Two estrogen-related variants in CYP19A1 and endometrial cancer risk: a pooled analysis in the Epidemiology of Endometrial Cancer Consortium.

Abstract

Common variants in CYP19A1 (the A alleles of rs749292 and rs727479) have been associated with a 10% to 20% increase in circulating estrogen levels in postmenopausal women. We hypothesized that the presence of one or both A alleles in these single nucleotide polymorphisms (SNP) is associated with increased endometrial cancer risk. We tested this hypothesis in a large pooled analysis of 4,998 endometrial cancer cases and 8,285 controls from 10 studies in the Epidemiology of Endometrial Cancer Consortium. The majority of women (>66%) were whites, with smaller proportions of other races and ethnic groups (blacks, Asians, and Latinas) also included in this pooled analysis. Unconditional logistic regression was used to model the association between SNPs/haplotypes and endometrial cancer risk. Carrying the A allele of either of these SNPs was associated with an increased risk of endometrial cancer, with pooled odds ratios per allele of 1.14, 95% confidence interval of 1.09-1.21, and P = 7.1 x 10(-7) for rs749292, and odds ratio per allele of 1.08, 95% confidence interval of 1.02-1.14, and P = 0.009 for rs727479. For rs749292, these associations were generally stronger among women age >or=55 years. For both SNPs, risk increased with increasing body mass index, and for rs727479, this pattern seemed stronger among women age >or=55 years (P interaction = 0.007). The combination of A alleles in the two SNPs, either by direct count or by haplotype analysis, did not increase risk above that observed for the individual SNPs. Our study provides evidence that CYP19A1 genetic variation influences susceptibility to endometrial cancer, particularly among older and obese women.

DOI: 10.1158/1055-9965.EPI-08-0689

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@article{Setiawan2009TwoEV, title={Two estrogen-related variants in CYP19A1 and endometrial cancer risk: a pooled analysis in the Epidemiology of Endometrial Cancer Consortium.}, author={Veronica Wendy Setiawan and Jennifer A Doherty and Xiao Shu and Mohammad R. Akbari and Chu Chen and Immaculata de Vivo and Angela Demichele and Montserrat Garc{\'i}a-Closas and Marc Goodman and Christopher A. Haiman and Susan E . Hankinson and Brian E. Henderson and Pamela L. Horn-Ross and James V Lacey and Lo{\"{i}c Le Le Marchand and Douglas A Levine and Xiaolin Liang and Jolanta Lissowska and Galina Lurie and Monica McGrath and S A Narod and Timothy R. Rebbeck and Giske A Ursin and Noel S Weiss and Yong-Bing Xiang and Hannah Yang and Wei Zheng and Sara H. Olson}, journal={Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, year={2009}, volume={18 1}, pages={242-7} }