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Purpose-To identify single nucleotide polymorphisms (SNPs) associated with erectile dysfunction (ED) among African American prostate cancer patients treated with external beam radiation therapy (EBRT).Methods and Materials-A cohort of African American prostate cancer patients treated with EBRT was followed for development of ED using the five-item Sexual Health Inventory for Men (SHIM) questionnaire. Final analysis included 27 cases (post-treatment SHIM score ≤ 7) and 52 controls (post-treatment SHIM score ≥ 16). A genome-wide association study was performed using ∼909,000 SNPs genotyped on Affymetrix 6.0 arrays.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-value = 5.46×10 −8 ; Bonferroni p-value = 0.028). We identified four additional Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptInt J Radiat Oncol Biol Phys. Author manuscript; available in PMC 2011 December 1. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptSNPs that tended toward significant association with unadjusted p-value < 10 −06 . Inference of population substructure revealed that cases had a higher proportion of African ancestry compared to controls (77% compared to 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 the best of 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 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 people 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.

The European Randomized Study of Screening for Prostate (ERSPC) has updated their previous seminal report on prostate cancer mortality comparing screened men to controls. Now with 13 years follow-up, the rate ratio of prostate cancer mortality was 0.79 favoring the screened population. The authors concluded that there was a “substantial reduction in prostate cancer mortality attributable to testing with prostate-specific antigen (PSA)” but they also stated that a “quantification of harms” needed to be addressed. The issue of harms was not addressed by the ERSPC (at least not in this report) and hence this additional statement most likely reflects the controversy currently surrounding the risks associated with over-diagnosis and treatment of indolent diseases inadvertently detected by a screening protocol.1 In addition, the positive results from this trial conflict with those of the prostate, lung, colorectal and ovarian (PLCO)2 study and require further elaboration.