Genetic variants of interleukin-1RN and interleukin-1beta genes and risk of cervical cancer

Abstract

Objectives: Inflammation plays a major role in pathogenesis of cervical cancer. We planned to study whether polymorphisms in inflammation-related genes, IL-1RN (VNTR) and IL-1beta (-511C/T), are associated with risk of cervical cancer.

Design: Case-control study.

Setting: Uttar Pradesh state in India.

Sample: One hundred and fifty, histopathologically confirmed cases with cervical cancer and 162 age-, ethnicity-matched, cervical cytology negative, healthy controls were recruited to this study.

Methods: Genotyping of IL-1RN (VNTR) and IL-1beta (-511C/T) polymorphisms was performed using polymerase chain reaction (PCR)/PCR-restriction fragment length polymorphism. Power of study was 80% with type 1 error of 0.05. Haplotypes frequencies were obtained by computer package 'Arlequin'.

Main outcome measures: Haplotype IL-1RN*2/IL-1beta*T is associated with higher risk and of cervical cancer.

Results: IL-1RN genotypes 1/2 and 2/2 were associated with significantly elevated risk of cervical cancer (OR = 3.3; P= 4.9 x 10(-6) and OR = 2.9, P= 0.02). Similarly, TT genotype of IL-1betapolymorphism was significantly higher in cases compared with controls (57.7 versus 38.3%; OR = 2.8; P = 0.012). 2/2 genotype of IL-1RN (OR = 4.8, P = 0.0006) and TT genotype of IL-1beta(OR = 5.2; P = 0.02) were associated with the higher stages (III) of cervical cancer. Haplotypes 1T (IL-1RN*1/IL-1beta*T) and 2T (IL-1RN*2/IL-1beta*T) were also significantly associated with higher susceptibility to cervical cancer and its progression. Logistic regression analysis suggests IL-1RN allele 2 and IL-1beta-511T were independently associated with increased risk for cervical cancer.

Conclusion: IL-1RN*2 and IL-1beta -511*T in various combinations of genotypes and haplotypes are associated with higher susceptibility for cervical cancer.