Two estrogen-related variants in CYP19A1 and endometrial cancer risk: A pooled analysis in the epidemiology of endometrial cancer consortium Journal Article
| Authors: | 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. Jr; Le Marchand, L.; Levine, D. A.; Liang, X.; Lissowska, J.; Lurie, G.; Mcgrath, M.; Narod, S. A.; Rebbeck, T. R.; Ursin, G.; Weiss, N. S.; Xiang, Y. B.; Yang, H. P.; Zheng, W.; Olson, S. H. |
| Article Title: | 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 × 10<sup>-7</sup> 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. Copyright © 2009 American Association for Cancer Research. |
| Keywords: | adult; controlled study; aged; middle aged; major clinical study; single nucleotide polymorphism; case-control studies; polymorphism, single nucleotide; cancer risk; endometrial neoplasms; endometrium cancer; allele; cancer susceptibility; logistic models; estrogen; estrogens; genetic variability; genotype; alleles; gene frequency; genetic variation; risk factors; obesity; age factors; heterozygote; groups by age; haplotype; body mass; postmenopause; ethnic group; aromatase |
| Journal Title: | Cancer Epidemiology Biomarkers and Prevention |
| Volume: | 18 |
| Issue: | 1 |
| ISSN: | 1055-9965 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2009-01-01 |
| Start Page: | 242 |
| End Page: | 247 |
| Language: | English |
| DOI: | 10.1158/1055-9965.epi-08-0689 |
| PUBMED: | 19124504 |
| PROVIDER: | scopus |
| PMCID: | PMC2668570 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 7" - "Export Date: 30 November 2010" - "CODEN: CEBPE" - "Source: Scopus" |
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