Rad51 paralogs and the risk of unselected breast cancer: A case-control study

1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA. Cancer J. Clin. 2015;65(2):87–108 doi: 10.3322/caac.21262 25651787

2. Sekhar D, Pooja S, Kumar S, Rajender S. RAD51 135G>C substitution increases breast cancer risk in an ethnic-specific manner: a meta-analysis on 21,236 cases and 19,407 controls. Sci. Rep. 2015;5(1):11588

3. Stratton MR, Rahman N. The emerging landscape of breast cancer susceptibility. Nat. Genet. 2008;40(1):17–22 doi: 10.1038/ng.2007.53 18163131

4. Turnbull C, Rahman N. Genetic predisposition to breast cancer: past, present, and future. Annu. Rev. Genomics Hum. Genet. 2008;9:321–45 doi: 10.1146/annurev.genom.9.081307.164339 18544032

5. Levy-Lahad E. Fanconi anemia and breast cancer susceptibility meet again. Nat.Genet. 2010;42(5):368–9 doi: 10.1038/ng0510-368 20428093

6. Rahman N, Seal S, Thompson D, Kelly P, Renwick A, Elliott A, et al. PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene. Nat. Genet. 2007;39(2):165–7 doi: 10.1038/ng1959 17200668

7. Seal S, Thompson D, Renwick A, Elliott A, Kelly P, Barfoot R, et al. Truncating mutations in the Fanconi anemia J gene BRIP1 are low-penetrance breast cancer susceptibility alleles. Nat. Genet. 2006;38(11):1239–41 doi: 10.1038/ng1902 17033622

8. Ding S-L, Yu J-C, Chen S-T, Hsu G-C, Kuo S-J, Lin YH, et al. Genetic variants of BLM interact with RAD51 to increase breast cancer susceptibility. Carcinogenesis 2009;30(1):43–9 doi: 10.1093/carcin/bgn233 18974064

9. Sun H, Bai J, Chen F, Jin Y, Yu Y, Jin L, et al. RAD51 G135C polymorphism is associated with breast cancer susceptibility: a meta-analysis involving 22,399 subjects. Breast Cancer Res. Treat. 2011;125(1):157–61 doi: 10.1007/s10549-010-0922-z 20454923

10. Zhang B-B, Wang D-G, Xuan C, Sun G-L, Deng K-F. Genetic 135G/C polymorphism of RAD51 gene and risk of cancer: a meta-analysis of 28,956 cases and 28,372 controls. Fam. Cancer 2014;13(4):515–26 doi: 10.1007/s10689-014-9729-0 24859942

11. Ripperger T, Gadzicki D, Meindl A, Schlegelberger B. Breast cancer susceptibility: current knowledge and implications for genetic counselling. Eur. J. Hum. Genet. 2009;17(6):722–31 doi: 10.1038/ejhg.2008.212 19092773

12. Masson J, Tarsounas MC, Stasiak AZ, Stasiak A, Shah R, Michael J, et al. Identification and purification of two distinct complexes containing the five RAD51 paralogs. Genes Dev. 2001;15(24):3296–307 doi: 10.1101/gad.947001 11751635

13. Thacker J. The RAD51 gene family, genetic instability and cancer. Cancer Lett. 2005;219(2):125–35 doi: 10.1016/j.canlet.2004.08.018 15723711

14. Badie S, Liao C, Thanasoula M, Barber P, Hill MA, Tarsounas M. RAD51C facilitates checkpoint signaling by promoting CHK2 phosphorylation. J.Cell Biol. 2009;185(4):587–600 doi: 10.1083/jcb.200811079 19451272

15. Liu Y, Masson JY, Shah R, O’Regan P, West SC. RAD51C is required for Holliday junction processing in mammalian cells. Science. 2004;303(5655):243–6 doi: 10.1126/science.1093037 14716019

