title: Using genetic proxies for lifecourse sun exposure to assess the causal relationship of sun exposure with circulating vitamin d and prostate cancer risk.
abstract: BACKGROUND
  Ecological and epidemiological studies have identified an inverse association of intensity and duration of sunlight exposure with prostate cancer, which may be explained by a reduction in vitamin D synthesis. Pigmentation traits influence sun exposure and therefore may affect prostate cancer risk. Because observational studies are vulnerable to confounding and measurement error, we used Mendelian randomization to examine the relationship of sun exposure with both prostate cancer risk and the intermediate phenotype, plasma levels of vitamin D.
  
  
  METHODS
  We created a tanning, a skin color, and a freckling score as combinations of single nucleotide polymorphisms that have been previously associated with these phenotypes. A higher score indicates propensity to burn, have a lighter skin color and freckles. The scores were tested for association with vitamin D levels (25-hydroxyvitamin-D and 1,25-dihydroxyvitamin-D) and prostate-specific antigen detected prostate cancer in 3,123 White British individuals enrolled in the Prostate Testing for cancer and Treatment (ProtecT) study.
  
  
  RESULTS
  The freckling score was inversely associated with 25(OH)D levels [change in 25(OH)D per score unit -0.27; 95% CI, -0.52% to -0.01%], and the tanning score was positively associated with prostate cancer risk (OR = 1.05; 95% CI, 1.02-1.09), after adjustment for population stratification and potential confounders.
  
  
  CONCLUSIONS
  Individuals who tend to burn are more likely to spend less time in the sun and consequently have lower plasma vitamin D levels and higher susceptibility to prostate cancer.
  
  
  CONCLUSIONS
  The use of pigmentation-related genetic scores is valuable for the assessment of the potential benefits of sun exposure with respect to prostate cancer risk.
authors: School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, United Kingdom.
authors: Carolina
authors: C
authors: Bonilla
authors: Rebecca
authors: R
authors: Gilbert
authors: John P
authors: JP
authors: Kemp
authors: Nicholas J
authors: NJ
authors: Timpson
authors: David M
authors: DM
authors: Evans
authors: Jenny L
authors: JL
authors: Donovan
authors: Freddie C
authors: FC
authors: Hamdy
authors: David E
authors: DE
authors: Neal
authors: William D
authors: WD
authors: Fraser
authors: Smith George
authors: SG
authors: Davey
authors: Sarah J
authors: SJ
authors: Lewis
authors: Mark
authors: M
authors: Lathrop
authors: Richard M
authors: RM
authors: Martin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000209:etiology*; D012307:Risk Factors; D012880:Skin Pigmentation / Q000235:genetics*; D055108:Sunbathing; D013472:Sunlight / Q000009:adverse effects*; D014807:Vitamin D / Q000097:blood*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D014807:Vitamin D; D017430:Prostate-Specific Antigen