Genetic polymorphisms in DNA repair genes, XRCC1 (Arg399Gln) and XRCC3 (Thr241Met), may affect their DNA repair capacity leading to individual variation in breast cancer susceptibility among Bangladeshi females.
The case–control study comprised 121 breast cancer patients and 133 healthy controls. Genomic DNA isolated from peripheral blood was genotyped for target SNPs using PCR-RFLP method.
For XRCC1, heterozygous Arg/Gln and homozygous Gln/Gln genotypes showed 1.78-fold (95% CI 1.0084 to 3.1442, p = 0.0467) and 2.41-fold (95% CI 1.0354 to 5.5914, p = 0.0413) increased risk of breast cancer, respectively, when compared with Arg/Arg genotype. The presence of any XRCC1 Gln showed association with 1.93-fold increased risk. The variant Gln allele was associated with increased risk of breast cancer (95% CI 1.1885 to 2.6805, p = 0.0052). For XRCC3, Thr/Met heterozygous and combined Thr/Met + Met/Met genotypes were associated with 1.85-fold (95% CI 1.0815 to 3.1834, p = 0.0248) and 1.89-fold (95% CI 1.1199 to 3.1908, p = 0.0171) higher risk, respectively, compared to Thr/Thr genotypes. The variant Met allele showed significant association with increased breast cancer susceptibility. Among cases genotype frequencies were significantly different in patients with age 55 or above, and with menopause and diabetes.
XRCC1 (Arg399Gln) and XRCC3 (Thr241Met) polymorphisms may be associated with increased breast cancer risk in Bangladeshi females.
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The datasets during and/or analyzed during the current study are available from the corresponding author on reasonable request.
Ferlay J, Ervik M, Lam F et al (2018) Global cancer observatory: cancer today. International Agency for Research on Cancer, Lyon
McGuire A, Brown JAL, Malone C et al (2015) Effects of age on the detection and management of breast cancer. Cancers (Basel) 7:908–929
Bray F, Ferlay J, Soerjomataram I et al (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424
Ferlay J, Soerjomataram I, Dikshit R et al (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J cancer 136:E359–E386
Wood RD, Mitchell M, Sgouros J, Lindahl T (2001) Human DNA repair genes. Science 291:1284–1289
Kubota Y, Nash RA, Klungland A et al (1996) Reconstitution of DNA base excision-repair with purified human proteins: interaction between DNA polymerase beta and the XRCC1 protein. EMBO J 15:6662–6670
Tudek B (2007) Base excision repair modulation as a risk factor for human cancers. Mol Asp Med 28:258–275
Shen H, Wang X, Hu Z et al (2004) Polymorphisms of DNA repair gene XRCC3 Thr241Met and risk of gastric cancer in a Chinese population. Cancer Lett 206:51–58
Figueiredo JC, Knight JA, Briollais L et al (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 Prev Biomark 13:583–591
Webb PM, Hopper JL, Newman B et al (2005) Double-strand break repair gene polymorphisms and risk of breast or ovarian cancer. Cancer Epidemiol Prev Biomark 14:319–323
Khlifi R, Kallel I, Hammami B et al (2014) DNA repair gene polymorphisms and risk of head and neck cancer in the Tsunisian population. J Oral Pathol Med 43:217–224
Duell EJ, Millikan RC, Pittman GS et al (2001) Polymorphisms in the DNA repair gene XRCC1 and breast cancer. Cancer Epidemiol Prev Biomark 10:217–222
Han J, Hankinson SE, De Vivo I et al (2003) A prospective study of XRCC1 haplotypes and their interaction with plasma carotenoids on breast cancer risk. Cancer Res 63:8536–8541
Smith TR, Levine EA, Perrier ND et al (2003) DNA-repair genetic polymorphisms and breast cancer risk. Cancer Epidemiol Prev Biomark 12:1200–1204
Shen J, Gammon MD, Terry MB et al (2005) Polymorphisms in XRCC1 modify the association between polycyclic aromatic hydrocarbon-DNA adducts, cigarette smoking, dietary antioxidants, and breast cancer risk. Cancer Epidemiol Prev Biomark 14:336–342
Patel AV, Calle EE, Pavluck AL et al (2005) A prospective study of XRCC1(X-ray cross-complementing group 1) polymorphisms and breast cancer risk. Breast Cancer Res 7:R1168. https://doi.org/10.1186/bcr1355
Bu D, Tomlinson G, Lewis CM et al (2006) An intronic polymorphism associated with increased XRCC1 expression, reduced apoptosis and familial breast cancer. Breast Cancer Res Treat 99:257–265
