Association Between the NBS1 E185Q Polymorphism and Cancer Risk: a Meta-analysis

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2009 Apr 28

PMID 19393077

Citations 20

Authors

Meixia Lu

Jiachun Lu

Xiaobo Yang

Miao Yang

Hao Tan

Bai Yun

Luyuan Shi

Affiliations

Soon will be listed here.

Abstract

Background: NBS1 is a key DNA repair protein in the homologous recombination repair pathway and a signal modifier in the intra-S phase checkpoint that plays important roles in maintaining genomic stability. The NBS1 8360G>C (Glu185Gln) is one of the most commonly studied polymorphisms of the gene for their association with risk of cancers, but the results are conflicting.

Methods: We performed a meta-analysis using 16 eligible case-control studies (including 17 data sets) with a total of 9,734 patients and 10,325 controls to summarize the data on the association between the NBS1 8360G>C (E185Q) polymorphism and cancer risk.

Results: Compared with the common 8360GG genotype, the carriers of variant genotypes (i.e., 8360 GC/CC) had a 1.06-fold elevated risk of cancer (95% CI = 1.00-1.12, P = 0.05) in a dominant genetic model as estimated in a fixed effect model. However, the association was not found in an additive genetic model (CC vs GG) (odds ratio, OR = 0.98, 95% CI = 0.85-1.13, P = 0.78) nor in a recessive genetic model (CC vs GC +GG) (OR = 0.94, 95% CI = 0.82-1.07, P = 0.36). The effect of the 8360G>C (E185Q) polymorphism was further evaluated in stratification analysis. It was demonstrated that the increased risk of cancer associated with 8360G>C variant genotypes was more pronounced in the Caucasians (OR = 1.07, 95% CI = 1.01-1.14, P = 0.03).

Conclusion: Our meta-analysis suggests that the NBS1 E185Q variant genotypes (8360 GC/CC) might be associated with an increased risk of cancer, especially in Caucasians.

Citing Articles

Untangling the clinicopathological significance of MRE11-RAD50-NBS1 complex in sporadic breast cancers.

Alblihy A, Shoqafi A, Toss M, Algethami M, Harris A, Jeyapalan J NPJ Breast Cancer. 2021; 7(1):143.

PMID: 34782604 PMC: 8593132. DOI: 10.1038/s41523-021-00350-5.

Micronuclei Formation upon Radioiodine Therapy for Well-Differentiated Thyroid Cancer: The Influence of DNA Repair Genes Variants.

S Santos L, M Gil O, Silva S, Gomes B, Ferreira T, Limbert E Genes (Basel). 2020; 11(9).

PMID: 32957448 PMC: 7565468. DOI: 10.3390/genes11091083.

Association of Single-Nucleotide Polymorphisms in Monoubiquitinated FANCD2-DNA Damage Repair Pathway Genes With Breast Cancer in the Chinese Population.

Chen F, Wang H, Li H, Hu X, Dai X, Wang S Technol Cancer Res Treat. 2019; 17:1533033818819841.

PMID: 30799775 PMC: 6311543. DOI: 10.1177/1533033818819841.

Homologous Recombination Repair Polymorphisms and the Risk for Osteosarcoma.

Goricar K, Kovac V, Jazbec J, Lamovec J, Dolzan V J Med Biochem. 2017; 34(2):200-206.

PMID: 28356832 PMC: 4922323. DOI: 10.2478/jomb-2014-0031.

Association of the nibrin gene () variants with breast cancer.

Uzunoglu H, Korak T, Ergul E, Uren N, Sazci A, Utkan N Biomed Rep. 2016; 4(3):369-373.

PMID: 26998278 PMC: 4774354. DOI: 10.3892/br.2016.579.

References

Matsuura S, Kobayashi J, Tauchi H, Komatsu K . Nijmegen breakage syndrome and DNA double strand break repair by NBS1 complex. Adv Biophys. 2004; 38:65-80. View

Buslov K, Iyevleva A, Chekmariova E, Suspitsin E, Togo A, Kuligina E . NBS1 657del5 mutation may contribute only to a limited fraction of breast cancer cases in Russia. Int J Cancer. 2004; 114(4):585-9. DOI: 10.1002/ijc.20765. View

Allen-Brady K, Camp N . Characterization of the linkage disequilibrium structure and identification of tagging-SNPs in five DNA repair genes. BMC Cancer. 2005; 5:99. PMC: 1208870. DOI: 10.1186/1471-2407-5-99. View

