Polymorphisms of the XRCC1 gene and breast cancer risk in the Mexican population

Abstract

The purpose of this case–control study was to evaluate the association of XRCC1 Arg194Trp and Arg399Gln polymorphisms with susceptibility to breast cancer (BC) in a Mexican population. We analysed DNA samples from 345 BC patients and 352 control subjects by polymerase chain reaction-restriction fragment length polymorphism. The frequency of the 399Gln allele was 23 % in controls and 29 % in patients [OR 1.38 (1.08–1.76); p = 0.01]; genotypes in controls were 60, 36, and 4 % for Arg/Arg, Arg/Gln, and Gln/Gln, respectively, while in patients they were 53, 36, and 11 % [OR 2.71 (1.44–5.10); p = 0.0015 for the Gln/Gln genotype]. Regarding the Arg194Trp polymorphism, the frequency of Trp allele was 15 % in controls and 16 % in patients [OR 1.09 (0.82–1.46); p = 0.54]; the genotype frequencies in controls were 74, 23, and 3 % for Arg/Arg, Arg/Trp and Trp/Trp, respectively, while in patients these were 73, 23, and 4 % [OR 1.41 (0.64–3.14); p = 0.39 for the Trp/Trp genotype]. Allele frequencies were consistent with Hardy–Weinberg equilibrium (p = 0.20 for Arg194Trp and p = 0.54 for Arg399Gln). Our results indicate that the 399Gln polymorphism is associated with an increased risk of BC. Additionally, we found that some covariates increase the risk of BC in Mexican women; namely, antecedent of abortions [OR 3.69 (2.17–6.27); p < 0.001], not breastfeeding [OR 2.46 (1.45–4.18); p = 0.001], family history of BC [OR 15.9 (5.09–50.23); p < 0.001], other type of family cancer [OR 31.5 (12.5–79.3); p < 0.001], alcoholism [OR 17.7 (5.2–60.42); p < 0.001], type 2 diabetes mellitus [OR 2.28 (1.26–4.10); p = 0.007], and contraceptive use [OR 2.28 (1.26–4.10); p < 0.001].

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References

  1. 1.

    Héry C, Ferlay J, Boniol M, Autier P (2008) Changes in breast cancer incidence and mortality in middle aged and elderly women in 28 countries with Caucasian majority populations. Ann Oncol 19(5):1009–1018. doi:10.1093/annonc/mdm593

    Article  PubMed  Google Scholar 

  2. 2.

    Knaul FM, Nigenda G, Lozano R, Arreola-Ornelas H, Langer A, Frenk J (2009) Breast cancer in Mexico: an urgent priority. Salud Publica Mex 51(Suppl 2):s335–s344. doi:10.1590/S0036-36342009000800026

    Article  PubMed  Google Scholar 

  3. 3.

    Yang PS, Yang TL, Liu CL, Wu CW, Shen CY (1997) A case–control study of breast cancer in Taiwan—a low-incidence area. Br J Cancer 75(5):752–756. doi:10.1038/bjc.1997.133

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  4. 4.

    Saadat M, Kohan L, Omidvari S (2008) Genetic polymorphisms of XRCC1 (codon 399) and susceptibility to breast cancer in Iranian women, a case–control study. Breast Cancer Res Treat 111(3):549–553. doi:10.1007/s10549-007-9811-5

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Saadat M, Ansari-Lari M (2009) Polymorphism of XRCC1 (at codon 399) and susceptibility to breast cancer, a meta-analysis of the literatures. Breast Cancer Res Treat 115(1):137–144. doi:10.1007/s10549-008-0051-0

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Sterpone S, Mastellone V, Padua L, Novelli F, Patrono C, Cornetta T, Giammarino D, Donato V, Testa A, Cozzi R (2010) Single-nucleotide polymorphisms in BER and HRR genes, XRCC1 haplotypes and breast cancer risk in Caucasian women. J Cancer Res Clin Oncol 136(4):631–636. doi:10.1007/s00432-010-0791-1

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Ming-Shiean H, Yu JC, Wang HW, Chen ST, Hsiung CN, Ding SL, Wu PE, Shen CY, Cheng CW (2010) Synergistic effects of polymorphisms in DNA repair genes and endogenous estrogen exposure on female breast cancer risk. Ann Surg Oncol 17(3):760–771. doi:10.1245/s10434-009-0802-0

    Article  PubMed  Google Scholar 

  8. 8.