16. Somyajit K, Subramanya S, Nagaraju G. Distinct roles of FANCO/RAD51C protein in DNA damage signaling and repair: implications for Fanconi anemia and breast cancer susceptibility. J. Biol. Chem. 2012;287(5):3366–80 doi: 10.1074/jbc.M111.311241 22167183

17. Saleh-Gohari N, Bryant HE, Schultz N, Parker KM, Cassel TN, Helleday T. Spontaneous homologous recombination is induced by collapsed replication forks that are caused by endogenous DNA single-strand breaks. Mol. Cell. Biol. 2005;25(16):7158–69 doi: 10.1128/MCB.25.16.7158-7169.2005 16055725

18. Sage JM, Gildemeister OS, Knight KL. Discovery of a novel function for human Rad51: maintenance of the mitochondrial genome. J. Biol. Chem. 2010;285(25):18984–90 doi: 10.1074/jbc.M109.099846 20413593

19. Meindl A, Hellebrand H, Wiek C, Erven V, Wappenschmidt B, Niederacher D, et al. Germline mutations in breast and ovarian cancer pedigrees establish RAD51C as a human cancer susceptibility gene. Nat. Genet. 2010;42(5):410–4 doi: 10.1038/ng.569 20400964

20. Vuorela M, Pylkas K, Hartikainen JM, Sundfeldt K, Lindblom A, von Wachenfeldt WA, et al. Further evidence for the contribution of the RAD51C gene in hereditary breast and ovarian cancer susceptibility. Breast Cancer Res.Treat. 2011;130(3):1003–10. doi: 10.1007/s10549-011-1677-x 21750962

21. De Leeneer K, Van Bockstal M, De Brouwer S, Swietek N, Schietecatte P, Sabbaghian N, et al. Evaluation of RAD51C as cancer susceptibility gene in a large breast-ovarian cancer patient population referred for genetic testing. Breast Cancer Res. Treat. 2012;133(1):393–8 doi: 10.1007/s10549-012-1998-4 22370629

22. Hasselbach L, Haase S, Fischer D, Kolberg HC, Sturzbecher HW. Characterisation of the promoter region of the human DNA-repair gene Rad51. Eur. J Gynaecol. Oncol. 2005;26(6):589–98. 16398215

23. Nowacka-Zawisza M, Wiśnik E, Wasilewski A, Skowrońska M, Forma E, Bryś M, et al. Polymorphisms of Homologous Recombination RAD51, RAD51B, XRCC2, and XRCC3 Genes and the Risk of Prostate Cancer. Anal. Cell. Pathol. 2015;2015:1–9

24. Zhao M, Chen P, Dong Y, Zhu X, Zhang X. Relationship between Rad51 G135C and G172T Variants and the Susceptibility to Cancer: A Meta-Analysis Involving 54 Case-Control Studies. He B, editor. PLoS One 2014;9(1):e87259 doi: 10.1371/journal.pone.0087259 24475258

25. Michalska MM, Samulak D, Romanowicz H, Smolarz B. Single Nucleotide Polymorphisms (SNPs) of RAD51-G172T and XRCC2-41657C/T Homologous Recombination Repair Genes and the Risk of Triple- Negative Breast Cancer in Polish Women. Pathol. Oncol. Res. 2015;21(4):935–40 doi: 10.1007/s12253-015-9922-y 25743260

26. Al-Zoubi MS, Mazzanti CM, Zavaglia K, Al Hamad M, Armogida I, Lisanti MP, et al. Homozygous T172T and Heterozygous G135C Variants of Homologous Recombination Repairing Protein RAD51 are Related to Sporadic Breast Cancer Susceptibility. Biochem. Genet. 2016;54(1):83–94 doi: 10.1007/s10528-015-9703-z 26650628

27. Sassi A, Popielarski M, Synowiec E, Morawiec Z, Wozniak K. BLM and RAD51 genes polymorphism and susceptibility to breast cancer. Pathol. Oncol. Res. 2013;19(3):451–9 doi: 10.1007/s12253-013-9602-8 23404160

