A case -control study was performed to assess the potential influence of CYP19 Arg 264 Cys and CYP1B1 Leu 432 Val polymorphisms on breast cancer risk in a series of Korean breast cancer patients and controls. The results suggest that the CYP19 Arg 264 Cys polymorphism modifies breast cancer risk (OR ¼ 1.5, 95% CI ¼ 1.1 -2.2), especially in association with alcohol consumption (P for interaction ¼ 0.04), whereas the CYP1B1 Leu 432 Val polymorphism appears to play no role here. Breast cancer is the second most frequent cancer in Korean women and its incidence is increasing (Yoo et al, 1998). Lifetime cumulative exposure to oestrogens is known as the most important risk factor for breast cancer (Yager, 2000). A variety of different enzymes are involved in the synthesis of oestrogen from cholesterol and further metabolism of oestrogen (Thompsen and Ambrosone, 2000). Polymorphisms of genes encoding for these proteins are regarded as the candidates for elevated breast cancer risk.The CYP19 gene encodes aromatase, which catalyses the formation of oestrogens from testosterone and androstenedione. To date, several polymorphisms have been found in the CYP19 gene (i.e. Polymeropulous et al, 1991;Sourdaine et al, 1994;Siegelmann-Danieli and Buetow, 1999;Healey et al, 2000;Miyoshi et al, 2000). One of these, a C-to-T variation in exon 7 resulting in an Arg 264 Cys amino-acid exchange, has been shown to be very common in Asians (Watanabe et al, 1997;Miyoshi et al, 2000) and could thus be an important modifier of breast cancer risk in this ethnic group.The CYP1B1 enzyme is known to be involved in the formation of 4-hydroxyoestradiol, which is a catechol metabolite of oestrogen (Hayes et al, 1996). A C-to-G variation in exon 3 of the CYP1B1 gene results in a Leu 432 Val amino-acid exchange. The Leu/Leu genotype has been associated with increased breast cancer risk in an Asian population (Zheng et al, 2000) but controversial results have been reported as well (Bailey et al, 1998;Watanabe et al, 2000).In this study, we have evaluated the potential influence of CYP19 Arg 264 Cys and CYP1B1 Leu 432 Val polymorphisms on the breast cancer risk among Korean women as an extension of our previous work in this study population (Park et al, 2000;Yim et al, 2001).
MATERIALS AND METHODS
Study subjectsThe criteria of subject selection and details of data collection on lifestyle have been described elsewhere (Park et al, 2000;Yim et al, 2001). Eligible study population consisted of 389 incident breast cancer cases and 346 controls with no other known cancer or systemic disease, admitted in 1995 -2001 to three teaching hospitals located in Seoul, Korea (Seoul National University Hospital, Borame Hospital, and Asan Medical Center). Each patient was frequency-matched to one control in the following age groups : under 30, 30 -34, 35 -39, 40 -44, 45 -49, 50 -54, 55 -59, 60 -69, and over 70 years; 288 cases and 288 controls were selected and genotyped for CYP19. Informed consents were obtained at the time of blood withdrawal. Information on demogr...
