SULT1A1 Genotype, Active and Passive Smoking, and Breast Cancer Risk by Age 50 Years in a German Case-control Study

Introduction: Sulfotransferase 1A1 (encoded by SULT1A1) is involved in the metabolism of procarcinogens such as heterocyclic amines and polycyclic aromatic hydrocarbons, both of which are present in tobacco smoke. We recently reported a differential effect of N-acetyltransferase (NAT) 2 genotype on the association between active and passive smoking and breast cancer. Additional investigation of a common SULT1A1 genetic polymorphism associated with reduced enzyme activity and stability might therefore provide deeper insight into the modification of breast cancer susceptibility.

Methods: We conducted a population-based case-control study in Germany. A total of 419 patients who had developed breast cancer by age 50 years and 884 age-matched control individuals, for whom risk factor information and detailed smoking history were available, were included in the analysis. Genotyping was performed using a fluorescence-based melting curve analysis method. Multivariate logistic regression analysis was used to estimate breast cancer risk associated with the SULT1A1 Arg213His polymorphism alone and in combination with NAT2 genotype in relation to smoking.

Results: The overall risk for breast cancer in women who were carriers of at least one SULT1A1*2 allele was not significantly different from that for women with the SULT1A1*1/*1 genotype (adjusted odds ratio 0.83, 95% confidence interval 0.66-1.06). Risk for breast cancer with respect to several smoking variables did not differ substantially between carriers of the *2 allele and noncarriers. However, among NAT2 fast acetylators, the odds ratio associated with passive smoking only (3.23, 95% confidence interval 1.05-9.92) was elevated in homozygous carriers of the SULT1A1*1 allele but not in carriers of the SULT1A1*2 allele (odds ratio 1.28, 95% confidence interval 0.50-3.31).

Conclusion: We found no evidence that the SULT1A1 genotype in itself modifies breast cancer risk associated with smoking in women up to age 50 years. In combination with NAT2 fast acetylator status, however, the SULT1A1*1/*1 genotype might increase breast cancer risk in women exposed to tobacco smoke.