Mendelian randomization does not support serum calcium in prostate cancer risk

被引：8

作者：

Yarmolinsky, James ^{[1
,2
]}

Berryman, Katie ^{[1
,2
]}

Langdon, Ryan ^{[1
,2
]}

Bonilla, Carolina ^{[1
,2
,3
]}

Smith, George Davey ^{[1
,2
,4
,5
]}

Martin, Richard M. ^{[1
,2
,4
,5
]}

Lewis, Sarah J. ^{[1
,2
]}

机构：

[1] Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, Avon, England

[2] Univ Bristol, Bristol Med Sch, Populat Hlth Sci, Bristol, Avon, England

[3] Univ Sao Paulo, Dept Prevent Med, Sch Med, Sao Paulo, Brazil

[4] Univ Hosp Bristol NHS Fdn Trust, NIHR, Bristol Biomed Res Ctr, Bristol, Avon, England

[5] Univ Bristol, Bristol, Avon, England

来源：

CANCER CAUSES & CONTROL | 2018年 / 29卷 / 11期

基金：

英国医学研究理事会;

关键词：

Diet; Nutrition; Calcium; Prostate cancer; Mendelian randomization; VITAMIN-D; NATIONAL-HEALTH; DAIRY-PRODUCTS; GROWTH-FACTORS; MORTALITY; INSTRUMENTS; NUTRITION; INSULIN; EPIDEMIOLOGY; METAANALYSIS;

D O I：

10.1007/s10552-018-1081-5

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

PurposeObservational studies suggest that dietary and serum calcium are risk factors for prostate cancer. However, such studies suffer from residual confounding (due to unmeasured or imprecisely measured confounders), undermining causal inference. Mendelian randomization uses randomly assigned (hence unconfounded and pre-disease onset) germline genetic variation to proxy for phenotypes and strengthen causal inference in observational studies. We tested the hypothesis that serum calcium is associated with an increased risk of overall and advanced prostate cancer.MethodsA genetic instrument was constructed using five single-nucleotide polymorphisms robustly associated with serum calcium in a genome-wide association study (n61,079). This instrument was then used to test the effect of a 0.5mg/dL increase (1 standard deviation, SD) in serum calcium on risk of prostate cancer in 72,729 men in the PRACTICAL (Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome) Consortium (44,825 cases, 27,904 controls) and risk of advanced prostate cancer in 33,498 men (6,263 cases, 27,235 controls).ResultsWe found weak evidence for a protective effect of serum calcium on prostate cancer risk (odds ratio [OR] per 0.5mg/dL increase in calcium: 0.83, 95% CI 0.63-1.08; p=0.12). We did not find strong evidence for an effect of serum calcium on advanced prostate cancer (OR per 0.5mg/dL increase in calcium: 0.98, 95% CI 0.57-1.70; p=0.93).ConclusionsOur Mendelian randomization analysis does not support the hypothesis that serum calcium increases risk of overall or advanced prostate cancer.

引用

页码：1073 / 1080

页数：8

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