An Epidemiologic and Genomic Investigation Into the Obesity Paradox in Renal Cell Carcinoma
An Epidemiologic and Genomic Investigation Into the Obesity Paradox in Renal Cell Carcinoma
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DOI：
10.1093/jnci/djt310
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发表时间：
2013-12-01
影响因子：
10.3
通讯作者：
Russo, Paul
中科院分区：
文献类型：
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作者：
Hakimi, A. Ari;Furberg, Helena;Russo, Paul
肥胖会增加肾透明细胞癌（ccRCC）的风险，但肥胖患者的生存期似乎比非肥胖患者更长。我们检查了体重指数（BMI）与分期、分级和癌症特异性死亡率（CSM）的关系，同时考虑了检测偏倚、营养状况和肿瘤分子特征。数据来自1995年至2012年在纪念斯隆-凯特琳癌症中心接受肾脏肿块手术的2119例ccRCC患者。Logistic回归模型显示BMI与晚期疾病之间存在相关性。多变量竞争风险回归模型估计BMI和CSM之间的关联。使用KruskalWallis或Fisher精确检验，在参与ccRCC癌症基因组图谱项目的126名患者的子集中，通过BMI检查体细胞突变、拷贝数、甲基化和表达数据。所有统计检验均为双侧检验，与正常体重患者相比，肥胖和超重患者出现晚期疾病的可能性较小（比值比[OR] 0.61，95%置信区间[CI] 0.48 - 0.79 vs OR 0.65，95% CI 0.51 - 0.83）。在单变量分析中，较高的BMI与CSM降低相关（P <0.005）。在校正合并症和白蛋白水平后仍有统计学意义，但在校正分期和分级后无统计学意义（P > 0.10）。BMI的全基因组询问表明代谢和脂肪酸基因（包括脂肪酸合成酶（FATCH））的基因表达存在差异，这与肥胖悖论一致。我们的研究结果表明，尽管BMI不是CSM的独立预后因素，但在控制了分期和分级后，在致肥胖环境中发展的肿瘤可能更惰性。
Obesity increases risk for clear-cell renal cell carcinoma (ccRCC), yet obese patients appear to experience longer survival than nonobese patients. We examined body mass index (BMI) in relation to stage, grade, and cancer-specific mortality (CSM) while considering detection bias, nutritional status, and molecular tumor features.Data were available from 2119 ccRCC patients who underwent renal mass surgery at Memorial Sloan-Kettering Cancer Center between 1995 and 2012. Logistic regression models produced associations between BMI and advanced disease. Multivariable competing risks regression models estimated associations between BMI and CSM. Somatic mutation, copy number, methylation, and expression data were examined by BMI among a subset of 126 patients who participated in the Cancer Genome Atlas Project for ccRCC using the KruskalWallis or Fisher exact tests. All statistical tests were two-sided.Obese and overweight patients were less likely to present with advanced-stage disease compared with normal-weight patients (odds ratio [OR] 0.61, 95% confidence interval [CI] 0.48 to 0.79 vs OR 0.65, 95% CI 0.51 to 0.83, respectively). Higher BMI was associated with reduced CSM in univariable analyses (P < .005). It remained statistically significant after adjustment for comorbidities and albumin level, but it became non-statistically significant after adjusting for stage and grade (P > .10). Genome-wide interrogation by BMI suggested differences in gene expression of metabolic and fatty acid genes, including fatty acid synthase (FASN), consistent with the obesity paradox.Our findings suggest that although BMI is not an independent prognostic factor for CSM after controlling for stage and grade, tumors developing in an obesogenic environment may be more indolent.