Kotnis A, Kannan S, Sarin R, Mulherkar R
Genetic Engineering Unit, Advanced Centre for Treatment, Research & Education in Cancer, Tata Memorial Centre, Navi Mumbai, India.
Br J Cancer. 2008 Oct 21;99(8):1340-7. doi: 10.1038/sj.bjc.6604683.
Cytosolic sulphotransferase SULT1A1 plays a dual role in the activation of some carcinogens and inactivation of others. A functional polymorphism leading to Arg(213)His substitution (SULT1A12) affects its catalytic activity and thermostability. To study the association of SULT1A12 polymorphism with tobacco-related cancers (TRCs), a case-control study comprising 132 patients with multiple primary neoplasm (MPN) involving TRC and 198 cancer-free controls was carried out. One hundred and thirteen MPN patients had at least one cancer in upper aerodigestive tract including lung (UADT-MPN). SULT1A12 showed significant risk association with UADT-MPN (odds ratio (OR)=5.50, 95% confidence interval (CI): 1.09, 27.7). Meta-analysis was conducted combining the data with 34 published studies that included 11 962 cancer cases and 14 673 controls in diverse cancers. The SULT1A12 revealed contrasting risk association for UADT cancers (OR=1.62, 95% CI: 1.12, 2.34) and genitourinary cancers (OR=0.73, 95% CI: 0.58, 0.92). Furthermore, although SULT1A1*2 conferred significant increased risk of breast cancer to Asian women (OR=1.91, 95% CI: 1.08, 3.40), it did not confer increased risk to Caucasian women (OR=0.92, 95% CI: 0.71, 1.18). Thus risk for different cancers in distinct ethnic groups could be modulated by interaction between genetic variants and different endogenous and exogenous carcinogens.
胞质磺基转移酶SULT1A1在某些致癌物的激活和其他致癌物的失活中起双重作用。导致精氨酸(213)组氨酸替代的功能性多态性(SULT1A12)会影响其催化活性和热稳定性。为了研究SULT1A12多态性与烟草相关癌症(TRC)的关联,开展了一项病例对照研究,该研究包括132例患有涉及TRC的多原发性肿瘤(MPN)的患者和198例无癌对照。113例MPN患者在上呼吸消化道至少患有一种癌症,包括肺癌(UADT-MPN)。SULT1A12与UADT-MPN显示出显著的风险关联(优势比(OR)=5.50,95%置信区间(CI):1.09,27.7)。进行了荟萃分析,将这些数据与34项已发表的研究相结合,这些研究包括11962例癌症病例和14673例不同癌症的对照。SULT1A12显示出与UADT癌症(OR=1.62,95%CI:1.12,2.34)和泌尿生殖系统癌症(OR=0.73,95%CI:0.58,0.92)形成对比的风险关联。此外,尽管SULT1A1*2使亚洲女性患乳腺癌的风险显著增加(OR=1.91,95%CI:1.08,3.40),但并未使白种女性患癌风险增加(OR=0.92,95%CI:0.71,1.18)。因此,不同种族群体中不同癌症的风险可能受到基因变异与不同内源性和外源性致癌物之间相互作用的调节。