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Using genetic proxies for lifecourse sun exposure to assess the causal relationship of sun exposure with circulating vitamin d and prostate cancer risk.

ABSTRACT: 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.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.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.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.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.

SUBMITTER: Bonilla C

PROVIDER: S-EPMC3616836 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Using genetic proxies for lifecourse sun exposure to assess the causal relationship of sun exposure with circulating vitamin d and prostate cancer risk.

Bonilla Carolina C Gilbert Rebecca R Kemp John P JP Timpson Nicholas J NJ Evans David M DM Donovan Jenny L JL Hamdy Freddie C FC Neal David E DE Fraser William D WD Davey Smith George SG Lewis Sarah J SJ Lathrop Mark M Martin Richard M RM

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20130225 4

<h4>Background</h4>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 canc ...[more]

PMID: 23441100

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Project description:BackgroundThe relationship between gut microbiota and the occurrence of cholecystitis remains unclear. Existing research lacks a clear understanding of how circulating vitamin levels modulate this relationship. Therefore, our study aims to investigate whether circulating vitamin levels mediate the causal relationship between gut microbiota and cholecystitis using a two-step bidirectional Mendelian randomization approach.MethodsIn this study, we initially employed Linkage Disequilibrium Score Regression (LDSC) analysis to assess the genetic correlation of five circulating vitamin level genome-wide association study (GWAS) summary datasets, thereby avoiding potential sample overlap. Subsequently, we conducted a two-step analysis to investigate the causal effects between gut microbiota and cholecystitis. In the second step, we explored the causal relationship between circulating vitamin levels and cholecystitis and identified the mediating role of vitamin D. The primary method used for causal analysis was the inverse variance-weighted approach. We performed additional sensitivity analyses to ensure result robustness, including the cML-MA method and reverse Mendelian randomization (MR) analysis.ResultsAn increment of one standard deviation in RuminococcaceaeUCG003 was associated with a 25% increased risk of cholecystitis (OR = 1.25, 95%CI = 1.01-1.54, p = 0.04), along with a 3% decrease in 25-hydroxyvitamin D levels (OR = 0.97, 95%CI = 0.944-0.998, p = 0.04). However, following the rigorous Bonferroni correction, every one standard deviation decrease in circulating vitamin D levels was associated with a 33% increased risk of cholecystitis (OR = 0.67, 95%CI = 0.49-0.90, p = 0.008, Padjust = 0.04). Thus, the potential link between gut microbiota and cholecystitis risk might be mediated by circulating vitamin D levels (proportion mediated = 5.5%). Sensitivity analyses provided no evidence of pleiotropy.ConclusionOur study results suggest that an elevated abundance of specific gut microbiota is associated with an increased susceptibility to cholecystitis, with the causal relationship being mediated by circulating vitamin D levels. Further large-scale randomized controlled trials are necessary to validate the causal effects of gut microbiota on cholecystitis risk. This study provides novel insights into cholecystitis prevention through the regulation of gut microbiota.

Project description:Few detailed data are available on the wide range of determinants of vitamin D status among postmenopausal women, and it is also unclear whether there may be undiscovered determinants. The objective of this study was to comprehensively evaluate determinants of serum 25-hydroxyvitamin D [25(OH)D] concentrations in a large cohort of postmenopausal women. Data from a subset of the Women's Health Initiative Observational Study were analyzed (50-79 y; n = 3345). Information on diet, lifestyle behaviors, secondhand smoke, use of dietary supplements and medication, chronic diseases, and anthropometry was collected at baseline (1993-1998) and on sun exposure at year 4 follow-up. Linear regression was performed to estimate regression coefficients (?). Significant determinants were total vitamin D intake (food plus supplements per 100 IU/d, ? = 2.08), years of supplemental vitamin D use (? = 0.15), total fat intake (grams per day, ? = -0.03), smoking status (? = -2.64, current vs. never), regional solar irradiance (? = 6.26, 475-500 vs. 300-325 Langleys), daylight time spent outdoors in summer (? = 5.15, >2 h vs. <30 min/d), recreational physical activity (metabolic equivalent task per hour per week, ? = 0.13), waist circumference (centimeters, ? = -0.26), and race/ethnicity (? = -11.94, black vs. white). Total vitamin D intake (partial R(2) = 0.09) explained the most variance in serum 25(OH)D concentrations (total R(2) = 0.29). The association between total vitamin D intake and serum 25(OH)D concentrations was stronger among participants who spent less rather than more daylight time outdoors in summer (P-interaction = 0.026). History and medications for hypertension, hyperlipidemia, and type 2 diabetes and secondhand smoke exposure were not associated with serum 25(OH)D. In conclusion, dietary factors and sun exposure remain important determinants of vitamin D status in postmenopausal women. Vitamin D intake should be emphasized for those with limited sun exposure.

Dataset Information

Using genetic proxies for lifecourse sun exposure to assess the causal relationship of sun exposure with circulating vitamin d and prostate cancer risk.

Publications

Using genetic proxies for lifecourse sun exposure to assess the causal relationship of sun exposure with circulating vitamin d and prostate cancer risk.

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