男性维生素D状态及癌症发病率和死亡率预测因素的前瞻性研究。

Prospective study of predictors of vitamin D status and cancer incidence and mortality in men.

作者信息

Giovannucci Edward, Liu Yan, Rimm Eric B, Hollis Bruce W, Fuchs Charles S, Stampfer Meir J, Willett Walter C

机构信息

Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.

出版信息

J Natl Cancer Inst. 2006 Apr 5;98(7):451-9. doi: 10.1093/jnci/djj101.

DOI:10.1093/jnci/djj101

PMID:16595781

Abstract

BACKGROUND

Vitamin D has potent anticancer properties, especially against digestive-system cancers. Many human studies have used geographic residence as a marker of solar ultraviolet B and hence vitamin D exposure. Here, we considered multiple determinants of vitamin D exposure (dietary and supplementary vitamin D, skin pigmentation, adiposity, geographic residence, and leisure-time physical activity-to estimate sunlight exposure) in relation to cancer risk in the Health Professionals Follow-Up Study.

METHODS

Among 1095 men of this cohort, we quantified the relation of these six determinants to plasma 25-hydroxy-vitamin D [25(OH)D] level by use of a multiple linear regression model. We used results from the model to compute a predicted 25(OH)D level for each of 47,800 men in the cohort based on these characteristics. We then prospectively examined this variable in relation to cancer risk with multivariable Cox proportional hazards models.

RESULTS

From 1986 through January 31, 2000, we documented 4286 incident cancers (excluding organ-confined prostate cancer and nonmelanoma skin cancer) and 2025 deaths from cancer. From multivariable models, an increment of 25 nmol/L in predicted 25(OH)D level was associated with a 17% reduction in total cancer incidence (multivariable relative risk [RR] = 0.83, 95% confidence interval [CI] = 0.74 to 0.92), a 29% reduction in total cancer mortality (RR = 0.71, 95% CI = 0.60 to 0.83), and a 45% reduction in digestive-system cancer mortality (RR = 0.55, 95% CI = 0.41 to 0.74). The absolute annual rate of total cancer was 758 per 100,000 men in the bottom decile of predicted 25(OH)D and 674 per 100,000 men for the top decile; these respective rates were 326 per 100,000 and 277 per 100,000 for total cancer mortality and 128 per 100,000 and 78 per 100,000 for digestive-system cancer mortality. Results were similar when we controlled further for body mass index or physical activity level.

CONCLUSIONS

Low levels of vitamin D may be associated with increased cancer incidence and mortality in men, particularly for digestive-system cancers. The vitamin D supplementation necessary to achieve a 25(OH)D increment of 25 nmol/L may be at least 1500 IU/day.

摘要

背景

维生素D具有强大的抗癌特性，尤其是对消化系统癌症。许多人体研究将地理居住地作为太阳紫外线B以及由此推断的维生素D暴露情况的一个指标。在此，我们在健康专业人员随访研究中，考量了维生素D暴露的多个决定因素（膳食和补充维生素D、皮肤色素沉着、肥胖、地理居住地以及休闲时间体力活动——用于估计阳光暴露）与癌症风险的关系。

方法

在该队列的1095名男性中，我们使用多元线性回归模型量化了这六个决定因素与血浆25-羟基维生素D [25(OH)D]水平的关系。我们利用该模型的结果，根据这些特征为队列中的47,800名男性计算出预测的25(OH)D水平。然后，我们使用多变量Cox比例风险模型前瞻性地研究了这个变量与癌症风险的关系。

结果

从1986年到2000年1月31日，我们记录了4286例新发癌症（不包括器官局限性前列腺癌和非黑色素瘤皮肤癌）以及2025例癌症死亡病例。从多变量模型来看，预测的25(OH)D水平每增加25 nmol/L，总癌症发病率降低17%（多变量相对风险[RR]=0.83，95%置信区间[CI]=0.74至0.92），总癌症死亡率降低29%（RR=0.71，95% CI=0.60至0.83），消化系统癌症死亡率降低45%（RR=0.55，95% CI=0.41至0.74）。预测的25(OH)D水平处于最低十分位数的男性中，总癌症的绝对年发病率为每10万人758例，而处于最高十分位数的男性中为每10万人674例；总癌症死亡率分别为每10万人326例和277例，消化系统癌症死亡率分别为每10万人128例和78例。当我们进一步控制体重指数或体力活动水平时，结果相似。