    Wang YG, Zheng TY (2012) XRCC1—77> polymorphism and cancer risk: a meta-analysis. Asian Pac J Cancer Prev 13(1):111–115. doi:10.7314/APJCP.2012.13.1.111

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Hubbard TJP, Aken BL, Ayling S, Ballester B, Beal K, Bragin E, Brent S, Chen Y, Clapham P, Clarke L, Coates G, Fairley S, Fitzgerald S, Fernandez-Banet J, Gordon L, Graf S, Haider S, Hammond M, Holland R, Howe K, Jenkinson A, Johnson N, Kahari A, Keefe D, Keenan S, Kinsella R, Kokocinski F, Kulesha E, Lawson D, Longden I, Megy K, Meidl P, Overduin B, Parker A, Pritchard B, Rios D, Schuster M, Slater G, Smedley D, Spooner W, Spudich G, Trevanion S, Vilella A, Vogel J, White S, Wilder S, Zadissa A, Birney E, Cunningham F, Curwen V, Durbin R, Fernandez-Suarez XM, Herrero J, Kasprzyk A, Proctor G, Smith J, Searle S, Flicek P (2009) Ensembl 2009. Nucleic Acids Res 37:D690–D697. doi:10.1093/nar/gkn828

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  10. 10.

    Lamerdin J, Montgomery M, Stilwagen S, Tebbs R, Scheidecker L, Brookman KW, Thompson LH, Carrano AV (1995) Genomic sequence comparison of the human and mouse XRCC1 DNA repair gene regions. Genomics 25(2):547–554. doi:10.1016/0888-7543(95)80056-R

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Duell E, Millikan R, Pittman G, Winkel S, Lunn R, Tse C, Eaton A, Mohrenweiser H, Newman B, Bell D (2001) Polymorphisms in the DNA repair gene XRCC1 and breast cancer. Cancer Epidemiol Biomarkers Prev 10(3):217–222

    CAS  PubMed  Google Scholar 

  12. 12.

    Han J, Hankinson SE, De Vivo I, Spiegelman D, Tamimi RM, Mohrenweiser HW, Colditz GA, Hunter DJ (2003) A prospective study of XRCC1 haplotypes and their interaction with plasma carotenoids on breast cancer risk. Cancer Res 63(23):8536–8541

    CAS  PubMed  Google Scholar 

  13. 13.

    Au WW, Salama SA, Sierra-Torres CH (2003) Functional characterization of polymorphisms in DNA repair genes using cytogenetic challenge assays. Environ Health Perspect 111(15):1843–1850. doi:10.1289/txg.6632

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  14. 14.

    Shu XO, Cai Q, Gao YT, Wen W, Jin F, Zheng W (2003) A population-based case–control study of the Arg399Gln polymorphism in DNA repair gene XRCC1 and risk of breast cancer. Cancer Epidemiol Biomarkers Prev 12(12):1462–1467

    CAS  PubMed  Google Scholar 

  15. 15.

    Deligezer U, Dalay N (2004) Association of the XRCC1 gene polymorphisms with cancer risk in Turkish breast cancer patients. Exp Mol Med 36(6):572–575. doi:10.1038/emm.2004.73

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Figueiredo JC, Knight JA, Briollais L, Andrulis IL, Ozcelik H (2004) Polymorphisms XRCC1-R399Q and XRCC3-T241M and the risk of breast cancer at the ontario site of the breast cancer family registry. Cancer Epidemiol Biomarkers Prev 13(4):583–591

    CAS  PubMed  Google Scholar 

  17. 17.

    Metsola K, Kataja V, Sillanpää P, Siivola P, Heikinheimo L, Eskelinen M, Kosma VM, Uusitupa M, Hirvonen A (2005) XRCC1 and XPD genetic polymorphisms, smoking and breast cancer risk in a Finnish case–control study. Breast Cancer Res 7(6):987–997. doi:10.1186/bcr1333

    Article  Google Scholar 

  18. 18.

