Associations between sun sensitive pigmentary genes and serum prostate specific antigen levels

Visalini Nair-Shalliker; Sam Egger; Agata Chrzanowska; Rebecca Mason; Louise Waite; David Le Couteur; Markus J Seibel; David J Handelsman; Robert Cumming; David P Smith; Bruce K Armstrong

doi:10.1371/journal.pone.0193893

Associations between sun sensitive pigmentary genes and serum prostate specific antigen levels

PLoS One. 2018 Mar 8;13(3):e0193893. doi: 10.1371/journal.pone.0193893. eCollection 2018.

Authors

Visalini Nair-Shalliker^{1

2

3}, Sam Egger¹, Agata Chrzanowska², Rebecca Mason⁴, Louise Waite⁵, David Le Couteur⁵, Markus J Seibel⁵, David J Handelsman⁵, Robert Cumming^{2

5

6}, David P Smith^{1

2

7}, Bruce K Armstrong^{2

8}

Affiliations

¹ Cancer Research Division, Cancer Council New South Wales, Sydney, Australia.
² Sydney School of Public Health, The University of Sydney, Sydney, Australia.
³ Department of Clinical Medicine, Macquarie University, Sydney, Australia.
⁴ Sydney Medical School, The University of Sydney, Sydney, Australia.
⁵ Centre for Education and Research on Ageing, Concord Hospital and The University of Sydney, Sydney, New South Wales, Australia.
⁶ ANZAC Research Institute, The University of Sydney, Sydney, New South Wales, Australia.
⁷ Menzies Health Institute Queensland, Griffith University, Southport, Queensland, Australia.
⁸ School of Population Health, University of Western Australia, Perth, Western Australia, Australia.

Abstract

Background: Melanoma and prostate cancer may share risk factors. This study examined the association between serum PSA levels, which is a risk factor for prostate cancer, and variants in some melanoma-associated pigmentary genes.

Methods: We studied participants, all aged 70+ years, in the Concord Health and Ageing in Men Project who had no history of prostatitis or received treatment for prostate disease (n = 1033). We genotyped variants in MC1R (rs1805007, rs1805008), ASIP (rs4911414, rs1015362), SLC45A2 (rs28777, rs16891982), IRF4 (rs12203592), TYRP1 (rs1408799), TYR (rs1126809, rs1042602), SLC24A2 (rs12896399), and OCA2 (rs7495174). 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, adjusting for age, body mass index, serum 25OHD levels and birth regions (Australia or New Zealand (ANZ), Europe or elsewhere).

Results: Serum PSA levels were strongly associated with advancing age and birth regions: mean PSA levels were lower in Europe-born (-29.7%) and elsewhere-born (-11.7%) men than ANZ-born men (reference). Lower %PSA was observed in men with variants in SLC45A2: rs28777 (-19.6;95%CI: -33.5, -2.7), rs16891982 (-17.3;95%CI:-30.4,-1.7) than in wildtype men (reference). There were significant interactions between birth regions and PSA levels in men with variants in MC1R (rs1805007; p-interaction = 0.0001) and ASIP (rs4911414; p-interaction = 0.007). For these genes %PSA was greater in ANZ-born men and lower in Europe- and elsewhere-born men with the variant than it was in wildtype men. In a post hoc analysis, serum testosterone levels were increased in men with MC1R rs1805007 and serum dihydrotestosterone in men with ASIP rs1015362.

Conclusion: Men with SNPs in SLC45A2, who have less sun sensitive skin, have lower PSA levels. Men with SNPs in MC1R and ASIP, who have more sun sensitive skin, and were born in ANZ, have higher PSA levels. Androgens may modify these apparent associations of pigmentary genes and sun exposure with PSA levels.

Impact: PSA levels and possibly prostate cancer risk may vary with sun sensitivity and sun exposure, the effects of which might be modified by androgen levels.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Androgens*
Australia
Dihydrotestosterone / blood
Europe / ethnology
Genes, Neoplasm
Genetic Predisposition to Disease
Humans
Male
Melanoma / genetics*
Models, Genetic
Neoplasms, Hormone-Dependent / genetics*
Neoplasms, Radiation-Induced / genetics*
New Zealand
Prostate-Specific Antigen / blood*
Prostatic Neoplasms / genetics*
Radiation Tolerance / genetics
Reference Values
Skin Neoplasms / genetics*
Skin Pigmentation / genetics*
Sunlight / adverse effects*
Testosterone / blood

Substances

Androgens
Dihydrotestosterone
Testosterone
Prostate-Specific Antigen

Grants and funding

This project was funded by the Cancer Council New South Wales project grant (512513 awarded to Prof Armstrong) and the National Health and Medical Research Council (NHMRC) project grant (301916 awarded to Prof Cumming). A/Prof D Smith was supported by a grant from Cancer Institute NSW (#15/CDF/1-10).