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Cervical Carcinogenesis and Immune Response Gene Polymorphisms: A Review.

ABSTRACT: The local immune response is considered a key determinant in cervical carcinogenesis after persistent infection with oncogenic, high-risk human papillomavirus (HPV) infections. Genetic variation in various immune response genes has been shown to influence risk of developing cervical cancer, as well as progression and survival among cervical cancer patients. We reviewed the literature on associations of immunogenetic single nucleotide polymorphism, allele, genotype, and haplotype distributions with risk and progression of cervical cancer. Studies on HLA and KIR gene polymorphisms were excluded due to the abundance on literature on that subject. We show that multiple genes and loci are associated with variation in risk of cervical cancer. Rather than one single gene being responsible for cervical carcinogenesis, we postulate that variations in the different immune response genes lead to subtle differences in the effectiveness of the antiviral and antitumour immune responses, ultimately leading to differences in risk of developing cervical cancer and progressive disease after HPV infection.

SUBMITTER: Mehta AM

PROVIDER: S-EPMC5322437 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Cervical Carcinogenesis and Immune Response Gene Polymorphisms: A Review.

Mehta Akash M AM Mooij Merel M Branković Ivan I Ouburg Sander S Morré Servaas A SA Jordanova Ekaterina S ES

Journal of immunology research 20170209

The local immune response is considered a key determinant in cervical carcinogenesis after persistent infection with oncogenic, high-risk human papillomavirus (HPV) infections. Genetic variation in various immune response genes has been shown to influence risk of developing cervical cancer, as well as progression and survival among cervical cancer patients. We reviewed the literature on associations of immunogenetic single nucleotide polymorphism, allele, genotype, and haplotype distributions wi ...[more]

PMID: 28280748

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Project description:Early childhood caries is a significant public health concern affecting about 600 million children globally. The etiology of early childhood caries can be explained as an interplay between genetic and environmental factors. Single nucleotide polymorphisms are the most common variations in the human genome. Genetic variations of immune response genes can modify the defense response of the host, and alter the susceptibility to bacterial colonization of the oral cavity and early childhood caries. The aim of this systematic review is to identify genetic variants of immune response genes associated with early childhood caries. A total of 7124 articles were identified by conducting an elaborate search across various electronic databases and genome-wide association studies databases. Subsequent to exclusion at various stages, fifteen articles qualified to be included into the present review. Risk of bias assessment was done with the Q-genie tool. Quantitative synthesis revealed that the odds ratio for TT and CC genotypes of rs11362 was 1.07 (0.67-1.71) and 1.16 (0.84-1.60), respectively. Gene-based analysis revealed a statistically significant association between variants of tumor necrosis factor-alpha gene and T-cell receptor alpha variable 4 locus with early childhood caries. Gene clustering showed the presence of three functional clusters. To comprehend the protein-protein interaction, the bioinformatic tool of "Search Tools for the Retrieval of Interacting Genes and Proteins" was used. Among the biological processes and the reactome pathways, complement activation through the lectin pathway showed the highest strength of association with early childhood caries. To understand the interaction and functionality of the genes, "gene function prediction using Multiple Association Network Integration Algorithm" was used, which revealed that the genes were linked by physical interaction (39.34%) and through co-expression (34.88%). Genotype TT of rs7217186 of arachidonate 15-lipoxygenase gene was a risk factor for early childhood caries. Multiple genetic variants of T-cell receptor alpha variable 4 locus and tumor necrosis factor-alpha gene were associated with increased susceptibility to early childhood caries. Polymorphisms of genes regulating the lectin pathway of complement activation can modify the susceptibility to early childhood caries.

Project description:Background & aimsInflammation is a major risk factor for development of colorectal cancer (CRC). Prostaglandin synthase cyclooxygenase-2 (COX-2) encoded by the PTGS2 gene is the rate limiting enzyme in prostaglandin synthesis and therefore plays a distinct role as regulator of inflammation.MethodsPTGS2 mRNA levels were determined in intestinal tissues from 85 intestinal adenoma cases, 115 CRC cases, and 17 healthy controls. The functional PTGS2 polymorphisms A-1195G (rs689466), G-765C (rs20417), T8473C (rs5275) were assessed in 200 CRC cases, 991 adenoma cases and 399 controls from the Norwegian KAM cohort.ResultsPTGS2 mRNA levels were higher in mild/moderate adenoma tissue compared to morphologically normal tissue from the same individual (P<0.0001) and (P<0.035) and compared to mucosa from healthy individuals (P<0.0039) and (P<0.0027), respectively. In CRC patients, PTGS2 mRNA levels were 8-9 times higher both in morphologically normal tissue and in cancer tissue, compared to healthy individuals (P<0.0001). PTGS2 A-1195G variant allele carriers were at reduced risk of CRC (odds ratio (OR) = 0.52, 95% confidence interval (95% CI): 0.28-0.99, P = 0.047). Homozygous carriers of the haplotype encompassing the A-1195G and G-765C wild type alleles and the T8473C variant allele (PTGS2 AGC) were at increased risk of CRC as compared to homozygous carriers of the PTGS2 AGT (A-1195G, G-765C, T8473C) haplotype (OR = 5.37, 95% CI: 1.40-20.5, P = 0.014). No association between the investigated polymorphisms and PTGS2 mRNA levels could be detected.ConclusionHigh intestinal PTGS2 mRNA level is an early event in colorectal cancer development as it occurs already in mild/moderate dysplasia. PTGS2 polymorphisms that have been associated with altered PTGS2 mRNA levels/COX-2 activity in some studies, although not the present study, were associated with colorectal cancer risk. Thus, both PTGS2 polymorphisms and PTGS2 mRNA levels may provide information regarding CRC risk.

Dataset Information

Cervical Carcinogenesis and Immune Response Gene Polymorphisms: A Review.

Publications

Cervical Carcinogenesis and Immune Response Gene Polymorphisms: A Review.

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