Evaluating genetic risk for prostate cancer among Japanese and Latinos

Iona Cheng, Gary K. Chen, Hidewaki Nakagawa, Jing He, Peggy Wan, Cathy C. Laurie, Jess Shen, Xin Sheng, Loreall C. Pooler, Andrew T. Crenshaw, Daniel B. Mirel, Atsushi Takahashi, Michiaki Kubo, Yusuke Nakamura, Ali Amin Al Olama, Sara Benlloch, Jenny L. Donovan, Michelle Guy, Freddie C. Hamdy, Zsofia Kote-JaraiDavid E. Neal, Lynne R. Wilkens, Kristine R. Monroe, Daniel O. Stram, Kenneth Muir, Rosalind A. Eeles, Douglas F. Easton, Laurence N. Kolonel, Brian E. Henderson, Loïc Le Marchand, Christopher A. Haiman

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Abstract

Background: There have been few genome-wide association studies (GWAS) of prostate cancer among diverse populations. To search for novel prostate cancer risk variants, we conducted GWAS of prostate cancer in Japanese and Latinos. In addition, we tested prostate cancer risk variants and developed genetic risk models of prostate cancer for Japanese and Latinos. Methods: Our first-stage GWAS of prostate cancer included Japanese (cases/controls = 1,033/1,042) and Latino (cases/controls = 1,043/1,057) from the Multiethnic Cohort (MEC). Significant associations from stage I (P < 1.0 × 10-4) were examined in silico in GWAS of prostate cancer (stage II) in Japanese (cases/controls = 1,583/3,386) and Europeans (cases/controls = 1,854/1,894). Results: No novel stage I single-nucleotide polymorphism (SNP) outside of known risk regions reached genome-wide significance. For Japanese, in stage I, the most notable putative novel association was seen with 10 SNPs (P ≤ 8.0 × 10-6) at chromosome 2q33; however, this was not replicated in stage II. For Latinos, the most significant association was observed with rs17023900 at the known 3p12 risk locus (stage I:OR = 1.45; P = 7.01 × 10-5 and stage II: OR = 1.58; P = 3.05 × 10-7). The majority of the established risk variants for prostate cancer, 79% and 88%, were positively associated with prostate cancer in Japanese and Latinos (stage I), respectively. The cumulative effects of these variants significantly influence prostate cancer risk (OR per allele = 1.10; P = 2.71 × 10-25 and OR = 1.07; P = 1.02 × 10-16 for Japanese and Latinos, respectively). Conclusion and Impact: Our GWAS of prostate cancer did not identify novel genome-wide significant variants. However, our findings show that established risk variants for prostate cancer significantly contribute to risk among Japanese and Latinos.

Original languageEnglish
Pages (from-to)2048-2058
Number of pages11
JournalCancer Epidemiology Biomarkers and Prevention
Volume21
Issue number11
DOIs
Publication statusPublished - 01-11-2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Epidemiology
  • Oncology

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    Cheng, I., Chen, G. K., Nakagawa, H., He, J., Wan, P., Laurie, C. C., Shen, J., Sheng, X., Pooler, L. C., Crenshaw, A. T., Mirel, D. B., Takahashi, A., Kubo, M., Nakamura, Y., Al Olama, A. A., Benlloch, S., Donovan, J. L., Guy, M., Hamdy, F. C., ... Haiman, C. A. (2012). Evaluating genetic risk for prostate cancer among Japanese and Latinos. Cancer Epidemiology Biomarkers and Prevention, 21(11), 2048-2058. https://doi.org/10.1158/1055-9965.EPI-12-0598