Genetic variants of interleukin‐1RN and interleukin‐1β 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-1b (-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-1b (-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-1b*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 · 10 -6 and OR = 2.9, P = 0.02). Similarly, TT genotype of IL-1b polymorphism 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-1b (OR = 5.2; P = 0.02) were associated with the higher stages (III) of cervical cancer. Haplotypes 1T (IL-1RN*1/IL-1b*T) and 2T (IL-1RN*2/IL-1b*T) were also significantly associated with higher susceptibility to cervical cancer and its progression. Logistic regression analysis suggests IL-1RN allele 2 and IL-1b -511T were independently associated with increased risk for cervical cancer.Conclusion IL-1RN*2 and IL-1b -511*T in various combinations of genotypes and haplotypes are associated with higher susceptibility for cervical cancer.

Association of Signal Transducer and Activator of Transcription 3 Gene Polymorphisms with Cervical Cancer in Chinese Women

“…Therefore, genetic variation of immune system factors may influence susceptibility to cervical cancer (Zur Hausen, 2000;Konac et al, 2007;Jumnainsong, et al, 2007;Schlee et al, 2007;Han et al, 2008;Yu et al, 2009). Recent research has investigated SNPs in CD83, IL-1, IL-6, IL-12, VEGF, and nuclear factor-kappa B in cervical cancer patients (Konac et al, 2007;Zhang et al, 2007;Singh et al, 2008;Castro et al, 2009;Chen et al, 2009;Zhou et al, 2010); however, it remains to be elucidated how the genetic variation is involved in the regulation of the immune response and tumorigenesis (Zhang et al, 2007;Yu et al, 2009).…”

“…Yu et al (2009) replicated this study and confirmed the possible role of CD83 polymorphisms in cervical carcinogenesis. Further, polymorphisms in interleukin (IL)-1, IL-6, IL-12, vascular endothelial growth factor (VEGF), and nuclear factor-kappa B have been associated with the risk of cervical carcinoma (Konac et al, 2007;Singh et al, 2008;Castro et al, 2009;Chen et al, 2009;Zhou et al, 2010). Collectively, these findings strongly suggest that polymorphisms in genes may influence susceptibility to cervical cancer.…”

A meta-analysis of the association between CTLA-4 +49 A/G, −318 C/T, and IL-1 polymorphisms and susceptibility to cervical cancer

“…However, previous studies considering the relations between the CTLA-4 and IL-1 polymorphisms and cervical cancer have produced inconsistent results [12][13][14][15][16][17][18][19][20][21][22][23][24][25]. These inconsistencies may be due to the sample sizes, racial/ethnic differences in allele frequencies, or publication bias [26].…”

“…Two were excluded because one was about a different disease [32] and one was about a different polymorphism [33]; thus, 15 studies in total met our inclusion criteria. These consisted of 8 studies on the CTLA-4 polymorphism [12][13][14][15][16][17][18] and 7 on the IL-1 polymorphism [19][20][21][22][23][24][25] (Fig. 1).…”

The role of genetic variation across IL-1β, IL-2, IL-6, and BDNF in antipsychotic-induced weight gain

“…IL-1 is a critically important inflammatory cytokine that is the proposed 'gatekeeper' of inflammation, having numerous and diverse roles in regulating injury and infection 471 . Genetic variation at the rs16944 (G/A) locus has been implicated in several diseases that have an inflammatory component including, but not limited to, gastric cancer 472 , type II diabetes mellitus 473 , osteoarthritis 474 , cervical cancer 475 , and gastroesphageal reflux disease 476 . Genetic association studies have also provided evidence on the involvement of rs16944 in schizophrenia, with reports that implicate the A-allele in illness endophenotypes like elevated brain activation and brain volume reductions 276,277 , and the G-allele in overall disease risk 477,478 .…”