Faculty Collaboration Database

Genome-wide association study to identify single nucleotide polymorphisms (SNPs) associated with the development of erectile dysfunction in African-American men after radiotherapy for prostate cancer. Int J Radiat Oncol Biol Phys 2010 Dec 01;78(5):1292-300

Date

10/12/2010

Pubmed ID

20932654

Pubmed Central ID

PMC2991431

DOI

10.1016/j.ijrobp.2010.07.036

Scopus ID

2-s2.0-78549233654 (requires institutional sign-in at Scopus site)   127 Citations

Abstract

PURPOSE: To identify single nucleotide polymorphisms (SNPs) associated with erectile dysfunction (ED) among African-American prostate cancer patients treated with external beam radiation therapy.

METHODS AND MATERIALS: A cohort of African-American prostate cancer patients treated with external beam radiation therapy was observed for the development of ED by use of the five-item Sexual Health Inventory for Men (SHIM) questionnaire. Final analysis included 27 cases (post-treatment SHIM score ≤7) and 52 control subjects (post-treatment SHIM score ≥16). A genome-wide association study was performed using approximately 909,000 SNPs genotyped on Affymetrix 6.0 arrays (Affymetrix, Santa Clara, CA).

RESULTS: We identified SNP rs2268363, located in the follicle-stimulating hormone receptor (FSHR) gene, as significantly associated with ED after correcting for multiple comparisons (unadjusted p = 5.46 × 10(-8), Bonferroni p = 0.028). We identified four additional SNPs that tended toward a significant association with an unadjusted p value < 10(-6). Inference of population substructure showed that cases had a higher proportion of African ancestry than control subjects (77% vs. 60%, p = 0.005). A multivariate logistic regression model that incorporated estimated ancestry and four of the top-ranked SNPs was a more accurate classifier of ED than a model that included only clinical variables.

CONCLUSIONS: To our knowledge, this is the first genome-wide association study to identify SNPs associated with adverse effects resulting from radiotherapy. It is important to note that the SNP that proved to be significantly associated with ED is located within a gene whose encoded product plays a role in male gonad development and function. Another key finding of this project is that the four SNPs most strongly associated with ED were specific to persons of African ancestry and would therefore not have been identified had a cohort of European ancestry been screened. This study demonstrates the feasibility of a genome-wide approach to investigate genetic predisposition to radiation injury.

Author List

Kerns SL, Ostrer H, Stock R, Li W, Moore J, Pearlman A, Campbell C, Shao Y, Stone N, Kusnetz L, Rosenstein BS

Author

Sarah L. Kerns PhD Associate Professor in the Radiation Oncology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aged
Case-Control Studies
Cohort Studies
Erectile Dysfunction
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide
Prostatic Neoplasms
Radiation Injuries
Receptors, FSH
Regression Analysis
Surveys and Questionnaires