DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in and Mutation Carriers

English version České info

Women harboring a germ-line mutation in the BRCA1 or BRCA2 genes have a high lifetime risk to develop breast and/or ovarian cancer. However, not all carriers develop cancer and high variability exists regarding age of onset of the disease and type of tumor. One of the causes of this variability lies in other genetic factors that modulate the phenotype, the so-called modifier genes. Identification of these genes might have important implications for risk assessment and decision making regarding prevention of the disease. Given that BRCA1 and BRCA2 participate in the repair of DNA double strand breaks, here we have investigated whether variations, Single Nucleotide Polymorphisms (SNPs), in genes participating in other DNA repair pathway may be associated with cancer risk in BRCA carriers. We have selected the Base Excision Repair pathway because BRCA defective cells are extremely sensitive to the inhibition of one of its components, PARP1. Thanks to a large international collaborative effort, we have been able to identify at least two SNPs that are associated with increased cancer risk in BRCA1 and BRCA2 mutation carriers respectively. These findings could have implications not only for risk assessment, but also for treatment of BRCA1/2 mutation carriers with PARP inhibitors.

Vyšlo v časopise: DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in and Mutation Carriers. PLoS Genet 10(4): e32767. doi:10.1371/journal.pgen.1004256
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004256

Souhrn

Zdroje

1. AntoniouA, PharoahPD, NarodS, RischHA, EyfjordJE, et al. (2003) Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet 72 : 1117–1130.

2. ChenS, IversenES, FriebelT, FinkelsteinD, WeberBL, et al. (2006) Characterization of BRCA1 and BRCA2 mutations in a large United States sample. J Clin Oncol 24 : 863–871.

3. MilneRL, OsorioA, CajalTR, VegaA, LlortG, et al. (2008) The average cumulative risks of breast and ovarian cancer for carriers of mutations in BRCA1 and BRCA2 attending genetic counseling units in Spain. Clin Cancer Res 14 : 2861–2869.

4. Chenevix-TrenchG, MilneRL, AntoniouAC, CouchFJ, EastonDF, et al. (2007) An international initiative to identify genetic modifiers of cancer risk in BRCA1 and BRCA2 mutation carriers: the Consortium of Investigators of Modifiers of BRCA1 and BRCA2 (CIMBA). Breast Cancer Res 9 : 104.

5. AntoniouAC, KuchenbaeckerKB, SoucyP, BeesleyJ, ChenX, et al. (2012) Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. Breast Cancer Res 14: R33.

6. AntoniouAC, SpurdleAB, SinilnikovaOM, HealeyS, PooleyKA, et al. (2008) Common breast cancer-predisposition alleles are associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers. Am J Hum Genet 82 : 937–948.

7. AntoniouAC, SinilnikovaOM, McGuffogL, HealeyS, NevanlinnaH, et al. (2009) Common variants in LSP1, 2q35 and 8q24 and breast cancer risk for BRCA1 and BRCA2 mutation carriers. Hum Mol Genet 18 : 4442–4456.

8. AntoniouAC, WangX, FredericksenZS, McGuffogL, TarrellR, et al. (2010) A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population. Nat Genet 42 : 885–892.

9. AntoniouAC, SinilnikovaOM, SimardJ, LeoneM, DumontM, et al. (2007) RAD51 135G→C modifies breast cancer risk among BRCA2 mutation carriers: results from a combined analysis of 19 studies. Am J Hum Genet 81 : 1186–1200.

10. MoynahanME, ChiuJW, KollerBH, JasinM (1999) Brca1 controls homology-directed DNA repair. Mol Cell 4 : 511–518.

11. PatelKJ, YuVP, LeeH, CorcoranA, ThistlethwaiteFC, et al. (1998) Involvement of Brca2 in DNA repair. Mol Cell 1 : 347–357.

12. XuG, HerzigM, RotreklV, WalterCA (2008) Base excision repair, aging and health span. Mech Ageing Dev 129 : 366–382.

13. FarmerH, McCabeN, LordCJ, TuttAN, JohnsonDA, et al. (2005) Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 434 : 917–921.

14. OsorioA, MilneRL, AlonsoR, PitaG, PeterlongoP, et al. (2011) Evaluation of the XRCC1 gene as a phenotypic modifier in BRCA1/2 mutation carriers. Results from the consortium of investigators of modifiers of BRCA1/BRCA2. Br J Cancer 104 : 1356–1361.

15. ZhangY, NewcombPA, EganKM, Titus-ErnstoffL, ChanockS, et al. (2006) Genetic polymorphisms in base-excision repair pathway genes and risk of breast cancer. Cancer Epidemiol Biomarkers Prev 15 : 353–358.

16. ZipprichA, KussO, RogowskiS, KleberG, LottererE, et al. (2010) Incorporating indocyanin green clearance into the Model for End Stage Liver Disease (MELD-ICG) improves prognostic accuracy in intermediate to advanced cirrhosis. Gut 59 : 963–968.

17. PopandaO, SeiboldP, NikolovI, OakesCC, BurwinkelB, et al. (2013) Germline variants of base excision repair genes and breast cancer: A polymorphism in DNA polymerase gamma modifies gene expression and breast cancer risk. Int J Cancer 132 : 55–62.

18. RobertsMR, ShieldsPG, AmbrosoneCB, NieJ, MarianC, et al. (2011) Single-nucleotide polymorphisms in DNA repair genes and association with breast cancer risk in the web study. Carcinogenesis 32 : 1223–1230.

