PNPLA3 I148M polymorphism, clinical presentation, and survival in patients with hepatocellular carcinoma.
PNPLA3 I148M polymorphism, clinical presentation, and survival in patients with hepatocellular carcinoma.
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DOI：
10.1371/journal.pone.0075982
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Fracanzani AL
中科院分区：
文献类型：
--
作者：
Valenti L;Motta BM;Soardo G;Iavarone M;Donati B;Sangiovanni A;Carnelutti A;Dongiovanni P;Rametta R;Bertelli C;Facchetti F;Colombo M;Fargion S;Fracanzani AL
本研究的目的是评估先前与肝细胞癌 (HCC) 风险相关的 PNPLA3 I148M 多态性是否影响 HCC 的临床表现和生存。我们考虑了 460 名连续转诊至意大利北部三级护理中心的 HCC 患者，其中 353 名患者有随访数据。 PNPLA3 148M 危险等位基因的纯合性在患有酒精性肝病或非酒精性脂肪性肝病的 HCC 患者中较多（ALD 和 NAFLD：相对风险 5.9，95% c.i. 3.5–9.9；其他肝脏疾病：相对风险 1.9，95% c.i. 1.1–3.4）。在 ALD 和 NAFLD 患者中，PNPLA3 148M 等位基因与年龄较小、肝硬化病史较短、HCC 诊断时进展程度较低（儿童 A）肝硬化以及较低的 HCC 分化级别相关（p<0.05）。 PNPLA3 148M 纯合性与整个系列中的生存率降低相关 (p = 0.009)，并且与就诊时 HCC 病变数量较多 (p = 0.007) 以及 ALD 和 NAFLD 患者的生存率降低相关 (p = 0.003；中位生存期为 30、95% c.i. 20-39 vs. 95% c.i. 20-39。 45, 95% c.i. 38-52 个月），但在与其他病因相关的 HCC 患者中则不然（p = 0.86；48, 95% c.i. 32-64 对比 55, 95% c.i. 43-67 个月）。在多变量 Cox 回归分析中，PNPLA3 148M 纯合性是 ALD 和 NAFLD 患者生存的唯一阴性预测因子（死亡 HR 1.57，95% c.i. 1.12–2.78）。 PNPLA3 148M 在 ALD 和 NAFLD HCC 患者中的比例过高，并且与 ALD 和 NAFLD 中较晚期肝病的发生相关。在 ALD 和 NAFLD 中，PNPLA3 148M 与就诊时更弥漫的 HCC 相关，并且与生存率降低相关。
Aim of this study was to evaluate whether the PNPLA3 I148M polymorphism, previously associated with hepatocellular carcinoma (HCC) risk, influences the clinical presentation of HCC and survival. we considered 460 consecutive HCC patients referred to tertiary care centers in Northern Italy, 353 with follow-up data. Homozygosity for PNPLA3 148M at risk allele was enriched in HCC patients with alcoholic liver disease or nonalcoholic fatty liver disease (ALD&NAFLD: relative risk 5.9, 95% c.i. 3.5–9.9; other liver diseases: relative risk 1.9, 95% c.i. 1.1–3.4). In ALD&NAFLD patients, the PNPLA3 148M allele was associated with younger age, shorter history of cirrhosis, less advanced (Child A) cirrhosis at HCC diagnosis, and lower HCC differentiation grade (p<0.05). Homozygosity for PNPLA3 148M was associated with reduced survival in the overall series (p = 0.009), and with a higher number of HCC lesions at presentation (p = 0.007) and reduced survival in ALD&NAFLD patients (p = 0.003; median survival 30, 95% c.i. 20–39 vs. 45, 95% c.i. 38–52 months), but not in those with HCC related to other etiologies (p = 0.86; 48, 95% c.i. 32–64 vs. 55, 95% c.i. 43–67 months). At multivariate Cox regression analysis, homozygosity for PNPLA3 148M was the only negative predictor of survival in ALD&NAFLD patients (HR of death 1.57, 95% c.i. 1.12–2.78). PNPLA3 148M is over-represented in ALD&NAFLD HCC patients, and is associated with occurrence at a less advanced stage of liver disease in ALD&NAFLD. In ALD&NAFLD, PNPLA3 148M is associated with more diffuse HCC at presentation, and with reduced survival.
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影响因子：
2.4
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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
通讯作者：
Li, Donghui