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Basic Research

Genetic variation in IL-16 miRNA target site and time to prostate cancer diagnosis in African-American men

Prostate Cancer and Prostatic Diseases volume 16, pages 308–314 (2013)Cite this article

Subjects

Abstract

BACKGROUND:

Men with a family history of prostate cancer and African-American men are at high risk for prostate cancer and in need of personalized risk estimates to inform screening decisions. This study evaluated genetic variants in genes encoding microRNA (miRNA) binding sites for informing of time to prostate cancer diagnosis among ethnically diverse, high-risk men undergoing prostate cancer screening.

METHODS:

The Prostate Cancer Risk Assessment Program (PRAP) is a longitudinal screening program for high-risk men. The eligibility includes men aged between 35 and 69 years with a family history of prostate cancer or African descent. Participants with ⩾1 follow-up visit were included in the analyses (n=477). Genetic variants in genes encoding miRNA binding sites (ALOX15 (arachidonate 15-lipooxygenase), IL-16, IL-18 and RAF1 (v-raf-1 murine leukemia viral oncogene homolog 1)) previously implicated in prostate cancer development were evaluated. Genotyping methods included Taqman SNP Genotyping Assay or pyrosequencing. Cox models were used to assess time to prostate cancer diagnosis by risk genotype.

RESULTS:

Among 256 African Americans with ⩾one follow-up visit, the TT genotype at rs1131445 in IL-16 was significantly associated with earlier time to prostate cancer diagnosis vs the CC/CT genotypes (P=0.013), with a suggestive association after correction for false discovery (P=0.065). Hazard ratio after controlling for age and PSA for TT vs CC/CT among African Americans was 3.0 (95% confidence interval: 1.26–7.12). No association with time to diagnosis was detected among Caucasians by IL-16 genotype. No association with time to prostate cancer diagnosis was found for the other miRNA target genotypes.

CONCLUSIONS:

Genetic variation in IL-16 encoding miRNA target site may be informative of time to prostate cancer diagnosis among African-American men enrolled in prostate cancer risk assessment, which may inform individualized prostate cancer screening strategies in the future.

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Acknowledgements

We are grateful to the participants of the PRAP; Keystone Grant for Personalized Risk and Prevention (Grant number 72002-10, Fox Chase Cancer Center Institutional Funds) (VNG); VNG is supported by the Department of Defense Physician Research Training Award (W81XWH-09-1-0302) (VNG); and P30 CA006927 from the National Cancer Institute (Cancer Center Support Grant). PRAP has been supported by Pennsylvania Department of Health Grants (98-PADOH-ME-98155) and (No. 4100042732).

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Authors and Affiliations

  1. Cancer Prevention and Control Program, Fox Chase Cancer Center, Philadelphia, PA, USA

    L Hughes, K Ruth & V N Giri

  2. Department of Biostatistics, Fox Chase Cancer Center, Philadelphia, PA, USA

    K Ruth

  3. Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, USA

    T R Rebbeck

  4. Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA, USA

    V N Giri

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Correspondence to V N Giri.

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Hughes, L., Ruth, K., Rebbeck, T. et al. Genetic variation in IL-16 miRNA target site and time to prostate cancer diagnosis in African-American men. Prostate Cancer Prostatic Dis 16, 308–314 (2013). https://doi.org/10.1038/pcan.2013.36

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