title: The protective role of the -1306C>T functional polymorphism in matrix metalloproteinase-2 gene is associated with cervical cancer: implication of human papillomavirus infection.
abstract: Cervical cancer is the major reproductive health problem among women caused by persistent infection of high-risk human papillomavirus (HR-HPV). Metalloproteinase-2 (MMP-2) is an endopeptidase highly expressed in cervical cancer; however, the genetic link between aberrant expression of MMP-2 and cervical carcinogenesis is not known. The genotypic distribution, expression pattern of MMP-2 and HPV infection, was analyzed in a total of 300 fresh surgically resected cervical tissue biopsies. The MMP-2 C1306T (rs243865) promoter polymorphism dominant model (CC v/s CT + CT + TT) revealed that the CC genotype had a 4.33-fold significant increased risk for development of cervical cancer (OR = 4.33; 95 % CI = 2.36-4.02, p = 0.0001) compared to those with variant genotypes (-1306 CT + TT). The C allele was associated with 3-fold significant increased risk (OR = 2.95; 95 % CI = 1.90-4.60, p = 0.0002) compared to T allele. Interestingly, a significant correlation was found between high expression of MMP-2 protein and CC genotype in cancer patients (p = 0.001) compared to normal controls (p = 0.012). Further analysis showed that the risk of cancer was extremely pronounced in HPV positive patients (OR = 9.33; 95 % CI = 2.88-30.20, p = 0.0001) compared to HPV negative ones, implicating the possible interaction between -1306CC genotype and HPV infection in increasing the cancer risk (p = 0.0001). The leads from the present study suggest the protective role of gene variant -1306C>T at the promoter region of the MMP-2 against HPV-mediated cervical cancer. These findings substantiate the functional role of MMP-2 C1306T polymorphism in a significant downregulation of MMP-2 protein in women with variant genotype (CT/TT) compared to the normal wild CC genotype.
authors.affiliation: Systems Biology Research Centre-Tumor biology, School of Life Sciences, University of Skövde, Skövde, SE-54128, Sweden. neha.singh@his.se.|Department of Biotechnology, Panjab University, Chandigarh, India. neha.singh@his.se.
authors.forename: Neha
authors.initials: N
authors.lastname: Singh
authors.affiliation: Division of Molecular Oncology, Institute of Cytology and Preventive Oncology (ICMR), Noida, India. shussain1712@yahoo.co.in.
authors.forename: Showket
authors.initials: S
authors.lastname: Hussain
authors.affiliation: Division of Molecular Genetics and Biochemistry, Institute of Cytology and Preventive Oncology (ICMR), Noida, India.
authors.forename: Upma
authors.initials: U
authors.lastname: Sharma
authors.affiliation: Department of Obstetrics and Gynecology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Vanita
authors.initials: V
authors.lastname: Suri
authors.affiliation: Department of Cytology & Gynae. Pathology, Post Graduate Institute of Medical Education and Research, Sector-12, Chandigarh, India.
authors.forename: Raje
authors.initials: R
authors.lastname: Nijhawan
authors.affiliation: Division of Molecular Genetics and Biochemistry, Institute of Cytology and Preventive Oncology (ICMR), Noida, India.
authors.forename: Mausumi
authors.initials: M
authors.lastname: Bharadwaj
authors.affiliation: Department of Biotechnology, Panjab University, Chandigarh, India. rcsobti@pu.ac.in.|Vice Chancellor BBA (Central) University, Lucknow, India. rcsobti@pu.ac.in.
authors.forename: R C
authors.initials: RC
authors.lastname: Sobti
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D052161:Human papillomavirus 18 / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000235:genetics* / Q000473:pathology / Q000821:virology; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology
chemical_list: D020778:Matrix Metalloproteinase 2
keywords: Cervical cancer; HPV; MMP-2; Promoter polymorphism