rs10505483 (CASC19, PCAT1): Prostate Cancer Risk

Key takeaways

• rs10505483 falls within a genomic region (CASC19, PCAT1) studied in relation to prostate cancer susceptibility across multiple racial and ethnic groups.
• The large majority of established prostate cancer risk variants show positive associations with prostate cancer in both Japanese (79%) and Latino (88%) populations.
• The cumulative per-allele odds ratio for established prostate cancer risk variants is approximately 1.10 in Japanese populations (P=2.71x10-25) and 1.07 in Latinos (P=1.02x10-16).
• Large-scale proteome-wide analyses of cancer predisposition reveal that roughly 44% of gene-cancer associations reflect protective rather than risk-elevating effects.
• Standard additive genetic models used in genome-wide association studies may not capture recessive inheritance, which accounts for approximately 46% of cancer predisposition signals in proteome-wide analyses.

What the research says A two-stage genome-wide association study (GWAS) of prostate cancer in Japanese (stage 1: 1,033 cases and 1,042 controls; stage 2: 1,583 cases and 3,386 controls from BioBank Japan) and Latino (stage 1: 1,043 cases and 1,057 controls) populations from the Multiethnic Cohort found that 79% and 88% of established prostate cancer risk variants, respectively, were positively associated with prostate cancer, with cumulative per-allele odds ratios of 1.10 (P=2.71x10-25) for Japanese and 1.07 (P=1.02x10-16) for Latinos. A proteome-wide association study (PWAS), which tests genetic associations mediated by alterations in protein function, of nine cancer types in approximately 500,000 UK Biobank participants identified 110 significant gene-cancer associations across 70 genomic regions, finding that 44% of those associations were linked to reduced rather than elevated cancer risk and that 46% of cancer-associated regions exhibited exclusively recessive inheritance.

Reported associations

• Prostate cancer risk (Japanese and Latino cohorts): A multi-ethnic GWAS found that 79% of established risk variants were positively associated with prostate cancer in Japanese populations and 88% in Latinos, with cumulative per-allele odds ratios of 1.10 for Japanese (P=2.71x10-25) and 1.07 for Latinos (P=1.02x10-16), based on stage 1 samples of approximately 2,075 Japanese and 2,100 Latino participants.
• Cancer predisposition (proteome-wide UK Biobank): A PWAS in approximately 500,000 UK Biobank individuals identified 110 significant gene-cancer associations across 70 genomic regions and nine cancer types, with 44% of associations linked to reduced cancer risk (protective effects) and 46% of cancer-associated regions showing exclusively recessive inheritance patterns.

Evidence quality The multi-ethnic prostate cancer GWAS used a two-stage design; stage 1 enrolled approximately 2,075 Japanese and 2,100 Latino individuals, while stage 2 added 4,969 Japanese participants from BioBank Japan and 3,748 participants from a UK case-control study. No novel genome-wide significant variants outside previously known risk regions were identified, and a putative novel association at chromosome 2q33 in Japanese did not replicate at stage 2, illustrating the challenge of discovering genuinely new risk loci. The UK Biobank PWAS leveraged a far larger sample of approximately 500,000 individuals; the study authors note that GWAS efforts in cancer predisposition are far from saturated, meaning current findings may be revised as cohort sizes grow. The two studies use fundamentally different methodologies (additive variant-level association models versus gene-level protein function modeling) and address different aspects of cancer risk, so direct comparison is limited. No conflicting findings about the same genomic locus are reported across the two studies.

Lifestyle considerations No lifestyle considerations on file for this variant.