Abstract
BackgroundNon-synonymous single nucleotide polymorphisms (SNPs) within vital DNA repair genes may cause reduction of activity leaving the genome unrepaired resulting in genomic instability and cancer.Materials and methodsThe present endeavour involved study on the association of the SNP rs13181 (Lys751Gln/A18911C) in the Nucleotide Excision Repair (NER) pathway gene ERCC2 (excision repair cross-complementing rodent repair deficiency, complementation group 2) with the risks of Squamous Cell Carcinomas of the Head and Neck (SCCHN) and Breast cancer using a case-control based association study among 685 (400 controls and 285 SCCHN-affected cases) and 395 (227 normal healthy female controls and 168 breast cancer cases) ethnically-matched samples, respectively from north India using Polymerase Chain Reaction followed by Restriction Fragment Length Polymorphism (PCR-RFLP) analysis.ResultsResults showed significant association of rs13181 homozygous mutant (CC) [Odds Ratio (OR) 4.412, 95% Confidence Interval (CI) 2.413 to 8.068], heterozygous (AC) (OR 2.086, 95% CI 1.246 to 3.492) and combined mutant (AC + CC) (OR 2.672, 95% CI 1.647 to 4.334) genotypes with predisposition to Breast cancer. Statistically significant increase in SCCHN risk was also associated with the mutant genotypes of rs13181 (ERCC2), viz. homozygous mutant (CC) (OR 1.680, 95% CI 1.014 to 2.784), heterozygous (AC) (OR 1.531, 95% CI 1.092 to 2.149) and combined mutant (AC + CC) (OR 1.560, 95% CI 1.128 to 2.158) genotypes.ConclusionThe results of this case-control study indicate that the polymorphism rs13181 might be a risk factor for predisposition towards SCCHN and breast cancer among north Indian subpopulations.
Highlights
Non-synonymous single nucleotide polymorphisms (SNPs) within vital DNA repair genes may cause reduction of activity leaving the genome unrepaired resulting in genomic instability and cancer
Subsequent analysis concerned assessment of risks associated with individual mutant genotypes, WM, MM and WM + MM with the risk of breast cancer based on Odds ratio (OR), 95% Confidence Intervals (CI) and corresponding P values
The ERCC2 polymorphism, rs13181 located in exon 23, which consists of an A to C substitution in the coding region results in a Lys751Gln substitution in the important domain of interaction between XPD protein and its helicase activator, inside the TFIIH complex [55] which is indicative of a possible involvement of this SNP in defective activity of the gene
Summary
Non-synonymous single nucleotide polymorphisms (SNPs) within vital DNA repair genes may cause reduction of activity leaving the genome unrepaired resulting in genomic instability and cancer. Cancer is a genetic disease resulting from gradual accumulation of changes in the DNA that activate proto-oncogenes and inactivate tumour-suppressor genes leading to genetic instability which is further aggravated by DNA damage and errors made by the DNA maintenance and repair machinery [1]. The ability to metabolize carcinogens or pro-carcinogens, repair DNA damage and control cell signalling and the cell cycle are important examples of low- and medium-penetrance genes fundamental to homoeostasis which is why most cancers, including Squamous Cell Carcinomas of the Head and Neck (SCCHN) and Breast Cancer are based on these main factors [8,9]. Well-established risk factors ascribed to breast cancer include early menarche, late menopause, age of first child's birth, nulliparity and family history (FH) [11]
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