19. SangrajrangS, SchmezerP, BurkholderI, WaasP, BoffettaP, et al. (2008) Polymorphisms in three base excision repair genes and breast cancer risk in Thai women. Breast Cancer Res Treat 111 : 279–288.

20. Ming-ShieanH, YuJC, WangHW, ChenST, HsiungCN, et al. (2010) Synergistic effects of polymorphisms in DNA repair genes and endogenous estrogen exposure on female breast cancer risk. Ann Surg Oncol 17 : 760–771.

21. ZipprichJ, TerryMB, Brandt-RaufP, FreyerGA, LiaoY, 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.

22. BanerjeeD, MandalSM, DasA, HegdeML, DasS, et al. (2011) Preferential repair of oxidized base damage in the transcribed genes of mammalian cells. J Biol Chem 286 : 6006–6016.

23. WeiH, KamatA, ChenM, KeHL, ChangDW, et al. (2012) Association of polymorphisms in oxidative stress genes with clinical outcomes for bladder cancer treated with Bacillus Calmette-Guerin. PLoS One 7: e38533.

24. KinslowCJ, El-ZeinRA, RondelliCM, HillCE, WickliffeJK, et al. (2010) Regulatory regions responsive to oxidative stress in the promoter of the human DNA glycosylase gene NEIL2. Mutagenesis 25 : 171–177.

25. KinslowCJ, El-ZeinRA, HillCE, WickliffeJK, Abdel-RahmanSZ (2008) Single nucleotide polymorphisms 5′ upstream the coding region of the NEIL2 gene influence gene transcription levels and alter levels of genetic damage. Genes Chromosomes Cancer 47 : 923–932.

26. DeyS, MaitiAK, HegdeML, HegdePM, BoldoghI, et al. (2012) Increased risk of lung cancer associated with a functionally impaired polymorphic variant of the human DNA glycosylase NEIL2. DNA Repair (Amst) 11 : 570–578.

27. ZhaiX, ZhaoH, LiuZ, WangLE, El-NaggarAK, et al. (2008) Functional variants of the NEIL1 and NEIL2 genes and risk and progression of squamous cell carcinoma of the oral cavity and oropharynx. Clin Cancer Res 14 : 4345–4352.

28. ArcandSL, ProvencherD, Mes-MassonAM, ToninPN (2005) OGG1 Cys326 variant, allelic imbalance of chromosome band 3p25.3 and TP53 mutations in ovarian cancer. Int J Oncol 27 : 1315–1320.

29. RossnerPJr, TerryMB, GammonMD, ZhangFF, TeitelbaumSL, et al. (2006) OGG1 polymorphisms and breast cancer risk. Cancer Epidemiol Biomarkers Prev 15 : 811–815.

30. WeiW, HeXF, QinJB, SuJ, LiSX, et al. (2012) Association between the OGG1 Ser326Cys and APEX1 Asp148Glu polymorphisms and lung cancer risk: a meta-analysis. Mol Biol Rep 39 : 11249–11262.

31. XieY, YangH, MillerJH, ShihDM, HicksGG, et al. (2008) Cells deficient in oxidative DNA damage repair genes Myh and Ogg1 are sensitive to oxidants with increased G2/M arrest and multinucleation. Carcinogenesis 29 : 722–728.

32. CouchFJ, WangX, McGuffogL, LeeA, OlswoldC, et al. (2013) Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk. PLoS Genet 9: e1003212.

33. VisnesT, AkbariM, HagenL, SlupphaugG, KrokanHE (2008) The rate of base excision repair of uracil is controlled by the initiating glycosylase. DNA Repair (Amst) 7 : 1869–1881.

34. AntoniouAC, GoldgarDE, AndrieuN, Chang-ClaudeJ, BrohetR, et al. (2005) A weighted cohort approach for analysing factors modifying disease risks in carriers of high-risk susceptibility genes. Genet Epidemiol 29 : 1–11.

35. GaudetMM, KuchenbaeckerKB, VijaiJ, KleinRJ, KirchhoffT, et al. (2013) Identification of a BRCA2-Specific Modifier Locus at 6p24 Related to Breast Cancer Risk. PLoS Genet 9: e1003173.

36. BarnesDR, LeeA, EastonDF, AntoniouAC (2012) Evaluation of association methods for analysing modifiers of disease risk in carriers of high-risk mutations. Genet Epidemiol 36 : 274–291.

37. BarnesDR, AntoniouAC (2012) Unravelling modifiers of breast and ovarian cancer risk for BRCA1 and BRCA2 mutation carriers: update on genetic modifiers. J Intern Med 271 : 331–343.

38. AminN, van DuijnCM, AulchenkoYS (2007) A genomic background based method for association analysis in related individuals. PLoS One 2: e1274.

39. LeuteneggerAL, PrumB, GeninE, VernyC, LemainqueA, et al. (2003) Estimation of the inbreeding coefficient through use of genomic data. Am J Hum Genet 73 : 516–523.

40. DelaneauO, ZaguryJF (2012) Haplotype inference. Methods Mol Biol 888 : 177–196.

41. HowieBN, DonnellyP, MarchiniJ (2009) A flexible and accurate genotype imputation method for the next generation of genome-wide association studies. PLoS Genet 5: e1000529.

42. PruimRJ, WelchRP, SannaS, TeslovichTM, ChinesPS, et al. (2010) LocusZoom: regional visualization of genome-wide association scan results. Bioinformatics 26 : 2336–2337.