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

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 (he...

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Publicado en:Cancer Causes & Control Vol. 29; no. 11; pp. 1073 - 1081
Autores principales: Yarmolinsky, James, Berryman, Katie, Langdon, Ryan, Bonilla, Carolina, PRACTICAL consortium, Davey Smith, George, Martin, Richard M., Lewis, Sarah J.
Formato: Journal Article
Publicado: Springer Nature Nov2018
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Nov2018
      vid: 29
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      pub: Springer Nature
      place: New York, New York
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        atl: Mendelian randomization does not support serum calcium in prostate cancer risk.
      aug:
        au:
          Yarmolinsky, James
          Berryman, Katie
          Langdon, Ryan
          Bonilla, Carolina
          PRACTICAL consortium
          Davey Smith, George
          Martin, Richard M.
          Lewis, Sarah J.
        affil: MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK
      sug:
        subj:
          Prostatic Neoplasms Epidemiology
          Calcium, Dietary Blood
          Calcium Blood
          Prostatic Neoplasms Blood
          Polymorphism, Genetic
          Prostatic Neoplasms
          Genetics
          Male
          Phenotype
          Sequence Analysis
          Odds Ratio
          Prostatic Neoplasms Etiology
          Calcium, Dietary Adverse Effects
          Risk Factors
          Male
      ab: 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.
      pubtype: Academic Journal
      doctype: Journal Article
      ougenre: Article
    language: English
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