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Cancer Causes Control. 2018 Nov;29(11):1073-1080. doi: 10.1007/s10552-018-1081-5. Epub 2018 Oct 10.

Mendelian randomization does not support serum calcium in prostate cancer risk.

Author information

1
MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
2
Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
3
Department of Preventive Medicine, School of Medicine, University of São Paulo, São Paulo, Brazil.
4
National Institute for Health Research (NIHR) Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and the University of Bristol, Bristol, UK.
5
MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK. S.J.Lewis@bristol.ac.uk.
6
Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. S.J.Lewis@bristol.ac.uk.

Abstract

PURPOSE:

Observational 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.

METHODS:

A genetic instrument was constructed using five single-nucleotide polymorphisms robustly associated with serum calcium in a genome-wide association study (n ≤ 61,079). This instrument was then used to test the effect of a 0.5 mg/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).

RESULTS:

We found weak evidence for a protective effect of serum calcium on prostate cancer risk (odds ratio [OR] per 0.5 mg/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 0.5 mg/dL increase in calcium: 0.98, 95% CI 0.57-1.70; p = 0.93).

CONCLUSIONS:

Our Mendelian randomization analysis does not support the hypothesis that serum calcium increases risk of overall or advanced prostate cancer.

KEYWORDS:

Calcium; Diet; Mendelian randomization; Nutrition; Prostate cancer

PMID:
30306355
PMCID:
PMC6245088
DOI:
10.1007/s10552-018-1081-5
[Indexed for MEDLINE]
Free PMC Article

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