Background:
Melanoma and prostate cancer may share risk factors. This study determines if variants in melanoma-associated pigmentary genes are associated with serum prostate specific antigen (PSA).
Methods:
We analysed baseline data and bloods from the Concord Health and Ageing in Men Project participants aged 70+ years and without a diagnosis of prostate disease (n=1033). We selected and genotyped variants in MC1R (rs1805007, rs1805008), ASIP (rs4911414, rs1015362), SLC45A2 (rs28777, rs16891982), IRF4 (rs12203592), TYRP1 (rs1408799), TYR (rs1126809, rs1042602), SLC24A2 (rs12896399), and OCA2 (rs7495174). Birth regions were categorised as Australia/New Zealand (ANZ), Europe or elsewhere. Generalised linear dominant models with Poisson distribution, log link functions and robust variance estimators estimated adjusted percentage differences (%PSA) in mean serum PSA levels (ng/mL) between variant and wildtype (0%PSA=reference) genotypes for each birth regions, adjusting for age, body mass index, and serum 25OHD levels.
Results:
The proportions with variants at different loci varied among birth regions. Mean PSA levels were lower in Europe-born (-29.7%) and elsewhere-born (-11.7%) men than ANZ men. Lower %PSA was observed in men with variants in SLC45A2: rs28777 (-19.6;95%CI:-33.5,-2.7) and rs16891982 (-17.3;95%CI:-30.4,-1.7), principally in men born in ANZ and Europe. %PSA also varied among birth regions (p-interaction<0.05) for rs1805007(MC1R) – ANZ +23.7 (95%CI:-6.2,+63.1), Europe -45.6% (95%CI:-59.8,-26.3), elsewhere -21.4 (95%CI:-59.0,+50.4); and rs4911414(ASIP) – ANZ +33.7 (95%CI:+9.8,+62.9), Europe -9.7 (95%CI:-27.2,+12.0), elsewhere -40.4 (95%CI:-66.4,+5.8).
Conclusion:
Serum PSA levels in men vary by birth region and also vary with variants in the SLC45A2, MC1R and ASIP genes.
Impact:
These findings suggest that variants in melanoma-associated pigmentary genes are associated with PSA levels.