Associations Between iCOGS Single Nucleotide Polymorphisms and Upgrading in Both Surgical and Active Surveillance Cohorts of Men with Prostate Cancer

Abstract

Background: Associations have been documented recently between some of the 23 single nucleotide polymorphisms newly discovered with the Collaborative Oncological Gene-environment Study iCOGS array that indicate prostate cancer (PCa) risk and aspects of disease aggressiveness. The utility of these iCOGS SNPs remains to be determined in active surveillance (AS).

Objective: To determine associations between iCOGS SNPs and upgrading among men who underwent surgical treatment and AS for low-risk PCa.

Design, setting, and participants: The genotypes of the 23 iCOGS SNPs were determined for all white subjects with biopsy Gleason score (GS) 6 including 950 men who underwent definitive treatment with surgery and 209 men who elected AS. The clinical and pathologic characteristics were documented for all subjects.

Outcome measures and statistical analysis: Men who underwent surgery were grouped according to their pathologic GS (upgraded was defined as GS ≥7; nonupgraded remained GS 6). Men who were enrolled in AS were also grouped according to their GS on subsequent surveillance biopsies. Statistical analyses were performed comparing the genotypes between the upgraded and nonupgraded groups.

Results and limitations: Overall, 31% and 34% of men were upgraded in the surgery and AS cohorts, respectively. Three iCOGS SNPs were significantly associated with the risk of upgrading in the surgical cohort. After correction for multiple testing, only rs11568818 on chromosome 11q22 remained significantly associated with upgrading. Assessment of this allele in the AS cohort reveals that it was present at noteworthy higher frequencies in men with high-grade disease on surveillance biopsies compared with nonupgraded men (p=0.003). This study was primarily limited by the homogeneous patient population.

Conclusions: This is the first report of a SNP on chromosome 11q22 associated with higher grade disease in a surgical cohort that is also validated for eventual upgrading in a prospective AS cohort.

Patient summary: We examined the relationship between a group of genetic markers and prostate cancer (PCa) aggressiveness in a group of patients who underwent surgery for PCa and a group of patients who were enrolled in active surveillance. We found that these genetic markers helped predict which patients had more aggressive disease in both groups.

Keywords: Active surveillance; Genetics; Prostate cancer; Single nucleotide polymorphisms.