Potential differences in breast cancer risk factors based on CYP1A1 MSPI and African-American-specific genotypes

Objectives: Recent studies show that an MspI polymorphism in the 3′-noncoding region of the CYP1A1 gene is associated with breast cancer in African-American women but not in Caucasian women. In addition, an African-American-specific (AAS) polymorphism is located in intron 7 of this gene. We hypothesized that the AAS polymorphism may partially account for this race-specific association and that different environmental risk factor profiles are a function of genotype status. We studied both CYP1A1 polymorphisms to determine if African-American women with these variants have breast cancer risk factor profiles that are different from those of other African-American women. Methods: A case-control analysis was conducted. Cases were 304 African-American patients pathologically diagnosed with breast cancer from 1995 to 1998 who lived in three Tennessee counties. Controls were 305 African-American women without breast cancer, selected through random-digit dialing and frequency matched to cases by age and county. Information on risk factors was collected through telephone interviews. Tumor tissue samples were collected for CYP1A1 genotyping. There were 215 and 188 cases with the MspI and AAS polymorphisms measured respectively. Results: Our study results suggest that some risk factors for breast cancer are dependent upon CYP1A1 genotype. Specifically, low intakes of folate, methionine, vitamin C, and vitamin E appear to increase the risk of breast cancer in individuals with the AAS variant: the odds ratio (OR) estimates and 95% confidence intervals were 2.10 and 0.99-4.44 for folate, 1.96 and 0.91-4.23 for methionine, 2.13 and 1.00-4.53 for vitamin C, and 2.43 and 1.12-5.25 for vitamin E. Such associations are stronger for tumors with both AAS and MspI polymorphisms: the OR estimates increased to >6.00 for all these variables except for vitamin C. Conclusions: This study found that methyldeficient diets and antioxidant vitamins may be related to the risk of breast cancer as a function of the MspI and AAS genotpyes. Our results are preliminary because of a small number of cases with polymorphisms at both sites, but they indicate the need for large-scale epidemiologic studies of both African-American and Caucasian women that include genotype information from controls with more detailed information on risk factors.