometrial cancer is strongly hormone-related, the results of this study could have relevance for other, more common cancers whose relation to hormones is not so straightforward. Additionally, this information potentially could be used to predict a woman's sensitivity to the carcinogenic effects of HRT, and thus bear on a woman's decision regarding long-term use of HRT.
Funding Period: 1998-09-30 - 2001-10-31
more information: NIH RePORT

Top Publications

  1. pmc Exome-wide association study of endometrial cancer in a multiethnic population
    Maxine M Chen
    Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, Boston, Massachusetts, United States of America
    PLoS ONE 9:e97045. 2014
  2. ncbi Genetic factors in catechol estrogen metabolism in relation to the risk of endometrial cancer
    Jennifer A Doherty
    Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, P O Box 19024 M4 C308, Seattle, WA 98109 1024, USA
    Cancer Epidemiol Biomarkers Prev 14:357-66. 2005
  3. ncbi Interindividual variation in nucleotide excision repair genes and risk of endometrial cancer
    Jocelyn M Weiss
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, Occupational and Environmental Epidemiology Branch, 6120 Executive Boulevard, EPS 8123, MSC 7240, Rockville, MD 20852, USA
    Cancer Epidemiol Biomarkers Prev 14:2524-30. 2005
  4. ncbi Nucleotide excision repair genotype and the incidence of endometrial cancer: effect of other risk factors on the association
    Jocelyn M Weiss
    Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, WA, USA
    Gynecol Oncol 103:891-6. 2006
  5. pmc Two estrogen-related variants in CYP19A1 and endometrial cancer risk: a pooled analysis in the Epidemiology of Endometrial Cancer Consortium
    Veronica Wendy Setiawan
    Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
    Cancer Epidemiol Biomarkers Prev 18:242-7. 2009
  6. pmc Maximizing resources to study an uncommon cancer: E2C2--Epidemiology of Endometrial Cancer Consortium
    Sara H Olson
    Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, 307 East 63 Street, New York, NY 10065, USA
    Cancer Causes Control 20:491-6. 2009
  7. pmc The obesity-associated polymorphisms FTO rs9939609 and MC4R rs17782313 and endometrial cancer risk in non-Hispanic white women
    Galina Lurie
    Cancer Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu, Hawaii, United States of America
    PLoS ONE 6:e16756. 2011
  8. pmc Polymorphisms in nucleotide excision repair genes and endometrial cancer risk
    Jennifer A Doherty
    Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
    Cancer Epidemiol Biomarkers Prev 20:1873-82. 2011

Scientific Experts

  • Jocelyn M Weiss
  • Sara Olson
  • Galina Lurie
  • Jennifer A Doherty
  • Chu Chen
  • Noel S Weiss
  • Maxine M Chen
  • Jolanta Lissowska
  • Immaculata De Vivo
  • Xiaolin Liang
  • Susan E Hankinson
  • Brian E Henderson
  • Loic Le Marchand
  • Xiao Ou Shu
  • Hannah P Yang
  • Timothy R Rebbeck
  • Veronica Wendy Setiawan
  • Mary Anne Rossing
  • Christopher Haiman
  • Marta Crous-Bou
  • Frederick Schumacher
  • Patricia Hartge
  • Jennifer Doherty
  • Stacey Petruzella
  • Linda S Cook
  • Lingeng Lu
  • Harvey Risch
  • Jennifer Prescott
  • Christine M Friedenreich
  • Constance Chen
  • Irene Orlow
  • Peter Kraft
  • Amanda Black
  • Xin Sheng
  • Carlotta Sacerdote
  • Loreall Pooler
  • Silvia Polidoro
  • David J Hunter
  • Nicolas Wentzensen
  • David Van Den Berg
  • Herbert Yu
  • Louise Brinton
  • Veronica W Setiawan
  • Stephen Chanock
  • Lucy Xia
  • Lue Ping Zhao
  • Melissa M Loomis
  • Lori C Sakoda
  • Wenhong Fan
  • Sherianne Fish
  • Steven A Narod
  • James V Lacey
  • Douglas A Levine
  • Marc T Goodman
  • Monica McGrath
  • Christopher A Haiman
  • Montserrat Garcia-Closas
  • Wei Zheng
  • Mohammad R Akbari
  • Yong Bing Xiang
  • Angela DeMichele
  • Giske Ursin
  • Pamela L Horn-Ross
  • Lynda F Voigt
  • Perry J Thornton
  • Robert J Freeman
  • John R Houck
  • Douglas A Dightman
  • Stephen M Schwartz

Detail Information

Publications8

  1. pmc Exome-wide association study of endometrial cancer in a multiethnic population
    Maxine M Chen
    Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, Boston, Massachusetts, United States of America
    PLoS ONE 9:e97045. 2014
    ..No variants reached global significance in the study, suggesting that more power is needed to detect modest associations between rare genetic variants and risk of EC. ..
  2. ncbi Genetic factors in catechol estrogen metabolism in relation to the risk of endometrial cancer
    Jennifer A Doherty
    Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, P O Box 19024 M4 C308, Seattle, WA 98109 1024, USA
    Cancer Epidemiol Biomarkers Prev 14:357-66. 2005
    ....
  3. ncbi Interindividual variation in nucleotide excision repair genes and risk of endometrial cancer
    Jocelyn M Weiss
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, Occupational and Environmental Epidemiology Branch, 6120 Executive Boulevard, EPS 8123, MSC 7240, Rockville, MD 20852, USA
    Cancer Epidemiol Biomarkers Prev 14:2524-30. 2005
    ..58; 95% CI, 0.35-0.96). Our data suggest that interindividual variation in XPA and XPC influences a woman's risk of endometrial cancer...
  4. ncbi Nucleotide excision repair genotype and the incidence of endometrial cancer: effect of other risk factors on the association
    Jocelyn M Weiss
    Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, WA, USA
    Gynecol Oncol 103:891-6. 2006
    ..Certain nucleotide excision repair (NER) genotypes appear to be associated with an altered risk of endometrial cancer. These associations could be modified by characteristics and exposures that themselves influence risk of disease...
  5. pmc Two estrogen-related variants in CYP19A1 and endometrial cancer risk: a pooled analysis in the Epidemiology of Endometrial Cancer Consortium
    Veronica Wendy Setiawan
    Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
    Cancer Epidemiol Biomarkers Prev 18:242-7. 2009
    ..Our study provides evidence that CYP19A1 genetic variation influences susceptibility to endometrial cancer, particularly among older and obese women...
  6. pmc Maximizing resources to study an uncommon cancer: E2C2--Epidemiology of Endometrial Cancer Consortium
    Sara H Olson
    Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, 307 East 63 Street, New York, NY 10065, USA
    Cancer Causes Control 20:491-6. 2009
    ..Overall, the consortium promises to provide an important means of furthering our knowledge about this cancer...
  7. pmc The obesity-associated polymorphisms FTO rs9939609 and MC4R rs17782313 and endometrial cancer risk in non-Hispanic white women
    Galina Lurie
    Cancer Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu, Hawaii, United States of America
    PLoS ONE 6:e16756. 2011
    ....
  8. pmc Polymorphisms in nucleotide excision repair genes and endometrial cancer risk
    Jennifer A Doherty
    Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
    Cancer Epidemiol Biomarkers Prev 20:1873-82. 2011
    ..Certain estrogen metabolites can form bulky DNA adducts, which are removed via nucleotide excision repair (NER), and the ability to carry out this repair might be related to endometrial cancer risk...