Lilla Carmen, Risch Angela, Kropp Silke, Chang-Claude Jenny
Division of Clinical Epidemiology, German Cancer Research Center, Heidelberg, Germany.
Breast Cancer Res. 2005;7(2):R229-37. doi: 10.1186/bcr976. Epub 2005 Jan 14.
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.
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.
The overall risk for breast cancer in women who were carriers of at least one SULT1A12 allele was not significantly different from that for women with the SULT1A11/1 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 SULT1A11 allele but not in carriers of the SULT1A12 allele (odds ratio 1.28, 95% confidence interval 0.50-3.31).
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.
磺基转移酶1A1（由SULT1A1编码）参与杂环胺和多环芳烃等致癌物的代谢，这两种物质都存在于烟草烟雾中。我们最近报告了N - 乙酰转移酶（NAT）2基因型对主动和被动吸烟与乳腺癌关联的差异影响。因此，对一种与酶活性和稳定性降低相关的常见SULT1A1基因多态性进行进一步研究，可能会更深入地了解乳腺癌易感性的改变。
我们在德国进行了一项基于人群的病例对照研究。分析纳入了419名50岁前患乳腺癌的患者以及884名年龄匹配的对照个体，这些对照个体有危险因素信息和详细的吸烟史。使用基于荧光的熔解曲线分析方法进行基因分型。多因素逻辑回归分析用于估计与SULT1A1 Arg213His多态性单独以及与NAT2基因型联合相关的吸烟相关乳腺癌风险。
至少携带一个SULT1A12等位基因的女性患乳腺癌的总体风险与SULT1A11/1基因型的女性无显著差异（调整后的优势比为0.83，95%置信区间为0.66 - 1.06）。2等位基因携带者和非携带者在几个吸烟变量方面的乳腺癌风险没有实质性差异。然而，在NAT2快速乙酰化者中，仅被动吸烟相关的优势比（3.23，95%置信区间为1.05 - 9.92）在SULT1A11等位基因的纯合携带者中升高，但在SULT1A12等位基因的携带者中未升高（优势比为1.28，95%置信区间为0.50 - 3.31）。
我们没有发现证据表明SULT1A1基因型本身会改变50岁及以下女性吸烟相关的乳腺癌风险。然而，与NAT2快速乙酰化状态相结合，SULT1A1*1/*1基因型可能会增加接触烟草烟雾女性的乳腺癌风险。
