Variants in hormone-related genes and the risk of biliary tract cancers and stones: a population-based study in China
Variants in hormone-related genes and the risk of biliary tract cancers and stones: a population-based study in China
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DOI：
10.1093/carcin/bgp024
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发表时间：
2009-04-01
期刊：
影响因子：
4.7
通讯作者：
Hsing, Ann W.
中科院分区：
文献类型：
--
作者：
Park, Sue K.;Andreotti, Gabriella;Hsing, Ann W.
胆道癌，包括胆囊癌、肝外胆管癌和乏特壶腹癌，是一种罕见但往往致命的恶性肿瘤。激素相关因素，包括产次、口服避孕药使用、肥胖和胆结石，都与这些癌症的病因有关。为了进一步阐明激素在胆道癌和胆结石中的作用，我们在中国上海进行了一项基于人群的病例对照研究，对参与类固醇激素生物合成、代谢和转运的9个基因中的18个单核苷酸多态性（SNP）进行了基因分型。本研究纳入了完成访谈并提供血液的受试者，共计411例胆道癌和893例胆结石患者以及786名健康上海居民。CYP1A1 IVS 1 + 606（rs 2606345）T等位基因与胆囊癌[比值比（OR）= 2.0，95%可信区间（CI）1.3-3.0]和胆管癌相关CYP 1A 1 Ex 7 + 131（rs 1048943）G等位基因与壶腹癌相关（OR = 1.8，95%CI = 1.1-3.1），而与壶腹癌相关（OR = 2.9，95%CI = 1.5-5.4）。在考虑每个基因内SNP的多重比较后，CYP 1A 1与胆囊癌（P = 0.004）和乏特壶腹癌（P = 0.01）显著相关，但与胆管癌（P = 0.06）边缘。CYP 1A 1 IVS 1 + 606对胆囊癌的作用在非肥胖者（体重指数< 23）中更为明显（OR = 3.3，95%CI = 1.8-6.1; P交互作用= 0.001）。在服用口服避孕药的女性中，SHBG Ex 8 + 6（rs6259）对胆囊癌（OR = 6.7，95% CI = 2.2-20.5; P相互作用= 0.001）和结石（OR = 2.3，95% CI = 1.1-4.9; P相互作用= 0.05）的影响具有统计学显著性。我们的研究结果表明，胆道癌相关基因的常见变异可能通过调节激素代谢而增加胆道癌和结石的风险。
Biliary tract cancers, encompassing gallbladder, extrahepatic bile duct and ampulla of Vater cancers, are uncommon but often fatal malignancies. Hormone-related factors, including parity, oral contraceptive use, obesity, and gallstones, have been implicated in the etiology of these cancers. To further clarify the role of hormones in biliary tract cancers and biliary stones, we genotyped 18 single-nucleotide polymorphisms (SNPs) in nine genes involved in steroid hormone biosynthesis, metabolism and transport in a population-based case-control study in Shanghai, China. This study included subjects who completed an interview and provided blood, which totaled 411 biliary tract cancer and 893 biliary stone patients and 786 healthy Shanghai residents. The CYP1A1 IVS1 + 606 (rs2606345) T allele was associated with gallbladder [odds ratio (OR) = 2.0, 95% confidence interval (CI), 1.3-3.0] and bile duct cancers (OR = 1.8, 95% CI = 1.1-3.1), whereas the CYP1A1 Ex7 + 131 (rs1048943) G allele was associated with ampulla of Vater cancer (OR = 2.9, 95% CI = 1.5-5.4). After taking into account multiple comparisons for SNPs within each gene, CYP1A1 was significantly associated with gallbladder (P = 0.004) and ampulla of Vater cancers (P = 0.01), but borderline with bile duct cancer (P = 0.06). The effect of CYP1A1 IVS1 + 606 on gallbladder cancer was more pronounced among non-obese (body mass index < 23) (OR = 3.3, 95% CI = 1.8-6.1; P interaction = 0.001). Among women taking oral contraceptives, the effect of SHBG Ex8 + 6 (rs6259) on gallbladder cancer (OR = 6.7, 95% CI = 2.2-20.5; P interaction = 0.001) and stones (OR = 2.3, 95% CI = 1.1-4.9; P-interaction = 0.05) was statistically significant. Our findings suggest that common variants in hormone-related genes contribute to the risk of biliary tract cancers and stones, possibly by modulating hormone metabolism.