Interactions of cytokine gene polymorphisms in prostate cancer risk.
Prostate cancer (CaP) is the second leading cause of cancer death in American men. Chronic inflammation has been one of several factors associated with the development of CaP. Single-nucleotide polymorphisms (SNPs) in cytokine genes have been associated with increased inflammation, increased cytokine production and possibly increased CaP risk. However, the effects of cytokine SNPs on CaP susceptibility have not been consistent. Using the genomic DNA collected in a CaP case-control study (557 cases and 547 controls), we pilot tested the interactions of nine functionally characterized SNPs of three cytokine genes in CaP risk using the multivariate adaptive regression splines (MARS)-logit models. African-Americans with the IL10-819TT genotype had a lower CaP risk [odds ratio (OR) = 0.27, 95% confidence interval (CI) = 0.07-1.01], but subjects with the genotype combination of IL1B-511CT/TT and IL10-592CC had a higher CaP risk (OR = 2.56, 95% CI = 1.09-6.02). In Caucasians, higher CaP risk was associated with the IL10-1082AG/GG genotype (OR = 3.62, 95% CI = 1.42-9.28), the genotype combination of IL10-1082AA plus IL1B-31TT/TC (OR = 2.92, 95% CI = 1.13-7.55) and the genotype combination of TNF-238GG plus IL10-592AA (OR = 2.14, 95% CI = 1.05-4.38). Our results highlight the importance of cytokine SNPs and their interactions in CaP risk.
Zabaleta
Jovanny
J
Department of Genetics, Louisiana State University Health Sciences Center, 533 Bolivar Street, CSRB 455, New Orleans, LA 70112, USA. jzabal@lsuhsc.edu
Lin
Hui-Yi
HY
Sierra
Rosa A
RA
Hall
M Craig
MC
Clark
Peter E
PE
Sartor
Oliver A
OA
Hu
Jennifer J
JJ
Ochoa
Augusto C
AC
D044383:Black People; D016022:Case-Control Studies; D016207:Cytokines / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000208:ethnology / Q000235:genetics*; D012307:Risk Factors; D044465:White People; D001741:Black or African American
D016207:Cytokines