Genetic variation in the PNPLA3 gene and hepatocellular carcinoma in USA: risk and prognosis prediction.
Genetic variation in the PNPLA3 gene and hepatocellular carcinoma in USA: risk and prognosis prediction.
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DOI：
10.1002/mc.22057
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发表时间：
2013-11
影响因子：
4.6
通讯作者：
Li, Donghui
中科院分区：
文献类型：
--
作者：
Hassan, Manal M.;Kaseb, Ahmed;Etzel, Carol J.;El-Serag, Hashem;Spitz, Margaret R.;Chang, Ping;Hale, Katherine S.;Liu, Mei;Rashid, Asif;Shama, Mohamed;Abbruzzese, James L.;Loyer, Evelyne M.;Kaur, Harmeet;Hassabo, Hesham M.;Vauthey, Jean-Nicolas;Wray, Curtis J.;Hassan, Basmah S.;Patt, Yehuda Z.;Hawk, Ernest;Soliman, Khalid M.;Li, Donghui
非酒精性脂肪性肝病（NAFLD）是一种新出现的流行病，在西方国家患病率很高。全基因组关联研究报道，patatin 样磷脂酶结构域 3 (PNPLA3) 基因的变异与 NAFLD 的高易感性相关。然而，这种变异与肝细胞癌（HCC）之间的关系尚未明确。我们通过开展一项病例对照研究，调查了 PNPLA3 遗传变异（rs738409：C>G）对美国 HCC 风险和预后的影响，该研究包括 257 名新诊断且经病理证实的白人 HCC 患者（病例）和 494 名健康对照。使用多变量逻辑和 Cox 回归模型来控制 HCC 风险和预后因素的混杂影响。我们观察到纯合 GG 基因型受试者比 CC 或 CG 基因型受试者患 HCC 的风险更高，调整后的比值比 (OR) 为 3.21（95% 置信区间 [CI]，1.68-6.41）。我们观察到糖尿病患者的风险改变（OR = 19.11；95% CI，5.13-71.20）。 PNPLA3 GG 基因型与 HCC 患者的潜在肝硬化显着相关（OR = 2.48；95% CI，1.05-5.87）。此外，GG等位基因代表死亡的独立危险因素。与 CC 和 CG 基因型相比，GG 基因型的调整后风险比为 2.11（95% CI，1.26-3.52）。 PNPLA3 遗传变异（rs738409：C>G）可能决定个体对 HCC 发展的易感性和不良预后。为了彻底评估 PNPLA3 的肝癌作用，需要进一步的实验研究。
Nonalcoholic fatty liver disease (NAFLD) is an emerging epidemic with high prevalence in Western countries. Genome-wide association studies had reported that a variation in the patatin-like phospholipase domain containing 3 (PNPLA3) gene is associated with high susceptibility to NAFLD. However, the relationship between this variation and hepatocellular carcinoma (HCC) has not been well established. We investigated the impact of PNPLA3 genetic variation (rs738409: C>G) on HCC risk and prognosis in the United States by conducting a case–control study that included 257 newly diagnosed and pathologically confirmed Caucasian patients with HCC (cases) and 494 healthy controls. Multivariate logistics and Cox regression models were used to control for the confounding effects of HCC risk and prognostic factors. We observed higher risk of HCC for subjects with a homozygous GG genotype than for those with CC or CG genotypes, the adjusted odds ratio (OR) was 3.21 (95% confidence interval [CI], 1.68–6.41). We observed risk modification among individuals with diabetes mellitus (OR = 19.11; 95% CI, 5.13–71.20). The PNPLA3 GG genotype was significantly associated with underlying cirrhosis in HCC patients (OR = 2.48; 95% CI, 1.05–5.87). Moreover, GG allele represents an independent risk factor for death. The adjusted hazard ratio of the GG genotype was 2.11 (95% CI, 1.26–3.52) compared with CC and CG genotypes. PNPLA3 genetic variation (rs738409: C>G) may determine individual susceptibility to HCC development and poor prognosis. Further experimental investigations are necessary for thorough assessment of the hepatocarcinogenic role of PNPLA3.
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影响因子：
13.5
作者：
Browning, JD;Szczepaniak, LS;Hobbs, HH
通讯作者：
Hobbs, HH
影响因子：
6.5
作者：
Lake, AC;Sun, Y;Gimeno, RE
通讯作者：
Gimeno, RE
影响因子：
24.5
作者：
Bellentani, S;Saccoccio, G;Sassatelli, R
通讯作者：
Sassatelli, R
影响因子：
25.7
作者：
El-Serag, HB;Siegel, AB;McGlynn, KA
通讯作者：
McGlynn, KA
影响因子：
45.3
作者：
Patt, YZ;Hassan, MM;Ellis, LM
通讯作者：
Ellis, LM