Thyagarajan B, Anderson KE, Folsom AR et al (2006) No association between XRCC1 and XRCC3 gene polymorphisms and breast cancer risk: Iowa Women’s Health Study. Cancer Detect Prev 30:313–321
Sangrajrang S, Schmezer P, Burkholder I et al (2007) The XRCC3 Thr241Met polymorphism and breast cancer risk: a case–control study in a Thai population. Biomarkers 12:523–532
Costa S, Pinto D, Pereira D et al (2007) DNA repair polymorphisms might contribute differentially on familial and sporadic breast cancer susceptibility: a study on a Portuguese population. Breast Cancer Res Treat 103:209–217
Economopoulos KP, Sergentanis TN (2010) XRCC3 Thr241Met polymorphism and breast cancer risk: a meta-analysis. Breast Cancer Res Treat 121:439–443
World Medical Association (2013) World medical association declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA 310(20):2191–2194. https://doi.org/10.1001/jama.2013.281053
Daly AK, Monkman SC, Smart J et al (1998) Analysis of cytochrome P450 polymorphisms. Cytochrome P450 protocols. Springer, New York, pp 405–422
Saiki RK, Gelfand DH, Stoffel S et al (1988) Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 239:487–491
Siegel RL, Miller KD, Jemal A (2016) Cancer statistics. CA Cancer J Clin 66:7–30
Landi S (2009) Genetic predisposition and environmental risk factors to pancreatic cancer: a review of the literature. Mutat Res 681:299–307
Chu D, Kohlmann W, Adler DG (2010) Identification and screening of individuals at increased risk for pancreatic cancer with emphasis on known environmental and genetic factors and hereditary syndromes. JOP J Pancreas 11:203–212
Lowenfels AB, Maisonneuve P (2003) Environmental factors and risk of pancreatic cancer. Pancreatology 3:1–8
Wong H, Wilson DM (2005) XRCC1 and DNA polymerase β interaction contributes to cellular alkylating-agent resistance and single-strand break repair. J Cell Biochem 95:794–804
Liu N, Lamerdin JE, Tebbs RS et al (1998) XRCC2 and XRCC3, new human Rad51-family members, promote chromosome stability and protect against DNA cross-links and other damages. Mol Cell 1:783–793
Pierce AJ, Johnson RD, Thompson LH, Jasin M (1999) XRCC3 promotes homology-directed repair of DNA damage in mammalian cells. Genes Dev 13:2633–2638
Smolarz B, Makowska M, Samulak D et al (2014) Single nucleotide polymorphisms (SNPs) of ERCC2, hOGG1, and XRCC1 DNA repair genes and the risk of triple-negative breast cancer in Polish women. Tumor Biol 35:3495–3502
Han J, Haiman C, Niu T et al (2009) Genetic variation in DNA repair pathway genes and premenopausal breast cancer risk. Breast Cancer Res Treat 115:613–622
Wang L, Wang G, Lu C et al (2012) Contribution of the-160C/A polymorphism in the E-cadherin promoter to cancer risk: a meta-analysis of 47 case-control studies. PLoS ONE 7:e40219
Jeanes A, Gottardi CJ, Yap AS (2008) Cadherins and cancer: how does cadherin dysfunction promote tumor progression? Oncogene 27:6920
Popanda O, Tan X-L, Ambrosone CB et al (2006) Genetic polymorphisms in the DNA double-strand break repair genes XRCC3, XRCC2, and NBS1 are not associated with acute side effects of radiotherapy in breast cancer patients. Cancer Epidemiol Prev Biomark 15:1048–1050
Kuschel B, Auranen A, McBride S et al (2002) Variants in DNA double-strand break repair genes and breast cancer susceptibility. Hum Mol Genet 11:1399–1407
Rao KS, Paul A, Kumar ASA et al (2014) Allele and genotype distributions of DNA repair gene polymorphisms in South Indian healthy population. Biomark Cancer 6:BIC-S19681
Takeshita H, Fujihara J, Yasuda T, Kimura-Kataoka K (2015) Worldwide distribution of four SNPs in X-ray and repair and cross-complementing group 1 (XRCC1). Clin Transl Sci 8:347–350
Goričar K, Kovač V, Dolžan V (2017) Clinical-pharmacogenetic models for personalized cancer treatment: application to malignant mesothelioma. Sci Rep 7:46537
Sterpone S, Mastellone V, Padua L et al (2010) Single-nucleotide polymorphisms in BER and HRR genes, XRCC1 haplotypes and breast cancer risk in Caucasian women. J Cancer Res Clin Oncol 136:631–636
Chacko P, Rajan B, Joseph T et al (2005) Polymorphisms in DNA repair gene XRCC1 and increased genetic susceptibility to breast cancer. Breast Cancer Res Treat 89:15–21
