Using Genetic Proxies for Lifecourse Sun Exposure to Assess the Causal Relationship of Sun Exposure with Circulating Vitamin D and Prostate Cancer Risk
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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DOI：
10.1158/1055-9965.epi-12-1248
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发表时间：
2013-04-01
影响因子：
3.8
通讯作者：
Martin, Richard M.
中科院分区：
文献类型：
--
作者：
Bonilla, Carolina;Gilbert, Rebecca;Martin, Richard M.
背景资料：生态学和流行病学研究发现，阳光照射的强度和持续时间与前列腺癌呈负相关，这可能是由于维生素D合成减少。色素性状影响阳光照射，因此可能影响前列腺癌的风险。由于观察性研究容易受到混淆和测量误差的影响，我们使用孟德尔随机化方法来研究阳光照射与前列腺癌风险和中间表型的关系，即维生素D的血浆水平。方法：我们创建了晒黑，肤色和雀斑评分作为先前与这些表型相关的单核苷酸多态性的组合。分数越高，表明倾向于烧伤，有较浅的肤色和雀斑。这些分数与维生素D水平进行了相关性测试（25-羟基维生素-D和1，25-二羟基维生素-D）和前列腺特异性抗原在参加前列腺癌症检测和治疗（ProtecT）研究的3，123名白色英国人中检测到前列腺癌。95%CI，-0.52%至-0.01%]，晒黑评分与前列腺癌风险呈正相关（OR 1.05; 95%CI，1.02-1.09），调整人群分层和潜在混杂因素后。倾向于烧伤的人更有可能在阳光下呆的时间更少，因此血浆维生素D水平较低，影响：色素沉着相关的遗传评分的使用是有价值的评估的潜在好处，阳光照射相对于前列腺癌的风险。癌症流行病学生物标志物Prev; 22（4）; 597-606。(C)2013年AACR。
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.Impact: 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. Cancer Epidemiol Biomarkers Prev; 22(4); 597-606. (C) 2013 AACR.