EphB2 SNPs and Sporadic Prostate Cancer Risk in African American Men

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2011 May 24

PMID 21603658

Citations 18

Authors

Christiane M Robbins

Stanley Hooker

Rick A Kittles

John D Carpten

Affiliations

Soon will be listed here.

Abstract

The EphB2 gene has been implicated as a tumor suppressor gene somatically altered in both prostate cancer (PC) and colorectal cancer. We have previously shown an association between an EphB2 germline nonsense variant and risk of familial prostate cancer among African American Men (AAM). Here we set out to test the hypothesis that common variation within the EphB2 locus is associated with increased risk of sporadic PC in AAM. We genotyped a set of 341 single nucleotide polymorphisms (SNPs) encompassing the EphB2 locus, including known and novel coding and noncoding variants, in 490 AA sporadic PC cases and 567 matched controls. Single marker-based logistical regression analyses revealed seven EphB2 SNPs showing statistically significant association with prostate cancer risk in our population. The most significant association was achieved for a novel synonymous coding SNP, TGen-624, (Odds Ratio (OR) = 0.22; 95% Confidence Interval (CI) 0.08-0.66, p = 1×10(-5)). Two other SNPs also show significant associations toward a protective effect rs10465543 and rs12090415 (p = 1×10(-4)), OR = 0.49 and 0.7, respectively. Two additional SNPs revealed trends towards an increase in risk of prostate cancer, rs4612601 and rs4263970 (p = 0.001), OR = 1.35 and 1.31, respectively. Furthermore, haplotype analysis revealed low levels of linkage disequilibrium within the region, with two blocks being associated with prostate cancer risk among our population. These data suggest that genetic variation at the EphB2 locus may increase risk of sporadic PC among AAM.

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References

Robbins C, Torres J, Hooker S, Bonilla C, Hernandez W, Candreva A . Confirmation study of prostate cancer risk variants at 8q24 in African Americans identifies a novel risk locus. Genome Res. 2007; 17(12):1717-22. PMC: 2099580. DOI: 10.1101/gr.6782707. View

Alazzouzi H, Davalos V, Kokko A, Domingo E, Woerner S, Wilson A . Mechanisms of inactivation of the receptor tyrosine kinase EPHB2 in colorectal tumors. Cancer Res. 2005; 65(22):10170-3. DOI: 10.1158/0008-5472.CAN-05-2580. View

Steinberg G, Carter B, Beaty T, Childs B, Walsh P . Family history and the risk of prostate cancer. Prostate. 1990; 17(4):337-47. DOI: 10.1002/pros.2990170409. View

Rennert H, Zeigler-Johnson C, Addya K, Finley M, Walker A, Spangler E . Association of susceptibility alleles in ELAC2/HPC2, RNASEL/HPC1, and MSR1 with prostate cancer severity in European American and African American men. Cancer Epidemiol Biomarkers Prev. 2005; 14(4):949-57. DOI: 10.1158/1055-9965.EPI-04-0637. View

Kupfer S, Torres J, Hooker S, Anderson J, Skol A, Ellis N . Novel single nucleotide polymorphism associations with colorectal cancer on chromosome 8q24 in African and European Americans. Carcinogenesis. 2009; 30(8):1353-7. PMC: 2718071. DOI: 10.1093/carcin/bgp123. View

Xu J, Kibel A, Hu J, Turner A, Pruett K, Zheng S . Prostate cancer risk associated loci in African Americans. Cancer Epidemiol Biomarkers Prev. 2009; 18(7):2145-9. PMC: 2729762. DOI: 10.1158/1055-9965.EPI-09-0091. View

Benford M, VanCleave T, Lavender N, Kittles R, Kidd L . 8q24 sequence variants in relation to prostate cancer risk among men of African descent: a case-control study. BMC Cancer. 2010; 10:334. PMC: 2912864. DOI: 10.1186/1471-2407-10-334. View

Kittles R, Baffoe-Bonnie A, Moses T, ROBBINS C, Ahaghotu C, Huusko P . A common nonsense mutation in EphB2 is associated with prostate cancer risk in African American men with a positive family history. J Med Genet. 2005; 43(6):507-11. PMC: 2564535. DOI: 10.1136/jmg.2005.035790. View

Jemal A, Siegel R, Xu J, Ward E . Cancer statistics, 2010. CA Cancer J Clin. 2010; 60(5):277-300. DOI: 10.3322/caac.20073. View

10.

Barrett J, Fry B, Maller J, Daly M . Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 2004; 21(2):263-5. DOI: 10.1093/bioinformatics/bth457. View

11.

Frazer K, Ballinger D, Cox D, Hinds D, Stuve L, Boudreau A . A second generation human haplotype map of over 3.1 million SNPs. Nature. 2007; 449(7164):851-61. PMC: 2689609. DOI: 10.1038/nature06258. View

12.

Freedman M, Haiman C, Patterson N, McDonald G, Tandon A, Waliszewska A . Admixture mapping identifies 8q24 as a prostate cancer risk locus in African-American men. Proc Natl Acad Sci U S A. 2006; 103(38):14068-73. PMC: 1599913. DOI: 10.1073/pnas.0605832103. View

13.

Kieffer N, Schmitz M, Scheiden R, Nathan M, Faber J . Involvement of the RNAse L gene in prostate cancer. Bull Soc Sci Med Grand Duche Luxemb. 2006; (1):21-8. View

14.

Huusko P, Ponciano-Jackson D, Wolf M, Kiefer J, Azorsa D, Tuzmen S . Nonsense-mediated decay microarray analysis identifies mutations of EPHB2 in human prostate cancer. Nat Genet. 2004; 36(9):979-83. DOI: 10.1038/ng1408. View

15.

Powell I, Bock C, Ruterbusch J, Sakr W . Evidence supports a faster growth rate and/or earlier transformation to clinically significant prostate cancer in black than in white American men, and influences racial progression and mortality disparity. J Urol. 2010; 183(5):1792-6. PMC: 3840791. DOI: 10.1016/j.juro.2010.01.015. View

16.

Oba S, Wang Y, Song J, Li Z, Kobayashi K, Tsugane S . Genomic structure and loss of heterozygosity of EPHB2 in colorectal cancer. Cancer Lett. 2001; 164(1):97-104. DOI: 10.1016/s0304-3835(00)00716-3. View

17.

Gann P . Risk factors for prostate cancer. Rev Urol. 2006; 4 Suppl 5:S3-S10. PMC: 1476014. View

18.

Bock C, Schwartz A, Ruterbusch J, Levin A, Neslund-Dudas C, Land S . Results from a prostate cancer admixture mapping study in African-American men. Hum Genet. 2009; 126(5):637-42. PMC: 2975267. DOI: 10.1007/s00439-009-0712-z. View

19.

Beuten J, Gelfond J, Franke J, Shook S, Johnson-Pais T, Thompson I . Single and multivariate associations of MSR1, ELAC2, and RNASEL with prostate cancer in an ethnic diverse cohort of men. Cancer Epidemiol Biomarkers Prev. 2010; 19(2):588-99. PMC: 5034730. DOI: 10.1158/1055-9965.EPI-09-0864. View

20.

Xu B, Tong N, Li J, Zhang Z, Wu H . ELAC2 polymorphisms and prostate cancer risk: a meta-analysis based on 18 case-control studies. Prostate Cancer Prostatic Dis. 2010; 13(3):270-7. PMC: 2922791. DOI: 10.1038/pcan.2010.6. View