Luo H, Li Z, Qing Y et al (2014) Single nucleotide polymorphisms of DNA base-excision repair genes (APE1, OGG1 and XRCC1) associated with breast cancer risk in a Chinese population. Asian Pac J Cancer Prev 15:1133–1140
Ramadan RA, Desouky LM, Elnaggar MA et al (2014) Association of DNA repair genes XRCC1 (Arg399Gln),(Arg194Trp) and XRCC3 (Thr241Met) polymorphisms with the risk of breast cancer: a case–control study in Egypt. Genet Test Mol Biomark 18:754–760
Shadrina AS, Ermolenko NA, Boyarskikh UA et al (2016) Polymorphisms in DNA repair genes and breast cancer risk in Russian population: a case–control study. Clin Exp Med 16:21–28
Syamala VS, Syamala V, Sreedharan H et al (2009) Contribution of XPD (Lys751Gln) and XRCC1 (Arg399Gln) polymorphisms in familial and sporadic breast cancer predisposition and survival: an Indian report. Pathol Oncol Res 15:389
Smolarz B, Michalska MM, Samulak D et al (2019) Polymorphism of DNA repair genes in breast cancer. Oncotarget 10:527
Romanowicz H, Smolarz B, Baszczyński J et al (2010) Genetics polymorphism in DNA repair genes by base excision repair pathway (XRCC1) and homologous recombination (XRCC2 and RAD51) and the risk of breast carcinoma in the Polish population. Pol J Pathol 61:206–212
Macías-Gómez NM, Peralta-Leal V, Meza-Espinoza JP et al (2015) Polymorphisms of the XRCC1 gene and breast cancer risk in the Mexican population. Fam Cancer 14:349–354
Romanowicz H, Pyziak Ł, Jabłoński F et al (2017) Analysis of DNA repair genes polymorphisms in breast cancer. Pathol Oncol Res 23:117–123
Roberts MR, Shields PG, Ambrosone CB et al (2011) Single-nucleotide polymorphisms in DNA repair genes and association with breast cancer risk in the web study. Carcinogenesis 32:1223–1230
Shen MR, Jones IM, Mohrenweiser H (1998) Nonconservative amino acid substitution variants exist at polymorphic frequency in DNA repair genes in healthy humans. Cancer Res 58:604–608
Lunn RM, Langlois RG, Hsieh LL et al (1999) XRCC1 polymorphisms: effects on aflatoxin B1-DNA adducts and glycophorin a variant frequency. Cancer Res 59:2557–2561
Duell EJ, Wiencke JK, Cheng T-J et al (2000) Polymorphisms in the DNA repair genes XRCC1 and ERCC2 and biomarkers of DNA damage in human blood mononuclear cells. Carcinogenesis 21:965–971
Al Mutairi FM, Alanazi M, Shalaby M et al (2013) Association of XRCC1 gene polymorphisms with breast cancer susceptibility in Saudi patients. Asian Pac J Cancer Prev 14:3809–3813
Hussien Y, Gharib A, Karam R, Elsawy W (2011) Impact of DNA repair gene polymorphisms (XPD and XRCC1) on the risk of breast cancer in Egyptian female patients. Bull Egypt Soc Physiol Sci 31:91–106
Metsola K, Kataja V, Sillanpää P et al (2005) XRCC1 and XPD genetic polymorphisms, smoking and breast cancer risk in a Finnish case-control study. Breast Cancer Res 7:R987
Zipprich J, Terry MB, Brandt-Rauf P et al (2010) XRCC1 polymorphisms and breast cancer risk from the New York Site of the breast cancer family Registry: a family-based case-control study. J Carcinog 9:4
Kim S-U, Park SK, Yoo K-Y et al (2002) XRCC1 genetic polymorphism and breast cancer risk. Pharmacogenet Genom 12:335–338
Moghaddam AS, Nazarzadeh M, Moghaddam HS et al (2016) XRCC1 gene polymorphisms and breast cancer risk: a systematic review and meta-analysis study. Asian Pac J Cancer Prev 17:323–335
Wu K, Su D, Lin K et al (2011) XRCC1 Arg399Gln gene polymorphism and breast cancer risk: a meta-analysis based on case-control studies. Asian Pac J Cancer Prev 12:2237–2243
Saadat M (2010) Haplotype analysis of XRCC1 (at codons 194 and 399) and susceptibility to breast cancer, a meta-analysis of the literatures. Breast Cancer Res Treat 124:785–791
Zdzienicka MZ (1999) Mammalian X-ray-sensitive mutants which are defective in non-homologous (illegitimate) DNA double-strand break repair. Biochimie 81:107–116
Thacker J, Zdzienicka MZ (2004) The XRCC genes: expanding roles in DNA double-strand break repair. DNA Repair (Amst) 3:1081–1090
Brenneman MA, Weiss AE, Nickoloff JA, Chen DJ (2000) XRCC3 is required for efficient repair of chromosome breaks by homologous recombination. Mutat Res Repair 459:89–97