    Patel AV, Calle EE, Pavluck AL, Feigelson HS, Thun MJ, Rodriguez C (2005) A prospective study of XRCC1 (X-ray cross-complementing group 1) polymorphisms and breast cancer risk. Breast Cancer Res 7(6):1168–1173. doi:10.1186/bcr1355

    Article  Google Scholar 

  19. 19.

    Pachkowski BF, Winkel S, Kubota Y, Swenberg JA, Millikan RC, Nakamura J (2006) XRCC1 genotype and breast cancer: functional studies and epidemiologic data show interactions between XRCC1 codon 280 His and smoking. Cancer Res 66(5):2860–2868. doi:10.1158/0008-5472

    CAS  Article  PubMed  Google Scholar 

  20. 20.

    Thyagarajan B, Anderson KE, Folsom AR, Jacobs DR Jr, Lynch CF, Bargaje A, Khaliq W, Gross MD (2006) No association between XRCC1 and XRCC3 gene polymorphisms and breast cancer risk: Iowa women’s health study. Cancer Detect Prev 30(4):313–321. doi:10.1016/j.cdp.206.07.002

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Zhai X, Liu J, Hu Z, Wang S, Qing J, Wang X, Jin G, Gao J, Wang X, Shen H (2006) Polymorphisms of ADPRT Val762Ala and XRCC1 Arg399Glu and risk of breast cancer in Chinese women: a case control analysis. Oncol Rep 15(1):247–252. doi:10.3892/or.15.1.247

    CAS  PubMed  Google Scholar 

  22. 22.

    Zhang Y, Newcomb PA, Egan KM, Titus-Ernstoff L, Chanock S, Welch R, Brinton LA, Lissowska J, Bardin-Mikolajczak A, Peplonska B, Szeszenia-Dabrowska N, Zatonski W, Garcia-Closas M (2006) Genetic polymorphisms in base-excision repair pathway genes and risk of breast cancer. Cancer Epidemiol Biomarkers Prev 15(2):353–358. doi:10.1158/1055-9965.EPI-05-0653

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    Silva SN, Moita R, Azevedo AP, Gouveia R, Manita I, Pina JE, Rueff J, Gaspar J (2007) Menopausal age and XRCC1 gene polymorphisms: role in breast cancer risk. Cancer Detect Prev 3(4):303–309. doi:10.1016/j.cdp.2007.07.001

    Article  Google Scholar 

  24. 24.

    Ali MF, Meza JL, Rogan EG, Chakravarti D (2008) Prevalence of BER gene polymorphisms in sporadic breast cancer. Oncol Rep 19(4):1033–1038. doi:10.3892/or.19.4.1033

    CAS  PubMed  Google Scholar 

  25. 25.

    Dufloth RM, Arruda A, Heinrich JKR, Schmitt F, Zeferino LC (2008) The investigation of DNA repair polymorphisms with histopathological characteristics and hormone receptors in a group of Brazilian women with breast cancer. Genet Mol Res 7(3):574–582. doi:10.4238/vol7-3gmr376

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Loizidou MA, Michael T, Neuhausen SL, Newbold RF, Marcou Y, Kakouri E, Daniel M, Papadopoulos P, Malas S, Kyriacou K, Hadjisavvas A (2008) Genetic polymorphisms in the DNA repair genes XRCC1, XRCC2 and XRCC3 and risk of breast cancer in Cyprus. Breast Cancer Res Treat 112(3):575–579. doi:10.1007/s10549-007-9881-4

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    Smith TR, Levine EA, Freimanis RI, Akman SA, Allen GO, Hoang KN, Liu-Mares W, Hu JJ (2008) Polygenic model of DNA repair genetic polymorphisms in human breast cancer risk. Carcinogenesis 29(11):2132–2138. doi:10.1093/carcin/bgn193

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  28. 28.

    Falagan-Lotsch P, Rodrigues MS, Esteves V, Vieira R, Amendola LC, Pagnoncelli D, Paixão JC, Gallo CV (2009) XRCC1 gene polymorphisms in a population sample and in women with a family history of breast cancer from Rio de Janeiro (Brazil). Genet Mol Biol 32(2):255–259. doi:10.1590/S1415-47572009000200008

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  29. 29.

