Evaluation of Toll-like receptors 3 (c.1377C/T) and 9 (G2848A) gene polymorphisms in cervical cancer susceptibility

Abstract

Cervical cancer is emerging as a leading cause of morbidity and mortality in women worldwide. Toll-like Receptor (TLR) gene polymorphisms may contribute to subsequent inter-individual variability in cancer susceptibility. The present study aimed to identify the role of TLR 3 (c.1377C/T) [rs3775290] and TLR 9 (G2848A) [rs352140] gene polymorphisms in the risk of developing cervical cancer in North India. Peripheral blood samples were collected from 200 histopathologically confirmed cervical cancer patients from North India and 200 unrelated, cancer-free, age-matched healthy female controls of similar ethnicity. Genomic DNA was extracted using the salting-out method, and genotyped for TLR 3 and TLR 9 using polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). Our data demonstrated a lack of association between TLR 3 (c.1377C/T) and TLR 9 (G2848A) gene polymorphisms and the risk of developing cervical cancer. TLR 3 CT + TT was marginally associated (P = 0.061; age-adjusted OR = 1.46; 95% CI = 0.98-2.16) with cervical cancer susceptibility. The AA genotype of TLR 9 showed borderline significance (P = 0.053) conferring a marginal increased risk (OR = 2.63, 95%CI = 0.99-7.01) for advanced cancer stages (III + IV). Further, TLR 3 and 9 polymorphisms did not have a significant role in modulation of risk due to tobacco usage in cervical cancer patients. Our study suggests only marginal role of TLR 3 and 9 gene polymorphisms in cervical cancer susceptibility in North India; however, future studies in ethnically diverse populations may provide a more comprehensive involvement of innate immunity in cervical cancer etiology in women worldwide.

Associations Between TLR9 Polymorphisms and Cancer Risk: Evidence from an Updated Meta-analysis of 25,685 Subjects

“…The study populations in the 19 included articles consisted of 9 Asian and 10 Caucasian studies. The distribution of genotypes in the controls of all included studies was consistent with Hard-Weinberg equilibrium except for the studies conducted by Mandal et al (2012), Pandey et al (2011), and Lai et al (2013). Detailed characteristics of the included studies are summarized in Table 1.…”

“…However, to date, no studies have demonstrated significant associations between this SNP and breast (Etokebe et al, 2009;Resler et al, 2013), bladder (Singh et al, 2013), prostate (Mandal et al, 2012), colorectal (Li et al, 2009), and cervical cancers (Pandey et al, 2011;Lai et al, 2013), except for one study, which reported an increased risk for cervical cancer (Roszak et al, 2012). Consistent with most of these individual studies, in this meta-analysis incorporating 11 case-control studies with 3775 cases and 3769 controls, we found no significant evidence supporting an association between cancer risk and the rs352140 polymorphism.…”

“…We reviewed the titles, abstracts, and full texts of all retrieved articles through defined criteria. Finally, 19 articles were included in this study (Nieters et al, 2006;Etokebe et al, 2009;Hold et al, 2009;Mollaki et al, 2009;Ashton et al, 2010;Pandey et al, 2011;Zeng et al, 2011;Chen et al, 2012;Carvalho et al, 2012;Li et al, 2012;Mandal et al, 2012;Miedema et al, 2012;Noack et al, 2012;Roszak et al, 2012;Xie et al, 2012;Lai et al, 2013;Resler et al, 2013;Singh et al, 2013;. Since more than one case-control study was included in ten articles (Nieters et al, 2006;Hold et al, 2009;Mollaki et al, 2009;Ashton et al, 2010;Carvalho et al, 2012;Li et al, 2012;Miedema et al, 2012;Roszak et al, 2012;Lai et al, 2013;Resler et al, 2013), they were considered as separate studies in the meta-analysis.…”

“…Moreover, it has been established that TLR9 mediates its functional effects via the myeloid differentiation primary response protein 88 (MyD88)-dependent pathway, leading to nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation, cytokine secretion, and inflammatory responses (Pandey et al, 2011).…”

Homogeneity in Case/Control Numbers and North Indian Caste Criteria in Cervical Cancer/Female Urology Genetic-Studies at a Premier Medical Research Institute in Lucknow, India

“…Cervical cancer data from the most relevant published articles and the doctoral dissertation original research conducted by the author at a premier medical research Institute (Sanjay Gandhi Post Graduate Institute of Medical Sciences) in Lucknow, India demonstrated that sample size numbers were 150 cases/150 controls , 200 cases/200 controls (Pandey et al, 2010), 200 cases/200 controls (Pandey et al, 2011), thereby highlighting homogeneity in the sample cohort data set(s). The total number of clinical samples, including patients and normal healthy study subjects were ≤400 in most of the studies, thus demonstrating the adequacy in sample size and the quality time invested in initial questionnaire-based face to face patient interviews and subsequent clinical specimen collection in collaboration with and/or supervision of the clinical experts/radiation oncologists.…”