Affiliations of authors: Urology Service, Department of Surgery (AAH, NM, BF, PHK, PR), Human Oncology & Pathogenesis Program (AAH, JJH); Epidemiology and Biostatistics (HF, ECZ), Computational Biology (AJ, NS, GC, CS), Genitourinary Oncology (MHV, RJM, JJH), and Department of Pathology (VER), Memorial Sloan-Kettering Cancer Center, New York, NY; USC Epigenome Center, University of Southern California, Los Angeles, California (HS, PWL); Weill Medical College, Cornell University, New York, NY (RJM, JJH, PR).
J Natl Cancer Inst. 2013 Dec 18;105(24):1862-70. doi: 10.1093/jnci/djt310. Epub 2013 Nov 27.
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 Kruskal-Wallis 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.
肥胖会增加透明细胞肾细胞癌（ccRCC）的风险，但肥胖患者的生存时间似乎比非肥胖患者长。我们研究了体重指数（BMI）与肿瘤分期、分级和癌症特异性死亡率（CSM）之间的关系，同时考虑了检测偏倚、营养状况和肿瘤分子特征。
数据来自于 1995 年至 2012 年期间在纪念斯隆-凯特琳癌症中心接受肾肿瘤手术的 2119 名 ccRCC 患者。逻辑回归模型得出了 BMI 与晚期疾病之间的关联。多变量竞争风险回归模型估计了 BMI 与 CSM 之间的关联。在癌症基因组图谱项目中，对 126 名参与 ccRCC 的患者的亚组进行了 BMI 与体细胞突变、拷贝数、甲基化和表达数据的检查，使用 Kruskal-Wallis 或 Fisher 精确检验。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低（比值比[OR] = 0.61，95%置信区间[CI] = 0.48 至 0.79；OR = 0.65，95% CI = 0.51 至 0.83）。单变量分析显示，较高的 BMI 与 CSM 降低相关（P <.005）。在调整合并症和白蛋白水平后，这一结果仍然具有统计学意义，但在调整肿瘤分期和分级后，这一结果变得不具有统计学意义（P >.10）。按 BMI 进行的全基因组检测提示代谢和脂肪酸基因表达的差异，包括脂肪酸合酶（FASN），这与肥胖悖论一致。
尽管在控制肿瘤分期和分级后，BMI 不是 CSM 的独立预后因素，但在肥胖环境中发展的肿瘤可能更惰性。