    Wu K, Su D, Lin K, Luo J, Au WW (2011) XRCC1 Arg399Gln gene polymorphism and breast cancer risk: a meta-analysis based on case–control studies. Asian Pac J Cancer Prev 12(9):2237–2243

    PubMed  Google Scholar 

  30. 30.

    Al Mutairi FM, Alanazi M, Shalaby M, Alabdulkarim HA, Pathan AA, Parine NR (2013) Association of XRCC1 gene polymorphisms with breast cancer susceptibility in Saudi patients. Asian Pac J Cancer Prev 14(6):3809–3813. doi:10.7314/APJCP.2013.14.6.3809

    Article  PubMed  Google Scholar 

  31. 31.

    Przybylowska-Sygut K, Stanczyk M, Kusinska R, Kordek R, Majsterek I (2013) Association of the Arg194Trp and the Arg399Gln polymorphisms of the XRCC1 gene with risk occurrence and the response to adjuvant therapy among Polish women with breast cancer. Clin Breast Cancer 13(1):61–68. doi:10.1016/j.clbc.2012.09.019

    CAS  Article  PubMed  Google Scholar 

  32. 32.

    Butkiewicz D, Rusin M, Enewold L, Shields PG, Chorazy M, Harris CC (2001) Genetic polymorphisms in DNA repair genes and risk of lung cancer. Carcinogenesis 22(4):593–597. doi:10.1093/carcin/22.4.593

    CAS  Article  PubMed  Google Scholar 

  33. 33.

    Zhang Z, Wan J, Jin X, Jin T, Shen H, Lu D, Xia Z (2005) Genetic polymorphisms in XRCC1, APE1, ADPRT, XRCC2 and XRCC3 and risk of chronic benzene poisoning in a Chinese occupational population. Cancer Epidemiol Biomarkers Prev 14(11 Pt 1):2614–2619. doi:10.1158/1055-9965.EPI-05-0143

    CAS  Article  PubMed  Google Scholar 

  34. 34.

    Gustincich S, Manfioletti G, Del Sal G, Schneider C, Carninci P (1991). A fast method for high-quality genomic DNA extraction from whole human blood. Biotechniques 11(3):298–300,302

  35. 35.

    Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16(3):1215

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  36. 36.

    Roberts MR, Shields PG, Ambrosone CB, Nie J, Marian C, Krishnan SS, Goerlitz DS, Modali R, Seddon M, Lehman T, Amend KL, Trevisan M, Edge SB, Freudenheim JL (2011) Single-nucleotide polymorphisms in DNA repair and association whit breast cancer risk in the web study. Carcinogenesis 32(8):1223–1230. doi:10.1093/carcin/bgr096

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  37. 37.

    Ritte R, Tikk K, Lukanova A, Tjønneland A, Olsen A, Overvad K, Dossus L, Fournier A, Clavel-Chapelon F, Grote V, Boeing H, Aleksandrova K, Trichopoulou A, Lagiou P, Trichopoulos D, Palli D, Berrino F, Mattiello A, Tumino R, Sacerdote C, Quirós JR, Buckland G, Molina-Montes E, Chirlaque MD, Ardanaz E, Amiano P, Bueno-de-Mesquita HB, van Gils CH, Peeters PH, Wareham N, Khaw KT, Key TJ, Travis RC, Weiderpass E, Dumeaux V, Lund E, Sund M, Andersson A, Romieu I, Rinaldi S, Vineis P, Merritt MA, Riboli E, Kaaks R (2013) Reproductive factors and risk of hormone receptor positive and negative breast cancer: a cohort study. BMC Cancer 13:584. doi:10.1186/1471-2407-13-584

    PubMed Central  Article  PubMed  Google Scholar 

  38. 38.

    Lipworth L, Bailey LR, Trichopoulos D (2000) History of breast-feeding in relation to breast cancer risk: a review of the epidemiologic literature. J Natl Cancer Inst 92(4):302–312. doi:10.1093/jnci/92.4.302

    CAS  Article  PubMed  Google Scholar 

  39. 39.

    Akbari A, Razzaghi Z, Homaee F, Khayamzadeh M, Movahedi M, Akbari ME (2011) Parity and breastfeeding are preventive measures against breast cancer in Iranian women. Breast Cancer 18(1):51–55. doi:10.1007/s12282-010-0203-z

    Article  PubMed  Google Scholar 

  40. 40.

