Genome-Wide Association Scan for Variants Associated with Early-Onset Prostate Cancer

Abstract

Prostate cancer is the most common non-skin cancer and the second leading cause of cancer related mortality for men in the United States. There is strong empirical and epidemiological evidence supporting a stronger role of genetics in early-onset prostate cancer. We performed a genome-wide association scan for early-onset prostate cancer. Novel aspects of this study include the focus on early-onset disease (defined as men with prostate cancer diagnosed before age 56 years) and use of publically available control genotype data from previous genome-wide association studies. We found genome-wide significant (p<5×10−8) evidence for variants at 8q24 and 11p15 and strong supportive evidence for a number of previously reported loci. We found little evidence for individual or systematic inflated association findings resulting from using public controls, demonstrating the utility of using public control data in large-scale genetic association studies of common variants. Taken together, these results demonstrate the importance of established common genetic variants for early-onset prostate cancer and the power of including early-onset prostate cancer cases in genetic association studies.

Assessing the Cumulative Contribution of New and Established Common Genetic Risk Factors to Early-Onset Prostate Cancer

“…We repeated these analyses for 40 previously established PCa variants for populations of European descent summarized in Goh et al (29) (see Supplementary Table 1 for variant identities and their respective imputation quality). The individual association results for these 40 variants in UM-PCGP subjects have been reported previously (21). Finally, we calculated weighted and unweighted totals of risk alleles across all 63 variants.…”

“…Initial genotyping quality control (QC) methodology was uniformly applied to all GWAS variants and samples (see Lange et al (21) for details). Subjects missing >5% of variant genotyping calls across all GWAS variants were excluded from consideration.…”

“…Several studies have demonstrated the importance of the previously established common variants to early-onset and familial PCa (12,21-25). Herein, we first test whether these 23 new variants are associated with early-onset PCa (20).…”

Impact of FTO SNPs rs9930506 and rs9939609 in Prostate Cancer Severity in a Cohort of Puerto Rican Men

“…In the Puerto Rican population being older than 60 years old is a risk factor for PCa as reported by Soto-Salgado et al [52]. Besides that, there have been reports (Hussein et al) that show that PCa may appear early in life (≤ 55 years old) [53], and that this early PCa onset may be associated and promoted by several genes [54]. Furthermore, these researchers state that PCa may remain undetectable in its early stages for many years until different factors like obesity, propitiate its development to a more aggressive stage [49,53,54].…”

“…Besides that, there have been reports (Hussein et al) that show that PCa may appear early in life (≤ 55 years old) [53], and that this early PCa onset may be associated and promoted by several genes [54]. Furthermore, these researchers state that PCa may remain undetectable in its early stages for many years until different factors like obesity, propitiate its development to a more aggressive stage [49,53,54]. In our cohort, the mean age at PCa diagnosis was 58 years old, particularly in the overweight group, which could suggest an agreement with Hussein [53].…”