Howlett N, Scuric Z, DAndrea A, Schiestl R . Impaired DNA double strand break repair in cells from Nijmegen breakage syndrome patients. DNA Repair (Amst). 2005; 5(2):251-7. DOI: 10.1016/j.dnarep.2005.10.004. View

Cerosaletti K, Morrison V, Sabath D, Willerford D, Concannon P . Mutations and molecular variants of the NBS1 gene in non-Hodgkin lymphoma. Genes Chromosomes Cancer. 2002; 35(3):282-6. DOI: 10.1002/gcc.10114. View

Nyholt D . ssSNPer: identifying statistically similar SNPs to aid interpretation of genetic association studies. Bioinformatics. 2006; 22(23):2960-1. DOI: 10.1093/bioinformatics/btl518. View

. Nijmegen breakage syndrome. The International Nijmegen Breakage Syndrome Study Group. Arch Dis Child. 2000; 82(5):400-6. PMC: 1718318. DOI: 10.1136/adc.82.5.400. View

Wang Y, Cortez D, Yazdi P, NEFF N, Elledge S, Qin J . BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures. Genes Dev. 2000; 14(8):927-39. PMC: 316544. View

Steineck G, Wiholm B, Gerhardsson de Verdier M . Acetaminophen, some other drugs, some diseases and the risk of transitional cell carcinoma. A population-based case-control study. Acta Oncol. 1995; 34(6):741-8. DOI: 10.3109/02841869509127181. View

10.

Thirumaran R, Lorenzo Bermejo J, Rudnai P, Gurzau E, Koppova K, Goessler W . Single nucleotide polymorphisms in DNA repair genes and basal cell carcinoma of skin. Carcinogenesis. 2006; 27(8):1676-81. DOI: 10.1093/carcin/bgi381. View

11.

Digweed M, Sperling K . Nijmegen breakage syndrome: clinical manifestation of defective response to DNA double-strand breaks. DNA Repair (Amst). 2004; 3(8-9):1207-17. DOI: 10.1016/j.dnarep.2004.03.004. View

12.

Forget A, Bennett B, Knight K . Xrcc3 is recruited to DNA double strand breaks early and independent of Rad51. J Cell Biochem. 2004; 93(3):429-36. DOI: 10.1002/jcb.20232. View

13.

Lau J, Ioannidis J, Schmid C . Quantitative synthesis in systematic reviews. Ann Intern Med. 1998; 127(9):820-6. DOI: 10.7326/0003-4819-127-9-199711010-00008. View

14.

Pardini B, Naccarati A, Novotny J, Smerhovsky Z, Vodickova L, Polakova V . DNA repair genetic polymorphisms and risk of colorectal cancer in the Czech Republic. Mutat Res. 2007; 638(1-2):146-53. DOI: 10.1016/j.mrfmmm.2007.09.008. View

15.

Millikan R, Player J, Decotret A, Tse C, Keku T . Polymorphisms in DNA repair genes, medical exposure to ionizing radiation, and breast cancer risk. Cancer Epidemiol Biomarkers Prev. 2005; 14(10):2326-34. DOI: 10.1158/1055-9965.EPI-05-0186. View

16.

Lu J, Wei Q, Bondy M, Li D, Brewster A, Shete S . Polymorphisms and haplotypes of the NBS1 gene are associated with risk of sporadic breast cancer in non-Hispanic white women <or=55 years. Carcinogenesis. 2006; 27(11):2209-16. DOI: 10.1093/carcin/bgl077. View

17.

Popanda O, Tan X, Ambrosone C, Kropp S, Helmbold I, von Fournier D . 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 Biomarkers Prev. 2006; 15(5):1048-50. DOI: 10.1158/1055-9965.EPI-06-0046. View

18.

Kobayashi J . Molecular mechanism of the recruitment of NBS1/hMRE11/hRAD50 complex to DNA double-strand breaks: NBS1 binds to gamma-H2AX through FHA/BRCT domain. J Radiat Res. 2005; 45(4):473-8. DOI: 10.1269/jrr.45.473. View

19.

Kuschel B, Auranen A, McBride S, Novik K, Antoniou A, Lipscombe J . Variants in DNA double-strand break repair genes and breast cancer susceptibility. Hum Mol Genet. 2002; 11(12):1399-407. DOI: 10.1093/hmg/11.12.1399. View

20.

Ziolkowska I, Mosor M, Wierzbicka M, Rydzanicz M, Pernak-Schwarz M, Nowak J . Increased risk of larynx cancer in heterozygous carriers of the I171V mutation of the NBS1 gene. Cancer Sci. 2007; 98(11):1701-5. PMC: 11158328. DOI: 10.1111/j.1349-7006.2007.00594.x. View