J Gynecol Oncol.  2011 Jun;22(2):110-119. 10.3802/jgo.2011.22.2.110.

Combined effect of CYP1B1, COMT, GSTP1, and MnSOD genotypes and risk of postmenopausal breast cancer

• Cerne JZ
• Pohar-Perme M
• Novakovic
• Frkovic-Grazio S
• Stegel V
• Gersak K

• KMID: 2288575
• DOI: http://doi.org/10.3802/jgo.2011.22.2.110

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-control 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-risk genotypes in CYP1B1 and COMT (OR, 2.0; 95% CI, 1.1 to 3.5) and two high-risk genotypes in COMT and MnSOD (OR, 2.0; 95% CI, 1.0 to 3.8), compared to those with low-risk genotypes.
CONCLUSION
Our results suggest that individual susceptibility to breast cancer incidence may be increased by combined effects of the high-risk genotypes in CYP1B1, COMT, and MnSOD estrogen metabolic genes.

Keyword

Breast neoplasms; Estrogen metabolism; Combined polymorphisms; Association study

MeSH Terms

Aryl Hydrocarbon Hydroxylases
Breast
Breast Neoplasms
Case-Control Studies
Discrimination (Psychology)
Electrolytes
Estrogens
Female
Genotype
Humans
Incidence
Metabolic Networks and Pathways
Polymerase Chain Reaction
Polymorphism, Restriction Fragment Length
Proteins
Aryl Hydrocarbon Hydroxylases
Electrolytes
Estrogens
Proteins

Figure

• 

  Fig. 1 A schematic presentation of enzymes with known gene polymorphisms involved in estrogen biosynthesis and metabolism. Modified from [12] with permission from Elsevier.

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