循環維生素D水平與7種癌症發病無關，補充維生素D防癌尚無依據

循環維生素D濃度和七種癌症的風險：孟德爾隨機化研究

摘 要

目的 ：確定維生素D的循環濃度是否與癌症風險有因果關係。

OBJECTIVE：To determine if circulating concentrations of vitamin D are causally associated with risk of cancer.

設計：孟德爾隨機研究。

DESIGN：Mendelian randomisation study.

設置：大型遺傳流行病學網路（腫瘤遺傳學協會和機制（GAMEON），結腸直腸癌協會（GECCO）的遺傳和流行病學以及前列腺癌協會組織調查癌症相關的基因組改變（PRACTICAL）聯盟）和MR - 基礎平台）。

SETTING：Large genetic epidemiology networks (the Genetic Associations and Mechanisms in Oncology (GAMEON), the Genetic and Epidemiology of Colorectal Cancer Consortium (GECCO), and the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortiums, and the MR-Base platform).

參與者：70 563例癌症（22 898例前列腺癌，15 748例乳腺癌，12 537例肺癌，11 488例結直腸癌，4369例卵巢癌，1896例胰腺癌和1627例神經母細胞瘤）和84 418例對照。

PARTICIPANTS：70 563 cases of cancer (22 898 prostate cancer, 15 748 breast cancer, 12 537 lung cancer, 11 488 colorectal cancer, 4369 ovarian cancer, 1896 pancreatic cancer, and 1627 neuroblastoma) and 84 418 controls.

風險承擔：與維生素D有關的四個單核苷酸多態性（rs2282679，rs10741657，rs12785878和rs6013897）用於確定循環25-羥基維生素D（25（OH）D）濃度的多重多態性評分。

EXPOSURES：Four single nucleotide polymorphisms (rs2282679, rs10741657, rs12785878 and rs6013897) associated with vitamin D were used to defne a multipolymorphism score for circulating 25-hydroxyvitamin D (25(OH)D) concentrations.

主要結局評估：主要結果是結直腸癌，乳腺癌，前列腺癌，卵巢癌，肺癌和胰腺癌以及神經母細胞瘤的風險，用特異性多態性與基於可能性方法的關聯的逆方差加權平均來評估風險。根據性別、解剖部位、分期和組織學的癌症亞型的次要結果也進行了檢查。

MAIN OUTCOMES MEASURES：The primary outcomes were the risk of incident colorectal, breast, prostate, ovarian, lung, and pancreatic cancer and neuroblastoma, which was evaluated with an inverse variance weighted average of the associations with specifc polymorphisms anda likelihood based approach.Secondary outcomes based on cancer subtypes by sex, anatomic location, stage, and histology were also examined.

結果：幾乎沒有證據表明25（OH）D的多態多態性評分與七種癌症或其亞型中的任何一種的風險相關。具體而言，遺傳決定的25（OH）D濃度每25nmol / L增加的比值比為0.92（95％置信區間0.76至1.10），乳腺癌1.05（0.89至1.24），乳腺癌0.89（0.77至1.02）為前列腺癌，1.03（0.87到1.23）用於肺癌。結果與兩種不同的分析方法是一致的，並且該研究有助於檢測中等程度的相對效應大小（例如，在大多數原發癌癥結果中，25（OH）D的每25nmol / L下降1.20-1.50。似乎沒有違反孟德爾隨機假設。

RESULTS：There was little evidence that the multi-polymorphism score of 25(OH)D was associated with risk of any of the seven cancers or their subtypes.Specifcally, the odds ratios per 25 nmol/L increase in genetically determined 25(OH)D concentrations were 0.92(95% confdence interval 0.76 to 1.10) for colorectal cancer, 1.05 (0.89 to 1.24) for breast cancer, 0.89(0.77 to 1.02) for prostate cancer, and 1.03 (0.87to 1.23) for lung cancer.The results were consistent with the two di?erent analytical approaches, and the study was powered to detect relative e?ect sizes of moderate magnitude (for example, 1.20-1.50 per 25 nmol/L decrease in 25(OH)D for most primary cancer outcomes. The Mendelian randomisation assumptions did not seem to be violated.

結論：幾乎沒有證據表明循環維生素D濃度與各種癌症風險之間存在線性因果關係，儘管不能排除存在低級別因果臨床相關影響。這些結果與以前的文獻相結合，提供證據表明，目前不應該推薦人群範圍內篩選維生素D缺乏症和隨後廣泛的維生素D補充作為預防癌症的策略。

CONCLUSIONS：There is little evidence for a linear causal association between circulating vitamin D concentration and risk of various types of cancer, though the existence of causal clinically relevant e?ects of low magnitude cannot be ruled out.These results, in combination with previous literature, provide evidence that population-wide screening for vitamin D defciency and subsequent widespread vitamin D supplementation should not currently be recommended as a strategy for primary cancer prevention.

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