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

Journal Article · Tue Nov 30 23:00:00 EST 2010 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/j.ijrobp.2010.07.036· OSTI ID:21491492

Kerns, Sarah L; Ostrer, Harry ^[1]; Stock, Richard ^[2]; Li, William ^[3]; Moore, Julian ^[2]; Pearlman, Alexander; Campbell, Christopher ^[1]; Yongzhao, Shao ^[4]; Stone, Nelson ^[2]; Kusnetz, Lynda ^[2]

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1. Department of Pediatrics, New York University School of Medicine, New York, NY (United States)
2. Department of Radiation Oncology, Mount Sinai School of Medicine, New York, NY (United States)
3. Department of Radiation Oncology, Queens/Elmhurst Hospital Center, Jamaica, NY (Jamaica)
4. Division of Biostatistics, New York University School of Medicine, New York, NY (United States)

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 x 10{sup -8}, Bonferroni p = 0.028). We identified four additional SNPs that tended toward a significant association with an unadjusted p value < 10{sup -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.

• OSTI ID: 21491492
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 5 Vol. 78; ISSN IOBPD3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
BODY
DISEASES
FSH
GENES
GLANDS
GONADOTROPINS
HORMONES
MALE GENITALS
MATHEMATICS
MEDICINE
MEMBRANE PROTEINS
MULTIVARIATE ANALYSIS
NEOPLASMS
NUCLEAR MEDICINE
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANS
PEPTIDE HORMONES
PITUITARY HORMONES
PROSTATE
PROTEINS
RADIOLOGY
RADIOTHERAPY
RECEPTORS
STATISTICS
THERAPY