Inflammation polymorphisms and prostate cancer risk in Jamaican men: Role of obesity/body size

被引:5
作者
Dubey, Bhawna [1 ]
Jackson, Maria D. [2 ]
Zeigler-Johnson, Charnita [3 ]
Devarajan, Karthik [4 ]
Flores-Obando, Rafael E. [5 ]
McFarlane-Anderson, Norma [6 ]
Tulloch-Reid, Marshall K. [7 ]
Aiken, William [8 ]
Kimbro, Kevin [9 ]
Jones, Dominique Z. [10 ]
Kidd, LaCreis R. [10 ]
Ragin, Camille [1 ,11 ]
机构
[1] Fox Chase Canc Ctr, Canc Prevent & Control Program, 333 Cottman Ave, Philadelphia, PA 19111 USA
[2] Univ West Indies, Dept Community Hlth & Psychiat, Mona, Jamaica
[3] Thomas Jefferson Univ, Dept Med Oncol, Div Populat Sci, Philadelphia, PA 19107 USA
[4] Fox Chase Canc Ctr, Biostat & Bioinformat, 7701 Burholme Ave, Philadelphia, PA 19111 USA
[5] State Univ New York, Mol & Cellular Biol Program, Brooklyn, NY USA
[6] Univ West Indies, Dept Basic Med Sci, Mona Campus, Kingston, Jamaica
[7] Univ West Indies, Caribbean Inst Hlth Res, Kingston, Jamaica
[8] Univ West Indies, Fac Med Sci, Sect Surg, Dept Surg Radiol Anaesthesia & Intens Care, Kingston 7, Jamaica
[9] North Carolina Cent Univ, BBRI, Durham, NC USA
[10] Univ Louisville, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA
[11] Temple Univ, Coll Publ Hlth, Dept Epidemiol & Biostat, Philadelphia, PA 19122 USA
关键词
Prostate cancer; Obesity; Waist to hip ratio; Black; Single nucleotide polymorphisms; PHYSICAL-ACTIVITY; ADIPOSE-TISSUE; EXPRESSION; INCREASES; RECEPTOR;
D O I
10.1016/j.gene.2017.09.016
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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.
引用
收藏
页码:96 / 102
页数:7
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