28. Tulbah S, Alabdulkarim H, Alanazi M, Parine NR, Shaik J, Pathan AAK, et al. Polymorphisms in RAD51 and their relation with breast cancer in Saudi females. Onco. Targets. Ther. 2016;9:269–77 doi: 10.2147/OTT.S93343 26834486

29. Chai F, Liang Y, Chen L, Zhang F, Jiang J. Association between XRCC3 Thr241Met Polymorphism and Risk of Breast Cancer: Meta-Analysis of 23 Case-Control Studies. Med. Sci. Monit. 2015;21:3231–40 doi: 10.12659/MSM.894637 26498491

30. Mao C-F, Qian W-Y, Wu J-Z, Sun D-W, Tang J-H. Association between the XRCC3 Thr241Met polymorphism and breast cancer risk: an updated meta-analysis of 36 case-control studies. Asian Pac. J. Cancer Prev. 2014;15(16):6613–8 doi: 10.7314/apjcp.2014.15.16.6613 25169497

31. He X-F, Wei W, Su J, Yang Z-X, Liu Y, Zhang Y, et al. Association between the XRCC3 polymorphisms and breast cancer risk: meta-analysis based on case–control studies. Mol. Biol. Rep. 2012;39(5):5125–34 doi: 10.1007/s11033-011-1308-y 22161248

32. Smolarz B, Makowska M, Samulak D, Michalska MM, Mojs E, Wilczak M, et al. 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. 2015;15(2):151–7 doi: 10.1007/s10238-014-0284-7 24728564

33. Romanowicz H, Pyziak Ł, Jabłoński F, Bryś M, Forma E, Smolarz B. Analysis of DNA Repair Genes Polymorphisms in Breast Cancer. Pathol. Oncol. Res. 2017;23(1):117–23 doi: 10.1007/s12253-016-0110-5 27571987

34. Zheng Y, Zhang J, Hope K, Niu Q, Huo D, Olopade OI. Screening RAD51C nucleotide alterations in patients with a family history of breast and ovarian cancer. Breast Cancer Res.Treat. 2010;124(3):857–61 doi: 10.1007/s10549-010-1095-5 20697805

35. Akbari MR, Tonin P, Foulkes WD, Ghadirian P, Tischkowitz M, Narod SA. RAD51C germline mutations in breast and ovarian cancer patients. Breast Cancer Res. 2010;12(4):404 doi: 10.1186/bcr2619 20723205

36. Wong MW, Nordfors C, Mossman D, Pecenpetelovska G, Avery-Kiejda KA, Talseth-Palmer B, et al. BRIP1, PALB2, and RAD51C mutation analysis reveals their relative importance as genetic susceptibility factors for breast cancer. Breast Cancer Res.Treat. 2011;127(3):853–9 doi: 10.1007/s10549-011-1443-0 21409391

37. Pang Z, Yao L, Zhang J, Ouyang T, Li J, Wang T, et al. RAD51C germline mutations in Chinese women with familial breast cancer. Breast Cancer Res.Treat. 2011;129(3):1019–20 doi: 10.1007/s10549-011-1574-3 21597919

38. Clague J, Wilhoite G, Adamson A, Bailis A, Weitzel JN, Neuhausen SL. RAD51C germline mutations in breast and ovarian cancer cases from high-risk families. PLoS.One. 2011;6(9):e25632 doi: 10.1371/journal.pone.0025632 21980511

39. Gresner P, Gromadzinska J, Jablonska E, Stepnik M, Zambrano Quispe O, Twardowska E, et al. Single nucleotide polymorphisms in noncoding regions of Rad51C do not change the risk of unselected breast cancer but they modulate the level of oxidative stress and the DNA damage characteristics: a case-control study. Woloschak GE, editor. PLoS One 2014;9(10):e110696 doi: 10.1371/journal.pone.0110696 25343521

