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KMID : 1137020110220020110
Journal of Gynecologic Oncology
2011 Volume.22 No. 2 p.110 ~ p.119
Combined effect of CYP1B1, COMT, GSTP1, and MnSOD genotypes and risk of postmenopausal breast cancer
Cerne Jasmina-Ziva

Pohar-Perme Maja
Novakovic Srdjan
Frkovic-Grazio Snjezana
Stegel Vida
Gersak Ksenija
Abstract
Objective: Estrogen plays a key role in breast cancer development and functionally relevant genetic variants within the estrogen metabolic pathway are prime candidates for a possible association with breast cancer risk. We investigated the independent and the combined effects of commonly occurring polymorphisms in four genes encoding key proteins of estrogen metabolic pathway on their potential contribution to breast cancer risk.

Methods: We studied 530 breast cancer cases and 270 controls of the same age and ethnicity participating in a case¡ªcontrol study of postmenopausal women. Genotyping was conducted for CYP1B1 (rs1056836), COMT (rs4680), GSTP1 (rs1695), and MnSOD (rs4880) polymorphisms by polymerase chain reaction based restriction fragment length polymorphism and TaqMan allelic discrimination method. Adjusted ORs and 95% CIs were calculated using logistic regression.

Results: None of the 4 genetic variants examined contributed to breast cancer risk individually. When the combined effects of the risk genotypes were investigated, significant associations were observed among women with two high¡ªrisk genotypes in CYP1B1 and COMT (OR, 2.0; 95% CI, 1.1 to 3.5) and two high¡ªrisk genotypes in COMT and MnSOD (OR, 2.0; 95% CI, 1.0 to 3.8), compared to those with low¡ªrisk genotypes.

Conclusion: Our results suggest that individual susceptibility to breast cancer incidence may be increased by combined effects of the high¡ªrisk genotypes in CYP1B1, COMT, and MnSOD estrogen metabolic genes.
KEYWORD
Breast neoplasms, Estrogen metabolism, Combined polymorphisms, Association study
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