Disentangling discordant vitamin D associations with prostate cancer incidence and fatality in a large, nested case–control study

Author:

Etiévant Lola1,Gail Mitchell H1ORCID,Albanes Demetrius2

Affiliation:

1. Division of Cancer Epidemiology and Genetics, Biostatistics Branch, National Cancer Institute , Rockville, MD, USA

2. Division of Cancer Epidemiology and Genetics, Metabolic Epidemiology Branch, National Cancer Institute , Rockville, MD, USA

Abstract

Abstract Background Published analyses of prostate cancer nested case–control and survival data in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study cohort suggested that men with higher baseline vitamin D [25(OH)D] concentrations have both (i) increased prostate cancer risk and (ii) decreased prostate cancer-specific fatality. Methods To investigate possible factors responsible for a spurious association with prostate cancer fatality, we reanalysed baseline serum vitamin D associations with prostate cancer risk and prostate cancer-specific fatality in case–control data nested within the ATBC Study (1000 controls and 1000 incident prostate cancer cases). Conditional logistic regression and Cox proportion hazard models were used, respectively, to estimate odds ratios for risk and hazard ratios for prostate cancer-specific fatality, overall and by disease aggressiveness. We replicated these case–control analyses using baseline serum measurements of alpha-tocopherol (vitamin E), beta-carotene and retinol (vitamin A), and used the entire ATBC Study cohort (n = 29 085) to estimate marginal associations between these baseline vitamins and prostate cancer incidence and fatality following blood collection. Results Vitamin D analyses agreed closely with those originally published, with opposite risk and fatality associations. By contrast, the analyses of alpha-tocopherol, beta-carotene and retinol yielded concordant associations for prostate cancer incidence and prostate cancer-specific fatality. Conclusions We found evidence of neither artefacts in the nested prostate cancer case–control data set nor detection or collider biases in the fatality analyses. The present findings therefore support a valid inverse (i.e. beneficial) association between vitamin D and prostate cancer-specific survival that warrants further evaluation, including possibly in controlled trials.

Funder

Division of Cancer Epidemiology and Genetics

National Institutes of Health, USA

Publisher

Oxford University Press (OUP)

Reference19 articles.

1. Serum 25-hydroxy vitamin D and prostate cancer risk in a large nested case-control study;Albanes;Cancer Epidemiol Biomarkers Prev,2011

2. Circulating 25-hydroxyvitamin D and prostate cancer survival;Mondul;Cancer Epidemiol Biomarkers Prev,2016

3. Collider bias undermines our understanding of COVID-19 disease risk and severity;Griffith;Nat Commun,2020

4. Collider bias in observational studies;Tönnies;Dtsch Arztebl Int,2022

5. Collider bias;Holmberg;JAMA,2022

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