40. Moore JH, Gilbert JC, Tsai CT, Chiang FT, Holden T, Barney N, et al. A flexible computational framework for detecting, characterizing, and interpreting statistical patterns of epistasis in genetic studies of human disease susceptibility. J. Theor. Biol. 2006;241(2):252–61 doi: 10.1016/j.jtbi.2005.11.036 16457852

41. Pomerleau CS, Pomerleau OF, Snedecor SM, Mehringer AM. Defining a never-smoker: results from the nonsmokers survey. Addict.Behav. 2004;29(6):1149–54 doi: 10.1016/j.addbeh.2004.03.008 15236816

42. Sherry ST, Ward MH, Kholodov M, Baker J, Phan L, Smigielski EM, et al. dbSNP: the NCBI database of genetic variation. Nucleic Acids Res. 2001;29(1):308–11 doi: 10.1093/nar/29.1.308 11125122

43. Vorontsov IE, Kulakovskiy I V., Khimulya G, Nikolaeva DD, Makeev VJ. PERFECTOS-APE: Predicting regulatory functional effect of SNPs by approximate P-value estimation. Bioinforma. 2015—6th Int. Conf. Bioinforma. Model. Methods Algorithms, Proceedings; Part 8th Int. Jt. Conf. Biomed. Eng. Syst. Technol. BIOSTEC 2015 2015;102–8

44. Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, et al. A method and server for predicting damaging missense mutations. Nat. Methods. 2010. p. 248–9 doi: 10.1038/nmeth0410-248 20354512

45. The UniProt Consortium. UniProt: a worldwide hub of protein knowledge. Nucleic Acids Res. 2019;47(D1):D506–15 doi: 10.1093/nar/gky1049 30395287

46. Gresner P, Gromadzinska J, Polanska K, Twardowska E, Jurewicz J, Wasowicz W. Genetic variability of Xrcc3 and Rad51 modulates the risk of head and neck cancer. Gene. 2012;504(2):166–74 doi: 10.1016/j.gene.2012.05.030 22613844

47. Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 2005;21(2):263–5 doi: 10.1093/bioinformatics/bth457 15297300

48. Lewontin RC. The detection of linkage disequilibrium in molecular sequence data. Genetics. 1995;140(1):377–88 7635301

49. Gabriel SB, Schaffner SF, Nguyen H, Moore JM, Roy J, Blumenstiel B, et al. The structure of haplotype blocks in the human genome. Science. 2002;296(5576):2225–9 doi: 10.1126/science.1069424 12029063

50. Breiman L. Random Forests. Mach. Learn. 2001;45:5–32

51. Ishwaran H, Kogalur U. Fast Unified Random Forests for Survival, Regression, and Classification (RF-SRC). R package version 2.9.2. 2019

52. Hankin RKS. Package “permutations” R package version 1.0.5 2017

53. Li J, Malley JD, Andrew AS, Karagas MR, Moore JH, Hirschhorn J, et al. Detecting gene-gene interactions using a permutation-based random forest method. BioData Mining; 2016;9(1):14

54. Calle ML, Urrea V, Malats N, Van Steen K. mbmdr: an R package for exploring gene–gene interactions associated with binary or quantitative traits. Bioinformatics 2010;26(17):2198–9. doi: 10.1093/bioinformatics/btq352 20595460

55. Smolarz B, Zadrożny M, Duda-Szymańska J, Makowska M, Samulak D, Michalska MM, et al. RAD51 genotype and triple-negative breast cancer (TNBC) risk in Polish women. Pol. J. Pathol. 2013;64(1):39–43 doi: 10.5114/pjp.2013.34602 23625599

56. Lu J, Wang L-E, Xiong P, Sturgis EM, Spitz MR, Wei Q. 172G>T variant in the 5’ untranslated region of DNA repair gene RAD51 reduces risk of squamous cell carcinoma of the head and neck and interacts with a P53 codon 72 variant. Carcinogenesis 2007;28(5):988–94 doi: 10.1093/carcin/bgl225 17118968

