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Molecular Epidemiology of Endometrial Cancer

Endometrial cancer occurs in the inner lining of the uterus. For a number of years, we have been studying the environmental and genetic factors that may influence the development of endometrial cancer. Manuscripts describing the association of potential risk factors, such as diabetes, NSAID use, and long term use of postmenopausal estrogen and progestin have been published. Dr. Chen and her team have also published results describing the associations between endometrial cancer risk and genetic polymorphisms of some of genes that encode for enzymes that are involved in the biosynthesis or catabolism of estrogens; the response to steroid hormones; and the repair of DNA damages generated during estrogen exposure.

Publications

1)   Sakoda LC, Loomis MM, Doherty JA, Neuhouser ML, Barnett MJ, Thornquist MD, Weiss NS, Goodman GE, Chen C. Chromosome 15q24-25.1 variants, diet, and lung cancer susceptibility in cigarette smokers. Cancer Causes Control, 22(3):449-61, 2011. PMCID: PMC3042523.

2)   Sakoda LC, Loomis ML, Doherty JA, Julianto L, Barnett, MJ, Neuhouser ML, Thornquist   MD, Weiss NS, Goodman GE, Chen C. Germ line variation in nucleotide excision repair genes and lung cancer risk in smokers.  Int J Mol Epidemio Genet, 3(1):1-17, 2012. PMCID: PMC3316453.

3)   Doherty JA, Sakoda LC, Loomis MM, Barnett, MJ, Julianto L, Thornquist MD, Neuhouser ML, Weiss NS, Goodman GE, Chen C. DNA repair genotype and lung cancer risk in the Beta-Carotene and Retinal Efficacy Trial.  Int J Mol Epidemio Genet. 2013; 4(1):11-34. PMID: 23565320, PMCID: PMC3612452.


Genome-Wide Association Study of Endometrial Cancer (E2C2 GWAS)

Endometrial cancer is the fourth most common cancer among women in the United States. This GWAS study includes five cohort studies and six case-control studies that have collected biospecimens, by far the largest international collaborative study of this cancer. It evaluated the association between the risk of endometrial cancer and single nucleotide polymorphisms on the genome-wide level as well as the impact of gene and environment interaction on endometrial cancer risk. The overall goal is to determine whether certain genotypes are predictive of future endometrial cancer risk, and whether the genotypes interact with established endometrial risk factors.

Selected publications on endometrial cancer from collaboration with E2C2 and WHI investigators

1) Olson SH, et al. Maximizing resources to study an uncommon cancer: E2C2 – Epidemiology of Endometrial Cancer Consortium. Cancer Causes and Control, 20:491-496, 2009. PMCID: PMC2868317.

2) Setiawan VW, et al. Two estrogen-related variants in CYP19A1 and endometrial cancer risk: A pooled analysis in the Epidemiology of Endometrial Cancer Consortium. Cancer Epidemiol Biomarkers Prev, 18:242-247, 2009. PMCID: PMC2668570.

3) Lurie G et al. PLoS One. 2011; 6(2):e16756. The obesity-associated polymorphisms FTO rs9939609 and MC4R rs17782313 and endometrial cancer risk in non-Hispanic white women. PLoS One, 6(2):e16756, 2011. PMCID: PMC3035652.

4) Setiawan VW et al. Am J Epidemiol. 2012; 176(4):269-78. Age at last birth in relation to risk of endometrial cancer: pooled analysis in the Epidemiology of Endometrial Cancer Consortium. PMID:22831825, PMCID:PMC3491967.

5) Setiawan VW et al. J Clin Oncol. 2013; 31(20):2607-8. Type I and II endometrial cancer: have they different risk factors? PMID:23733771, PMCID: PMC3699726.

6) De Vivo I et al. Human Genet. 2014; 133(2):211-24. Genome-wide association study of endometrial cancer in E2C2. PMID:24096698, PMCID:PMC3898362.

7) Chen MM et al. PLOS One. 2014; 9(5):e97045. Exome-wide association study of endometrial cancer in a multiethnic population. PLOS One. 2014; 9(5):e97045. PMID: 24810602, PMCID: PMC4014590.

8) Luo J et al. Br J Cancer. 2014; 111(7):1432-9. Association between diabetes, diabetes treatment and risk of developing endometrial cancer. PMID:25051408, PMCID:PMC4183842.

9) Felix AS et al. Int J Cancer. 2015; 136(5):E410-22. Intrauterine devices and endometrial cancer risk: a pooled analysis of the Epidemiology of Endometrial Cancer Consortium. PMID: 25242594, PMCID: PMC4267918.

10) Cote ML et al. Cancer Causes Control. 2015; 26(2):287-96. Risk factors for endometrial cancer in black and white women: a pooled analysis from the epidemiology of endometrial cancer consortium (E2C2). PMID:25534916,PMCID: PMC4528374