PNPLA3 I148M (rs738409) genetic variant is associated with hepatocellular carcinoma in obese individuals
PNPLA3 I148M (rs738409) genetic variant is associated with hepatocellular carcinoma in obese individuals
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DOI：
10.1016/j.dld.2012.05.006
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发表时间：
2012-12-01
影响因子：
4.5
通讯作者：
Romeo, Stefano
中科院分区：
文献类型：
--
作者：
Burza, Maria Antonella;Pirazzi, Carlo;Romeo, Stefano
背景：肥胖是癌症的危险因素，包括肝细胞癌。帕丁样磷脂酶结构域3 (PNPLA3) I148M （rs738409）基因变异与慢性酒精滥用或肝病毒感染患者的肝细胞癌（HCC）相关。在本研究中，我们研究了来自瑞典肥胖受试者队列（n=4047）的肥胖者的PNPLA3I148M遗传变异与肝细胞癌之间的关系。方法：我们进行了一项匹配，前瞻性，对照，介入性试验，研究减肥手术（手术组）与常规治疗（对照组）对肥胖的影响。结果：中位随访15年共观察到9例事件（对照组5例，手术组4例）。对照组肥胖人群PNPLA3 148M等位基因携带者肝细胞癌发病率显著增高（log-rank p值=0.001），手术组无显著增高（log-rank p值=0.783）。同样，仅在对照组中观察到发生肝细胞癌的风险增加（每个PNPLA3 148M等位基因，风险比为5.9；95%可信区间为1.5-23.8；p值=0.013）。结论：本研究首次前瞻性报道了PNPLA3I148M基因变异与重度肥胖者肝细胞癌的相关性。(C) 2012年意大利胃肠病学出版社，Elsevier Ltd.出版版权所有。
Background: Obesity is a risk factor for cancer, including hepatocellular carcinoma. Patatin-like phospholipase domain-containing 3 (PNPLA3) I148M (rs738409) genetic variant has been associated with hepatocellular carcinoma (HCC) in individuals with chronic alcohol abuse or hepatic viral infection. In the present study we examined the association between the PNPLA3I148M genetic variant and hepatocellular carcinoma in obese individuals from the Swedish Obese Subjects cohort (n=4047).Methods: We performed a matched, prospective, controlled, interventional trial, investigating the effect of bariatric surgery (surgery group) compared to conventional treatment (control group) for obesity.Results: A total of 9 events were observed in the 15-year median follow up (5 in the control group and 4 in the surgery group). A significantly higher incidence of hepatocellular carcinoma in PNPLA3 148M allele carriers was found in obese individuals in the control group (log-rank P-value=0.001), but not in the surgery group (log-rank P-value=0.783). Consistently, an increased risk (for each PNPLA3 148M allele, hazard ratio: 5.9; 95% confidence interval 1.5-23.8; P-value=0.013) of developing hepatocellular carcinoma was observed only in the control group.Conclusion: The current study is the first prospective report showing the association of the PNPLA3I148M genetic variant and hepatocellular carcinoma in severely obese individuals. (C) 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.