Richardson C (2005) RAD51, genomic stability, and tumorigenesis. Cancer Lett 218:127–139
García-Closas M, Egan KM, Newcomb PA et al (2006) Polymorphisms in DNA double-strand break repair genes and risk of breast cancer: two population-based studies in USA and Poland, and meta-analyses. Hum Genet 119:376
Bastos HN, Antao MR, Silva SN et al (2009) Association of polymorphisms in genes of the homologous recombination DNA repair pathway and thyroid cancer risk. Thyroid 19:1067–1075
Sturgis EM, Zhao C, Zheng R, Wei Q (2005) Radiation response genotype and risk of differentiated thyroid cancer: a case-control analysis. Laryngoscope 115:938–945
Qureshi Z, Mahjabeen I, Baig RM, Kayani MA (2014) Correlation between selected XRCC2, XRCC3 and RAD51 gene polymorphisms and primary breast cancer in women in Pakistan. Asian Pac J Cancer Prev 15:10225–10229
Smolarz B, Makowska M, Samulak D et al (2015) Association between single nucleotide polymorphisms (SNPs) of XRCC2 and XRCC3 homologous recombination repair genes and triple-negative breast cancer in Polish women. Clin Exp Med 15:151–157
Krupa R, Synowiec E, Pawlowska E et al (2009) Polymorphism of the homologous recombination repair genes RAD51 and XRCC3 in breast cancer. Exp Mol Pathol 87:32–35
Sobczuk A, Romanowicz-Makowska H, Fiks T et al (2009) XRCC1 and XRCC3 DNA repair gene polymorphisms in breast cancer women from the Lodz region of Poland. Polish J Pathol 60:76–80
Su C-H, Chang W-S, Hu P-S et al (2015) Contribution of DNA double-strand break repair gene XRCC3 genotypes to triple-negative breast cancer risk. Cancer Genom-Proteom 12:359–367
Loizidou MA, Michael T, Neuhausen SL et al (2008) Genetic polymorphisms in the DNA repair genes XRCC1, XRCC2 and XRCC3 and risk of breast cancer in Cyprus. Breast Cancer Res Treat 112:575–579
Ali AM, AbdulKareem H, Al Anazi M et al (2016) Polymorphisms in DNA repair gene XRCC3 and susceptibility to breast cancer in Saudi females. Biomed Res Int. https://doi.org/10.1155/2016/8721052
Devi KR, Ahmed J, Narain K et al (2017) DNA repair mechanism gene, XRCC1A (Arg194Trp) but not XRCC3 (Thr241Met) polymorphism increased the risk of breast cancer in premenopausal females: a case–control study in northeastern Region of India. Technol Cancer Res Treat 16:1150–1159
Al ZMS, Zavaglia K, Mazanti C et al (2017) Polymorphisms and mutations in GSTP1, RAD51, XRCC1 and XRCC3 genes in breast cancer patients. Int J Biol Markers 32:337–343
Jordan S, Lim L, Vilainerun D et al (2009) Breast cancer in the Thai Cohort Study: an exploratory case-control analysis. The Breast 18:299–303
The authors express their gratitude to the Pharmacy Discipline of Khulna University, Bangladesh for laboratory facilities. We are thankful to the staff, nurses, physicians, and the authority of the National Institute of Cancer Research and Hospital (NICRH) of Dhaka, Khulna Medical College Hospital. Khulna Bangladesh for their kind permission and assistance to collect blood samples from breast cancer patients and allowing relevant clinical data. We also express our thankful gratitude to the Ministry of Science and Technology of the Government of the People’s Republic of Bangladesh and Khulna University Research Cell for their partial financial support to conduct the study.
The authors received partial financial support from the Ministry of Science and Technology of the Government of the People’s Republic of Bangladesh and also from Khulna University Research Cell.
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The authors declare no potential conflict of interest with regard to research, authorship, and/or publication of this manuscript.
The study was conducted according to the Helsinki declaration and its subsequent revisions and the protocol was approved by the Ethical Committee of the hospital.
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Howlader, N.R., Rahman, M.M., Hossain, M.A. et al. Genetic polymorphisms in DNA repair genes XRCC1 and 3 are associated with increased risk of breast cancer in Bangladeshi population. Breast Cancer Res Treat 182, 739–750 (2020). https://doi.org/10.1007/s10549-020-05738-8
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