57. Flygare J, Falt S, Ottervald J, Castro J, Dackland AL, Hellgren D, et al. Effects of HsRad51 overexpression on cell proliferation, cell cycle progression, and apoptosis. Exp.Cell Res. 2001;268(1):61–9 doi: 10.1006/excr.2001.5265 11461118

58. Yoo S, McKee BD. Overexpression of Drosophila Rad51 protein (DmRad51) disrupts cell cycle progression and leads to apoptosis. Chromosoma. 2004;113(2):92–101 doi: 10.1007/s00412-004-0300-x 15257466

59. Kurumizaka H, Enomoto R, Nakada M, Eda K, Yokoyama S, Shibata T. Region and amino acid residues required for Rad51C binding in the human Xrcc3 protein. Nucleic Acids Res. 2003;31(14):4041–50 doi: 10.1093/nar/gkg442 12853621

60. Liu J-C, Tsai C-W, Hsu C-M, Chang W-S, Li C-Y, Liu S-P, et al. Contribution of double strand break repair gene XRCC3 genotypes to nasopharyngeal carcinoma risk in Taiwan. Chin. J. Physiol. 2015;58(1):64–71 doi: 10.4077/CJP.2015.BAD279 25687493

61. Chen H-J, Chang W-S, Hsia T-C, Miao C-E, Chen W-C, Liang S-J, et al. Contribution of Genotype of DNA Double-strand Break Repair Gene XRCC3, Gender, and Smoking Behavior to Lung Cancer Risk in Taiwan. Anticancer Res. 2015;35(7):3893–9 26124335

62. Chang W-S, Tsai C-W, Wang J-Y, Ying T-H, Hsiao T-S, Chuang C-L, et al. Contribution of X-Ray Repair Complementing Defective Repair in Chinese Hamster Cells 3 (XRCC3) Genotype to Leiomyoma Risk. Anticancer Res. 2015;35(9):4691–6 26254358

63. Su C-H, Chang W-S, Hu P-S, Hsiao C-L, Ji H-X, Liao C-H, et al. Contribution of DNA Double-strand Break Repair Gene XRCC3 Genotypes to Triple-negative Breast Cancer Risk. Cancer Genomics Proteomics 2015;12(6):359–67 26543082

64. He X-F, Wei W, Li J-L, Shen X-L, Ding D, Wang S-L, et al. Association between the XRCC3 T241M polymorphism and risk of cancer: Evidence from 157 case–control studies. Gene 2013;523(1):10–9 doi: 10.1016/j.gene.2013.03.071 23562721

65. Rollinson S, Smith AG, Allan JM, Adamson PJ, Scott K, Skibola CF, et al. RAD51 homologous recombination repair gene haplotypes and risk of acute myeloid leukaemia. Leuk. Res. 2007;31(2):169–74 doi: 10.1016/j.leukres.2006.05.028 16890287

66. Spitz MR, Amos CI, D’Amelio A, Dong Q, Etzel C, Etzel C. Re: Discriminatory accuracy from single-nucleotide polymorphisms in models to predict breast cancer risk. J. Natl. Cancer Inst. 2009;101(24):1731–2 doi: 10.1093/jnci/djp394 19903803

67. Moore JH, Williams SM. Epistasis and Its Implications for Personal Genetics. Am. J. Hum. Genet. 2009;85(3):309–20 doi: 10.1016/j.ajhg.2009.08.006 19733727

68. Jiang R, Tang W, Wu X, Fu W. A random forest approach to the detection of epistatic interactions in case-control studies. BMC Bioinformatics 2009;10 Suppl 1:S65

69. Kulakovskiy I V., Vorontsov IE, Yevshin IS, Sharipov RN, Fedorova AD, Rumynskiy EI, et al. HOCOMOCO: Towards a complete collection of transcription factor binding models for human and mouse via large-scale ChIP-Seq analysis. Nucleic Acids Res. 2018;46(D1):D252–9 doi: 10.1093/nar/gkx1106 29140464