IL-1 gene polymorphisms and genetic susceptibility of gallbladder cancer in a north Indian population

Long-standing gallstones are generally present in 65-80% patients of gallbladder cancer (GBC). It has also been sugested that inflammation caused by gallstones may be involved in the development of GBC. Interleukin-I receptor antagonist (IL-IRN) and interleukin-I beta (IL-IB) are proinflammatory cytokine genes at the interleukin-I locus, and polymorphisms of these genes have been associated with various inflammatory diseases. The aim of this study was to investigate whether polymorphism in the IL-IRN and IL-IB genes arc associatcd with GBC patients with and without gallstones. Polymorphisms within the IL-IRN 86-base pair VNTR (variable number tandem repeat) and IL-IB (-511C -> T) were genotyped using polymerase chain reaction (PCR) and PCR restriction fragment length polymorphism in 166 healthy subjects and 124 GBC patients. The frequency of the IL-IRN, VNTR 2/2 genotype was significantly higher in GBC patients [P = 0.017; odds ratio (OR) = 3.25; 95% confidence interval (CI) = 1.23-8.58]. CC genotype and 'C' allele of the -511IL-IB C -> T polymorphism also showed high risk for GBC (P = 0.033; OR = 3.36; 95%CI = 1.52-7.43, P = 0.047, OR = 1.41; 95%CI = 1.00-1.98, respectively). The higher cancer risk due to the IL-IRN. 2/2 genotype was observed in GBC patients with or without stories (P = 0.038; OR = 3.58; 95%CI = 1.08-11.65, P = 0.035 OR = 3.33; 95%CI 1.08-10.61). Risk due to the CC genotype of IL-IB, however, was confined to GBC patients harboring gallstones (P = 0.0003; OR = 6.92; 95%CI = 2.65-18.03). The haplotype I/C of IL-IRN and IL-IB was found to confer a significantly enhanced risk of GBC in cancer patients with gallstones (P = 0.022; OR = 2.19; 95%CI = 1.12-4.27), while higher risk resulting from 2/C haplotype was of borderline significance (P = 0.061; OR = 3.04; 95%CI = 0.95-9.70). Individuals with 1/C and 2/C haplotypes of IL-IRN VNTR and -511IL-IB C -> T Polymorphisms were more susceptible to develop GBC with gallstones compared to healthy controls in north India. (C) 2008 Elsevier Inc. All rights reserved.