Polymorphisms of genes in the lipid metabolism pathway and risk of biliary tract cancers and stones: A population-based case-control study in shanghai, china
Polymorphisms of genes in the lipid metabolism pathway and risk of biliary tract cancers and stones: A population-based case-control study in shanghai, china
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DOI：
10.1158/1055-9965.epi-07-2704
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发表时间：
2008-03-01
影响因子：
3.8
通讯作者：
Hsing, Ann W.
中科院分区：
文献类型：
--
作者：
Andreotti, Gabriella;Chen, Jinbo;Hsing, Ann W.
胆道癌，包括胆囊癌、肝外胆管癌和瓦特壶腹部癌，是一种罕见但致命性极高的恶性肿瘤。胆结石是胆道癌的主要危险因素，与高脂血症有关。中国，我们在上海进行了一项基于人群的病例对照研究，研究了脂代谢途径中五个基因的12个单核苷酸多态与胆道癌和结石风险的关系。其中胆囊癌235例，肝外胆管125例，壶腹癌46例，胆石症880例，对照组779例。受试者完成了面对面的采访并献血。基因分型采用Taq-Man法，DNA取自棕黄色大衣。APOE IVS1+69(Rs440446)和APOB IVS6+360C>(Rs520354)标记的作用仅限于男性。携带APOE IVS1+69 G等位基因的男性患结石的风险是1.7倍[95%可信区间(95%CI)，1.2-2.4]，患胆囊癌的风险是1.8倍(95%CI，1.0-3.3)，患胆管癌的风险是3.7倍(95%CI，2.0-7.0)，患壶腹癌的风险是4倍(95%CI，1.4-12.4)。携带APOB IVS6+360C>；T等位基因的男性患胆道癌的风险是男性的2倍(95%CI，1.2-3.4)。APOB T-T单倍型(APOB IVS6+360C>；T，EX4+56C>；T)与胆道癌的风险增加1.6倍(95%CI，1.1-2.3)。携带LDLR IVS9-30C>；T等位基因(Rs1003723)的男性和女性患胆道癌的风险是男性的1.5倍。我们的发现表明，脂代谢途径中的基因变异会导致胆管结石和癌症的风险，特别是胆管的风险。
Biliary tract cancers, encompassing the gallbladder, extrahepatic bile duct, and ampulla of Vater, are uncommon yet highly fatal malignancies. Gallstones, the primary risk factor for biliary cancers, are linked with hyperlipidemia. We examined the associations of 12 single nucleotide polymorphisms of five genes in the lipid metabolism pathway with the risks of biliary cancers and stones in a population-based case-control study in Shanghai, China. We included 235 gallbladder, 125 extrahepatic bile duct, and 46 ampulla of Vater cancer cases, 880 biliary stone cases, and 779 population controls. Subjects completed an in-person interview and gave blood. Genotyping was conducted by Taq-Man assay using DNA from buffy coats. The effects of APOE IVS1+69 (rs440446) and APOB IVS6+360C>T (rs520354) markers were limited to men. Men carrying the G allele of APOE IVS1+69 had a 1.7-fold risk of stones [95% confidence interval (95% Cl), 1.2-2.4], a 1.8-fold risk of gallbladder cancer (95% Cl, 1.0-3.3), a 3.7-fold risk of bile duct cancer (95% CI, 2.0-7.0), and a 4-fold risk of ampullary cancer (95% CI, 1.4-12.4). Male carriers of the T allele of APOB IVS6+360C>T had a 2-fold risk of bile duct cancer (95% Cl, 1.2-3.4). The APOB T-T haplotype (APOB IVS6+360C>T, EX4+56C>T) was associated with a 1.6-fold risk of bile duct cancer (95% Cl, 1.1-2.3). Male and female carriers of the T allele of LDLR IVS9-30C>T (rs1003723) had a 1.5-fold risk of bile duct cancer. Our findings suggest that gene variants in the lipid metabolism pathway contribute to the risk of biliary tract stones and cancers, particularly of the bile duct.