Two estrogen-related variants in CYP19A1 and endometrial cancer risk: A pooled analysis in the epidemiology of endometrial cancer consortium

Veronica Wendy Setiawan, Jennifer A. Doherty, Xiao Ou Shu, Mohammad R. Akbari, Chu Chen, Immaculata De Vivo, Angela DeMichele, Montserrat Garcia-Closas, Marc T. Goodman, Christopher A. Haiman, Susan E. Hankinson, Brian E. Henderson, Pamela L. Horn-Ross, James V. Lacey, Loic Le Marchand, Douglas A. Levine, Xiaolin Liang, Jolanta Lissowska, Galina Lurie, Monica McGrathSteven A. Narod, Timothy R. Rebbeck, Giske Ursin, Noel S. Weiss, Yong Bing Xiang, Hannah P. Yang, Wei Zheng, Sara H. Olson

Research output: Contribution to journalArticle

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 × 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 ≥55 years. For both SNPs, risk increased with increasing body mass index, and for rs727479, this pattern seemed stronger among women age ≥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.

Original languageEnglish (US)
Pages (from-to)242-247
Number of pages6
JournalCancer Epidemiology Biomarkers and Prevention
Volume18
Issue number1
DOIs
StatePublished - Jan 1 2009
Externally publishedYes

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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    Setiawan, V. W., Doherty, J. A., Shu, X. O., Akbari, M. R., Chen, C., De Vivo, I., DeMichele, A., Garcia-Closas, M., Goodman, M. T., Haiman, C. A., Hankinson, S. E., Henderson, B. E., Horn-Ross, P. L., Lacey, J. V., Le Marchand, L., Levine, D. A., Liang, X., Lissowska, J., Lurie, G., ... Olson, S. H. (2009). Two estrogen-related variants in CYP19A1 and endometrial cancer risk: A pooled analysis in the epidemiology of endometrial cancer consortium. Cancer Epidemiology Biomarkers and Prevention, 18(1), 242-247. https://doi.org/10.1158/1055-9965.EPI-08-0689