Association of TNFA (−308G>A) and IL-10 (−819C>T) Promoter Polymorphisms With Risk of Cervical Cancer

Abstract

Etiology of cervical cancer is associated with excessive inflammation mediated tumorigenesis. Pro and anti-inflammatory cytokines (tumor necrosis factor alpha, TNFA and interleukin, IL-10) are involved in fighting against the tumorigenesis. Therefore, the present study was designed to evaluate the association of TNFA (-308G>A) and IL-10 (-819C>T) gene polymorphism with risk of cervical cancer. One hundred fifty histopathologically confirmed patients with cervical cancer and 162 age, ethnically-matched cervical cytology negative healthy controls were genotyped for TNFA (-308 G>A) and IL-10 (-819 C>T) polymorphisms using PCR-RFLP. Individuals with combination of TNFA -308GA+AA genotype and A allele were at elevated risk of cervical cancer (odds ratio (OR) = 2.24; P = 0.018 and OR, 2.05; P = 0.012). Frequency of IL-10 -819CT+TT genotype combination and T allele was slightly higher in cases as compared with controls but difference was not significant (OR = 1.52; P = 0.069 and OR = 1.38; P = 0.051). In association of genotypes with clinical characteristics, presence of TNFA -308GA+AA genotype conferred high risk for the stages (IB) (OR = 2.86, P = 0.039) and stages (III) (OR = 2.52; P = 0.015) of cervical cancer. In contrast, IL-10 -819TT genotype was not associated with higher risk of clinical characteristics of cervical cancer. In conclusion, individuals with TNFA -308*A allele carriers were at significantly higher risk of cervical cancer particularly early (IB) and advanced stages (III). However, IL-10 (-819C>T) polymorphism was not associated with risk of cervical cancer.

Association of TNF-α-308 and -238 Polymorphisms with Risk of Cervical Cancer: A Meta-analysis

“…The two most commonly studied polymorphisms were G to A substitutions in the promoter region at positions -308 and -238 which have been shown to influence the TNF-α expression (Fong et al, 1994;Kroeger et al, 1997). A large number of studies have been conducted to investigate the associations between these two variants and cervical cancer risk; however, results from these studies were still ambiguous due to small sample size, unified ethnicity, and low statistical power of individual studies (Jang et al, 2001;Calhoun et al, 2002;Gostout et al, 2003;Stanczuk et al, 2003;Deshpande et al, 2005;Duarte et al, 2005;Govan et al, 2006;Kohaar et al, 2007;Ivansson et al, 2008;Singh et al, 2009;Wang et al, 2009;Ivansson et al, 2010;Wang et al, 2011). Meta-analysis is a potent method through pooling of data from individual association studies, thereby increasing the sample size and enhancing the statistical power.…”

“…The results of the HWE test for the genotypes distribution in controls were also listed in Table 2. All studies did not deviate from HWE except for four studies (Govan et al, 2006;Singh et al, 2009;Ivansson et al, 2010;Wang et al, 2011) for the TNF-α-308G>A polymorphism.…”

“…Govan's study (2006) contained data on two independent populations and thus was treated as two separate studies. Finally, a total of 13 separate studies were included in this meta-analysis based on the inclusion criteria (Jang et al, 2001Calhoun et al, 2002Gostout et al, 2003;Stanczuk et al, 2003;Deshpande et al, 2005;Duarte et al, 2005;Govan et al, 2006;Kohaar et al, 2007;Ivansson et al, 2008;Singh et al, 2009;Wang et al, 2009;Ivansson et al, 2010;Wang et al, 2011), which involved 3294 cervical cancer patients and 3468 controls. Of eligible studies, seven studies were conducted in Caucasian population, two studies for Asian, African and mixed-ancestry population, respectively.…”

“…However, the results from previous studies that were conducted to assess the association of these two polymorphisms (-308 G>A and -238 G>A) with cervical cancer are still inconclusive or contradictory (Jang et al, 2001;Calhoun et al, 2002;Gostout et al, 2003;Stanczuk et al, 2003;Deshpande et al, 2005;Duarte et al, 2005;Govan et al, 2006;Kohaar et al, 2007;Ivansson et al, 2008;Singh et al, 2009;Wang et al, 2009;Ivansson et al, 2010;Wang et al, 2011). This inconsistency may be partially attributed to studies with relative small sample size, inadequate statistical power, racial and ethnic differences, publication bias, or uncorrected multiple hypothesis testing.…”

Association of tumor necrosis factor-α 308G/A polymorphism with urogenital cancer risk: a systematic review and meta-analysis

“…There are 13 studies (Oh et al, 2000;McCarron et al, 2002;Wu, 2004;Jinchao, 2007;Danforth et al, 2008;Sáenz-López et al, 2008;Zabaleta et al, 2008;Kesarwani, 2009;Moore et al, 2009;Wang et al, 2009a;Zhang et al, 2010;Berhane et al, 2012;Jones et al, 2013) focusing on prostate cancer, 19 studies (Jang et al, 2001;Calhoun et al, 2002;Gostout et al, 2003;Stanczuk et al, 2003;Deshpande et al, 2005;Duarte et al, 2005;Govan, 2006;Kohaar et al, 2007;Singh, 2009;Wang et al, 2009b;Ivansson, 2010;Zu, 2010;Wang et al, 2011;Zuo et al, 2011;Badano et al, 2012;Barbisan et al, 2012;Hang and Xu, 2012;Wang et al, 2012;Sousa et al, 2014) on cervical cancer, 6 studies (Tsai et al, 2001;Jeong et al, 2004;Kim et al, 2005;Leibovici et al, 2005;Nonomura et al, 2006;Ahirwar et al, 2008) on bladder cancer, 1 study (Jang et al, 2001) on renal cell cancer, and 1 study (Wu, 2013) on urothelial carcinoma. Five articles (Stanczuk et al, 2003;…”