Dubey Bhawna, Jackson Maria D, Zeigler-Johnson Charnita, Devarajan Karthik, Flores-Obando Rafael E, McFarlane-Anderson Norma, Tulloch-Reid Marshall K, Aiken William, Kimbro Kevin, Jones Dominique Z, Kidd LaCreis R, Ragin Camille
Cancer Prevention and Control Program, Fox Chase Cancer Center, PA, USA.
Department of Community Health and Psychiatry, University of West Indies, Mona, Jamaica.
Gene. 2017 Dec 15;636:96-102. doi: 10.1016/j.gene.2017.09.016. Epub 2017 Sep 10.
African ancestry and obesity are associated with higher risk of prostate cancer (PC). In a pilot study, we explored interactions between obesity (as measured by waist to hip ratio (WHR)) and inflammatory SNPs in relation to PC risk among Jamaican men. This study evaluated 87 chemokine and cytokine associated SNPs in obese and normal weight cases (N=109) and controls (N=102) using a stepwise penalized logistic regression approach in multivariable analyses. Upon stratification by WHR (normal weight (WHR<0.90) or obese (WHR≥0.90)), inheritance of CCR6 rs2023305 AG+GG (OR=1.75, p=0.007), CCR9 rs7613548 AG+GG (OR=1.71, p=0.012) and IL10ra rs2229113 AG+GG (OR=1.45, p=0.01) genotypes was associated with increase in overall or low grade (Gleason score<7) PC risk among normal weight men. These odds were elevated among obese men who possessed the CCR5 rs1799987 AG+GG (OR=1.95, p=0.003) and RNASEL rs12135247 CT+TT genotypes (OR=1.59, p=0.05). CCR7 rs3136685 AG+GG (p=0.032) was associated with a 1.52-1.70 fold increase in the risk of high grade cancer (Gleason score≥7) among obese men. CCR7 variant emerged as an important factor associated with high grade PC risk among obese men in our analyses. Overall, genetic loci found significant in normal weight men were not significant in obese men and vice-versa, partially explaining the role of obesity on PC risk among black men. Also, older age was an important risk factor both in normal weight and obese men but only with regard to low grade PC. Associations of inflammatory SNPs with obesity are suggestive and require further validation in larger cohorts to help develop an understanding of PC risk among obese and non-obese men of African descent.
非洲血统和肥胖与前列腺癌(PC)的较高风险相关。在一项试点研究中,我们探讨了肥胖(以腰臀比(WHR)衡量)与炎症性单核苷酸多态性(SNP)之间的相互作用与牙买加男性患PC风险的关系。本研究在多变量分析中使用逐步惩罚逻辑回归方法,评估了肥胖和正常体重的病例(N = 109)及对照(N = 102)中87个趋化因子和细胞因子相关的SNP。按WHR分层(正常体重(WHR < 0.90)或肥胖(WHR≥0.90))后,正常体重男性中CCR6 rs2023305 AG + GG(OR = 1.75,p = 0.007)、CCR9 rs7613548 AG + GG(OR = 1.71,p = 0.012)和IL10ra rs2229113 AG + GG(OR = 1.45,p = 0.01)基因型的遗传与总体或低级别(Gleason评分<7)PC风险增加相关。在拥有CCR5 rs1799987 AG + GG(OR = 1.95,p = 0.003)和RNASEL rs12135247 CT + TT基因型的肥胖男性中,这些比值升高(OR = 1.59,p = 0.05)。CCR7 rs3136685 AG + GG(p = 0.032)与肥胖男性中高级别癌症(Gleason评分≥7)风险增加1.52 - 1.70倍相关。在我们的分析中,CCR7变异是肥胖男性中与高级别PC风险相关的一个重要因素。总体而言,在正常体重男性中发现有显著意义的基因座在肥胖男性中并不显著,反之亦然,这部分解释了肥胖对黑人男性PC风险的影响。此外,年龄较大在正常体重和肥胖男性中都是一个重要的风险因素,但仅与低级别PC有关。炎症性SNP与肥胖之间的关联具有提示性,需要在更大的队列中进一步验证,以帮助了解非洲裔肥胖和非肥胖男性的PC风险。