title: XRCC2 R188H (rs3218536), XRCC3 T241M (rs861539) and R243H (rs77381814) single nucleotide polymorphisms in cervical cancer risk.
abstract: Human Papillomavirus (HPV) is the main cause of cervical cancer and its precursor lesions. Transformation may be induced by several mechanisms, including oncogene activation and genome instability. Individual differences in DNA damage recognition and repair have been hypothesized to influence cervical cancer risk. The aim of this study was to evaluate whether the double strand break gene polymorphisms XRCC2 R188H G>A (rs3218536), XRCC3 T241M C>T (rs861539) and R243H G>A (rs77381814) are associated to cervical cancer in Argentine women. A case control study consisting of 322 samples (205 cases and 117 controls) was carried out. HPV DNA detection was performed by PCR and genotyping of positive samples by EIA (enzyme immunoassay). XRCC2 and 3 polymorphisms were determined by pyrosequencing. The HPV-adjusted odds ratio (OR) of XRCC2 188 GG/AG genotypes was OR = 2.4 (CI = 1.1-4.9, p = 0.02) for cervical cancer. In contrast, there was no increased risk for cervical cancer with XRCC3 241 TT/CC genotypes (OR = 0.48; CI = 0.2-1; p = 0.1) or XRCC3 241 CT/CC (OR = 0.87; CI = 0.52-1.4; p = 0.6). Regarding XRCC3 R243H, the G allele was almost fixed in the population studied. In conclusion, although the sample size was modest, the present data indicate a statistical association between cervical cancer and XRCC2 R188H polymorphism. Future studies are needed to confirm these findings.
authors.affiliation: IGEVET-CONICET-Institute of Veterinary Genetics-National Council of Scientific and Technical Investigations, Faculty of Veterinary Genetics, University of La Plata, 60th and 118th Street, PC B1900, La Plata, Buenos Aires, Argentina. perezlo@gmail.com
authors.forename: Luis Orlando
authors.initials: LO
authors.lastname: Pérez
authors.forename: Andrea
authors.initials: A
authors.lastname: Crivaro
authors.forename: Gisela
authors.initials: G
authors.lastname: Barbisan
authors.forename: Lucia
authors.initials: L
authors.lastname: Poleri
authors.forename: Carlos Daniel
authors.initials: CD
authors.lastname: Golijow
mesh_terms: D052685:Alphapapillomavirus / Q000235:genetics / Q000302:isolation & purification; D016022:Case-Control Studies; D004279:DNA, Viral / Q000302:isolation & purification; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D016017:Odds Ratio; D030361:Papillomavirus Infections / Q000235:genetics / Q000473:pathology / Q000821:virology; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000821:virology
chemical_list: D004279:DNA, Viral; D004268:DNA-Binding Proteins; C110901:X-ray repair cross complementing protein 3; C113187:XRCC2 protein, human
references.citation: J Clin Microbiol. 1992 Apr;30(4):987-92
references.pmid: 1315341
references.citation: Cancer Res. 2002 Dec 1;62(23):7075-82
references.pmid: 12460929
references.citation: J Fam Pract. 2009 Sep;58(9 Suppl HPV):S3-7
references.pmid: 19744423
references.citation: Cancer Epidemiol Biomarkers Prev. 2004 Apr;13(4):520-4
references.pmid: 15066914
references.citation: Virology. 2009 Feb 20;384(2):360-8
references.pmid: 19141359
references.citation: Int J Biol Markers. 2011 Oct-Dec;26(4):216-20
references.pmid: 21928248
references.citation: Hum Mol Genet. 2002 Jun 1;11(12):1433-8
references.pmid: 12023985
references.citation: Int J Cancer. 2000 Dec 1;88(5):698-701
references.pmid: 11072236
references.citation: Anal Quant Cytol Histol. 2011 Jun;33(3):175-81
references.pmid: 21980621
references.citation: Int J Radiat Oncol Biol Phys. 2005 Jul 15;62(4):1140-9
references.pmid: 15990020
references.citation: PLoS Pathog. 2009 Apr;5(4):e1000397
references.pmid: 19390600
references.citation: Asian Pac J Cancer Prev. 2011;12(4):963-6
references.pmid: 21790234
references.citation: Hum Mol Genet. 2002 Jun 1;11(12):1399-407
references.pmid: 12023982
references.citation: Eur J Gynaecol Oncol. 2011;32(3):274-9
references.pmid: 21797115
references.citation: Breast Cancer Res Treat. 2008 Dec;112(3):575-9
references.pmid: 18188695
references.citation: J Natl Cancer Inst. 2009 Jan 7;101(1):24-36
references.pmid: 19116388
references.citation: Mutat Res. 1998 Jan 30;412(2):195-205
references.pmid: 9539974
references.citation: Nucleic Acids Res. 1988 Feb 11;16(3):1215
references.pmid: 3344216
references.citation: Cancer Lett. 2005 Mar 10;219(2):125-35
references.pmid: 15723711
references.citation: J Infect Dis. 2009 Jan 1;199(1):20-30
references.pmid: 19012493
references.citation: Int J Gynecol Cancer. 2007 May-Jun;17(3):668-75
references.pmid: 17504380
references.citation: Pathobiology. 2008;75(6):356-63
references.pmid: 19096231
references.citation: J Clin Microbiol. 2005 Jul;43(7):3260-6
references.pmid: 16000445
references.citation: Br J Cancer. 2009 Jan 27;100(2):412-20
references.pmid: 19127255
references.citation: Am J Gastroenterol. 2008 Feb;103(2):360-7
references.pmid: 17986315
references.citation: EMBO J. 2007 Apr 18;26(8):2180-91
references.pmid: 17396148
references.citation: Tohoku J Exp Med. 2011;224(3):201-8
references.pmid: 21701125
references.citation: Hum Mol Genet. 2003 Apr 15;12(8):915-23
references.pmid: 12668615