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

Abstract

Long-standing gallstones are generally present in 65–80% patients of gallbladder cancer (GBC). It has also been suggested that inflammation caused by gallstones may be involved in the development of GBC. Interleukin-1 receptor antagonist (IL-1RN ) and interleukin-1 beta (IL-1B ) are proinflammatory cytokine genes at the interleukin-1 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-1RN and IL-1B genes are associated with GBC patients with and without gallstones. Polymorphisms within the IL-1RN 86–base pair VNTR (variable number tandem repeat) and IL-1B (−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-1RN, 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 –511 IL-1B 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-1RN, 2/2 genotype was observed in GBC patients with or without stones ( 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-1B, however, was confined to GBC patients harboring gallstones ( P = 0.0003; OR = 6.92; 95%CI = 2.65–18.03). The haplotype 1/C of IL-1RN and IL-1B 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-1RN VNTR and –511 IL-1B C → T polymorphisms were more susceptible to develop GBC with gallstones compared to healthy controls in north India.