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

Autor: David Smith, Agata Chrzanowska, Robert G. Cumming, Markus J. Seibel, Visalini Nair-Shalliker, Sam Egger, Rebecca S. Mason, Louise M. Waite, Bruce K. Armstrong, David G. Le Couteur, David J. Handelsman
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Melanomas
Male
0301 basic medicine
Neoplasms
Radiation-Induced
Skin Neoplasms
Physiology
lcsh:Medicine
Skin Pigmentation
urologic and male genital diseases
Biochemistry
Radiation Tolerance
Geographical Locations
Prostate cancer
0302 clinical medicine
Reference Values
Medicine and Health Sciences
Testosterone
Lipid Hormones
lcsh:Science
Melanoma
Aged
80 and over
2. Zero hunger
Multidisciplinary
Prostate Cancer
Cancer Risk Factors
Environmental Causes of Cancer
Prostate Diseases
Dihydrotestosterone
3. Good health
Europe
Oncology
030220 oncology & carcinogenesis
Androgens
Sunlight
Cancer Type - Prostate Cancer
Anatomy
Research Article
medicine.drug
Neoplasms
Hormone-Dependent
medicine.drug_class
Urology
Prostatitis
Etiology - Exogenous Factors in the Origin and Cause of Cancer
Single-nucleotide polymorphism
03 medical and health sciences
Exocrine Glands
medicine
Humans
Genetic Predisposition to Disease
Risk factor
Aged
Models
Genetic
business.industry
lcsh:R
Australia
Cancers and Neoplasms
Biology and Life Sciences
Prostatic Neoplasms
Prostate-Specific Antigen
Overexposure to Sun
Androgen
medicine.disease
Hormones
Genitourinary Tract Tumors
111799 - Public Health and Health Services not elsewhere classified [FoR]
030104 developmental biology
People and Places
Prostate Gland
lcsh:Q
business
Body mass index
Genes
Neoplasm
New Zealand
Zdroj: PLoS ONE, Vol 13, Iss 3, p e0193893 (2018)
PLoS ONE
ISSN: 1932-6203
Popis: 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; pinteraction = 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 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).
Databáze: OpenAIRE
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