Sulfotransferase 1A1 polymorphism, endogenous estrogen exposure, well-donemeat intake, and breast cancer risk

Sulfotransferase (SULT) 1A1 is involved in the inactivation of estrogens an d bioactivation of heterocyclic amines and polycyclic aromatic hydrocarbons . A G -->A transition at codon 213 (CGC/Arg to CAC/His) of the SULT1A1 gene was reported recently, and individuals homozygous for the His allele have a substantially lower activity of this enzyme than those with other genotyp es, We hypothesized that the His allele may be a risk factor for breast can cer, particularly among women who had risk factors related to higher endoge nous estrogen exposure. This hypothesis was investigated in a case-control study conducted in a cohort of postmenopausal Iowa women who completed a ma iled questionnaire in 1986 on lifestyle factors including information on ma jor breast cancer risk factors. DNA samples and information related to well -done meat intake were obtained from breast cancer cases diagnosed between 1992 and 1994 and a random sample of cancer-free cohort members. Multivaria te analysis was performed on data from 156 cases and 332 controls who donat ed a blood sample. The frequency of the His allele was 41.6% in cases and 3 4.1% in controls (P = 0.03), and the risk of breast cancer was increased wi th the number of His alleles (P for trend = 0.02), Compared with women with the Arg/Arg genotype, an 80% elevated risk was observed among women homozy gous for the His allele (95% confidence interval, 1.0-3.2; P = 0.04), This positive association was more pronounced among women who drank alcohol and had a high body mass index, early age at menarche, and late age at menopaus e, factors related to high endogenous estrogen exposure, than among those w ho did not have these risk factors. The risk of breast cancer was elevated with increasing doneness level of red meat intake among women with the Arg/ Arg genotype (P for trend, 0.01) or the Arg/His genotype (P for trend, 0.10 ), whereas this association was not evident for women with the His/His geno type, The results from this study suggest that homozygosity for the SULT1A1 His(213) allele may be a risk factor for breast cancer, and its effect may be modified by the exposure level of endogenous estrogens and heterocyclic amines.