Department of Molecular and Clinical Medicine and Center for Cardiovascular and Metabolic Research, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Dig Liver Dis. 2012 Dec;44(12):1037-41. doi: 10.1016/j.dld.2012.05.006. Epub 2012 Jun 15.
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 PNPLA3 I148M genetic variant and hepatocellular carcinoma in obese individuals from the Swedish Obese Subjects cohort (n = 4047).
We performed a matched, prospective, controlled, interventional trial, investigating the effect of bariatric surgery (surgery group) compared to conventional treatment (control group) for obesity.
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.
The current study is the first prospective report showing the association of the PNPLA3 I148M genetic variant and hepatocellular carcinoma in severely obese individuals.
肥胖是癌症的一个风险因素，包括肝细胞癌。载脂蛋白样磷脂酶结构域包含 3 型（PNPLA3）I148M（rs738409）基因变异与慢性酒精滥用或肝病毒感染个体的肝细胞癌（HCC）相关。在本研究中，我们研究了瑞典肥胖受试者队列（n = 4047）中肥胖个体的 PNPLA3 I148M 基因变异与肝细胞癌之间的关联。
我们进行了一项匹配的前瞻性对照干预试验，研究了减肥手术（手术组）与常规治疗（对照组）对肥胖的影响。
在 15 年的中位随访中，共观察到 9 例事件（对照组 5 例，手术组 4 例）。在对照组肥胖个体中，PNPLA3 148M 等位基因携带者的肝细胞癌发生率显著升高（log-rank P 值= 0.001），但在手术组中未观察到（log-rank P 值= 0.783）。一致地，仅在对照组中观察到 PNPLA3 148M 等位基因每增加一个，肝细胞癌发病风险增加（危险比：5.9；95%置信区间 1.5-23.8；P 值= 0.013）。
本研究是第一项前瞻性报告，显示了 PNPLA3 I148M 基因变异与严重肥胖个体中肝细胞癌的关联。
