title: Reduced expression of DNA repair genes (XRCC1, XPD, and OGG1) in squamous cell carcinoma of head and neck in North India.
abstract: Squamous cell carcinoma of head and neck (SCCHN) is the sixth most common cancer globally, and in India, it accounts for 30% of all cancer cases. Epidemiological studies have shown a positive association between defective DNA repair capacity and SCCHN. The underlying mechanism of their involvement is not well understood. In the present study, we have analyzed the relationship between SCCHN and the expression of DNA repair genes namely X-ray repair cross-complementing group 1 (XRCC1), xeroderma pigmentosum group D (XPD), and 8-oxoguanine DNA glycosylase (OGG1) in 75 SCCHN cases and equal number of matched healthy controls. Additionally, levels of DNA adduct [8-hydroxyguanine (8-OHdG)] in 45 SCCHN cases and 45 healthy controls were also determined, to ascertain a link between mRNA expression of these three genes and DNA adducts. The relative expression of XRCC1, XPD, and OGG1 in head and neck cancer patients was found to be significantly low as compared to controls. The percent difference of mean relative expression between cases and controls demonstrated maximum lowering in OGG1 (47.3%) > XPD (30.7%) > XRCC1 (25.2%). A negative Spearmen correlation between XRCC1 vs. 8-OHdG in cases was observed. In multivariate logistic regression analysis (adjusting for age, gender, smoking status, and alcohol use), low expression of XRCC1, XPD, and OGG1 was associated with a statistically significant increased risk of SCCHN [crude odds ratios (ORs) (95%CI) OR 2.10; (1.06-4.17), OR 2.76; (1.39-5.49), and 5.24 (2.38-11.52), respectively]. In conclusion, our study demonstrated that reduced expression of XRCC1, XPD, and OGG1 is associated with more than twofold increased risk in SCCHN.
authors.affiliation: CSIR-Indian Institute of Toxicology Research, CSIR-IITR, PO Box 80, MG Marg, Lucknow 226001, India.
authors.forename: Anil
authors.initials: A
authors.lastname: Kumar
authors.forename: Mohan Chand
authors.initials: MC
authors.lastname: Pant
authors.forename: Hirdya Shanker
authors.initials: HS
authors.lastname: Singh
authors.forename: Shashi
authors.initials: S
authors.lastname: Khandelwal
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D045647:DNA Glycosylases / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000076105:X-ray Repair Cross Complementing Protein 1; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human
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