    Aguilar Cordero MJ, González Jiménez E, Álvarez Ferre J, Padilla López CA, Mur Villar N, García López PA, Valenza Peña MC (2010) Breast feeding: an effective method to prevent breast cancer. Nutr Hosp 25(6):954–958. doi:10.3305/nh.2010.25.6.4994

    PubMed  Google Scholar 

  41. 41.

    Parkin DM (2011) Cancers attributable to reproductive factors in the UK in 2010. Br J Cancer 105(Suppl 2):s73–s76. doi:10.1038/bjc.2011.488

    PubMed Central  Article  PubMed  Google Scholar 

  42. 42.

    Parameshwari P, Muthukumar K, Jennifer HG (2013) A population based case control study on breast cancer and the associated risk factors in a rural setting in Kerala, southern India. J Clin Diagn Res 7(9):1913–1916. doi:10.7860/JCDR/2013/5830.3356

    PubMed Central  CAS  PubMed  Google Scholar 

  43. 43.

    Negri E, Braga C, La Vecchia C, Levi F, Talamini R, Franceschi S (1996) Lactation and the risk of breast cancer in an Italian population. Int J Cancer 67(2):161–164. doi:10.1002/(SICI)1097-0215(19960717)67:2<161::AID-IJC1>3.0.CO;2-R

    CAS  Article  PubMed  Google Scholar 

  44. 44.

    Andrieu N, Goldgar DE, Easton DF, Rookus M, Brohet R, Antoniou AC, Peock S, Evans G, Eccles D, Douglas F, Noguès C, Gauthier-Villars M, Chompret A, Van Leeuwen FE, Kluijt I, Benitez J, Arver B, Olah E, Chang-Claude J, EMBRACE, GENEPSO, GEO-HEBON, IBCCS Collaborators Group (2006) Pregnancies, breast-feeding, and breast cancer risk in the international BRCA1/2 carrier cohort study (IBCCS). J Natl Cancer Inst 98(8):535–544. doi:10.1093/jnci/djj132

    PubMed Central  Article  PubMed  Google Scholar 

  45. 45.

    Narod SA (2006) Modifiers of risk of hereditary breast cancer. Oncogene 25(43):5832–5836. doi:10.1038/sj.onc.1209870

    CAS  Article  PubMed  Google Scholar 

  46. 46.

    Ilic M, Vlajinac H, Marinkovic J, Sipetic-Grujicic S (2013) Abortion and breast cancer: case–control study. Tumori 99(4):452–457. doi:10.1700/1361.15093

    PubMed  Google Scholar 

  47. 47.

    Nicolucci A (2010) Epidemiological aspects of neoplasms in diabetes. Acta Diabetol 47(2):87–95. doi:10.1007/s00592-010-0187-3

    Article  PubMed  Google Scholar 

  48. 48.

    Onitilo AA, Stankowski RV, Berg RL, Engel JM, Glurich I, Williams GM (2014) Type 2 diabetes mellitus, glycemic control, and cancer risk. Eur J Cancer Prev 23(2):134–140. doi:10.1097/CEJ.0b013e3283656394

    CAS  Article  PubMed  Google Scholar 

  49. 49.

    Oyesanmi O, Snyder D, Sullivan N, Reston J, Treadwell J, Schoelles KM (2010) Alcohol consumption and cancer risk: understanding possible causal mechanisms for breast and colorectal cancers. Evid Rep Technol Assess 197:1–151

    Google Scholar 

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Acknowledgments

Research supported by Universidad Autónoma de Tamaulipas through grant UAT10-SAL-0306.

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There are no conflicts of interest.

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The study was approved by the institutional Ethics Committee, and written consent was obtained from each participant before enrolling into the study, together with a complete medical history.

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Correspondence to Evelia Leal-Ugarte.

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Macías-Gómez, N.M., Peralta-Leal, V., Meza-Espinoza, J.P. et al. Polymorphisms of the XRCC1 gene and breast cancer risk in the Mexican population. Familial Cancer 14, 349–354 (2015). https://doi.org/10.1007/s10689-015-9787-y

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Keywords

  • Breast cancer
  • XRCC1 gene
  • Polymorphisms
  • Risk factors