title: Decreased expression of DNA repair genes (XRCC1, ERCC1, ERCC2, and ERCC4) in squamous intraepithelial lesion and invasive squamous cell carcinoma of the cervix.
abstract: Reduced DNA repair might affect the risk of progression from infection with carcinogenic human papillomavirus (HPV), the etiologic agent for cervical cancer (CC), to persistent HPV infection, and hence to cervical pre-cancer and cancer. We assessed the variation in baseline expression of base excision repair gene XRCC1 and three nucleotide excision repair genes ERCC1, ERCC2, and ERCC4 and the risk of developing cervical cancer. A hospital-based case-control study was designed with 50 invasive cervical cancer patients, 40 squamous intraepithelial lesions (SIL) patients and 85 controls subjects. RT-qPCR and Western blotting was used to quantitate in vitro the mRNA and protein levels in fresh CC, SIL and normal cervix tissue. The levels of XRCC1, ERCC2, ERCC4, and ERCC1 transcripts and their respective proteins were lower in cervical cancer and SILs as compared to controls (p ≤ 0.001, 0.001, 0.001, and 0.025, respectively). In multivariate logistic regression analysis (adjusting for parity, age at first child birth, use of oral contraceptives, smoking status), low expression of XRCC1, ERCC2, ERCC4, and ERCC1 was associated with a significant increased risk for CC and SIL. Our results suggest that individuals whose expression of XRCC1, ERCC4, ERCC2, and ERCC1 are reduced may be at a higher risk of developing SIL which eventually leads to invasive cervical carcinoma. Moreover, independently also the reduced expression of these genes can directly lead to cervical cancer progression.
authors: Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.
authors: Deepti
authors: D
authors: Bajpai
authors: Ayan
authors: A
authors: Banerjee
authors: Sujata
authors: S
authors: Pathak
authors: Sunesh K
authors: SK
authors: Jain
authors: Neeta
authors: N
authors: Singh
mesh_terms: D000328:Adult; D000368:Aged; D002278:Carcinoma in Situ / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004720:Endonucleases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D016017:Odds Ratio; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000076105:X-ray Repair Cross Complementing Protein 1; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; C095888:xeroderma pigmentosum group F protein; C071447:ERCC1 protein, human; D004720:Endonucleases; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human