Catalase (CAT) genotype, dietary antioxidants, and breast cancer risk. Free

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Catalase (CAT) is a heme enzyme that converts hydrogen peroxide into water and oxygen, neutralizing reactive oxygen species (ROS). A C-262T polymorphism exists in the promoter region of the CAT gene with altered transcription factor binding. Because oxidative stress may play an important role in breast carcinogenesis, we hypothesized that the CAT C allele may reduce breast cancer risk, and that risk may be further modified by consumption of fruit and vegetables and specific antioxidants. In a population-based, case-control study (cases=1,037, controls= 1,086), in Nassau and Suffolk Counties, NY, women over 20 years with newly diagnosed, primary in situ or invasive breast cancer were identified between August 1, 1996, and July 31, 1997. Controls were randomly selected from the same counties (RDD for women <65 years and HCFA rosters for those >=65) and frequency-matched to the expected age-distribution of cases by 5-year age groups. In-home interviews included assessment of suspected breast cancer risk factors over the life-course, and a modified Block food frequency questionnaire was used to assess dietary intake 12 months prior to the interview. Genotyping was performed using MALDI-TOF technology. Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI), adjusting for age, BMI, family history of breast cancer, age at first pregnancy, and pack years smoked. In multivariate models, having the common CC genotype was associated with an overall 17% reduction in risk, compared with CT or TT genotypes (OR (95% CI) = 0.83 (0.68-1.00). When intakes of fruits and vegetables and specific dietary antioxidants were dichotomized at the median, inverse associations of risk with CC genotypes were more pronounced among premenopausal women who consumed higher amounts of total fruits and vegetables (OR (95% CI) = 0.60 (0.34-0.98) than lower consumption groups (OR (95% CI) = 1.06 (0.62-1.70), p- value for multiplicative interaction =0.03). Among postmenopausal women, risk associated with the CC genotype did not differ by fruit and vegetable consumption. In this study, the first to evaluate CAT genotypes and breast cancer, the data support the hypothesis that CAT genotype is associated with risk of breast cancer through an oxidative stress mechanism among premenopausal women, perhaps due to a high estrogenic milieu. Furthermore, consumption of fruit and vegetables may enhance inverse associations between CAT genotype and risk among premenopausal women.