SNPs in Genes Affect Quality of Life Related to Radiation in Men with Prostate Cancer

Phoebe Starr

March 2013, Vol 4, No 3 - Personalized Medicine

Orlando, FL—Novel candidate single nucleotide polymorphisms (SNPs) in genes that are associated with inflammation have been identified and will be explored further with regard to their role in long-term quality-of-life (QOL) effects of radiation in men with prostate cancer, according to new research presented at the 2013 Genitourinary Cancers Symposium. The investigators found 7 SNPs that were significantly associated with long-term QOL outcomes after radiation, but these SNPs did not retain statistical significance in a comparator group of men treated with radical prostatectomy.

“Men with prostate cancer have significant decrements in quality of life, which may be related to genetic differences. In particular, inflammation-related genes may impact long-term toxicity following radiation therapy, including esophagitis and pneumonitis,” stated lead investigator Jonathan D. Schoenfeld, MD, MPH, a radiation oncology resident at Harvard Radia­tion Oncology Program, Harvard Medi­cal School, Boston. “We have con­firmed significant associations with SNPs and quality of life in men treated with radiotherapy, and these associations require prospective assessment regarding their relationship to QOL.”

The study was based on blood samples collected from men who were diagnosed with prostate cancer and were treated with radiation between 1982 and 2006. All men were enrolled in the prospective US Physicians’ Health Study (PHS), a randomized trial of aspirin and beta-carotene. Using the additive model, 43 SNPs in 10 inflammation-related genes (previously found to be associated with prostate cancer) were genotyped and analyzed.

A total of 264 men with confirmed cases of prostate cancer were given questionnaires at intervals between 2005 and 2007, at a median of 6 years after diagnosis. The questionnaires followed QOL outcomes about the symptoms that were experienced during the years since diagnosis and radiation, including decreased force of urinary stream, increased urinary frequency or urgency, rectal urgency, and impotence. In addition, medical records were obtained and reviewed.

The first cohort was specifically limited to men with nonmetastatic prostate cancer who were treated with definitive radiation. A second cohort of 337 men who were treated with definitive radical prostatectomy served as a comparison group.

“We limited excluded analysis to Caucasian men and excluded other races,” noted Dr Schoenfeld. The first cohort of 264 men (median age, 72 years) treated with radiation were predominantly low-risk patients. Of this cohort, 61% of the patients had Gleason scores of <7; 98% were in early clinical stage.

The investigators identified 13 SNPs that are significantly associated with QOL. On multivariate analysis, 7 SNPs remained statistically significant and were found on the genes IL8 (1 SNP), NFKB (2 SNPs), RNase L (2 SNPs), CRP (1 SNP), and TLR 10 (1 SNP).

Between 20% and 29% of the patients reported severe urinary and rectal symptoms, and 72% reported severe impotence. Between 71% and 80% of the patients reported mild or nonexistent urinary and rectal symptoms, and 28% reported mild or nonexistent impotence.

In the second cohort of 337 men from the PHS who were treated with radical prostatectomy, 71% had Gleason scores of <7, and 95% were in early stage. The baseline characteristics and QOL results between the radiation and surgical patients were not comparable. Be­tween 9% and 15% of the patients had urinary or rectal symptoms, and 82% had moderate-to-severe impotence.

“None of the 7 SNPs that were statistically significantly associated with the 4 parameters of QOL retained their statistical significance in men treated with radical prostatectomy,” Dr Schoenfeld pointed out. “The study is hypothesis generating. The mechanism of action of the selected genes is currently unknown. We performed incomplete sequencing of SNPs we tested.”