Multivitamin, calcium and folic acid supplements and the risk of colorectal cancer in Lynch syndrome.

International journal of epidemiology
Q1
Jun 2016
Citations:31
Influential Citations:2
Observational Studies (Human)
80
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Methods
1966 carriers of pathogenic germline mutations in MMR genes (719 MLH1, 931 MSH2, 211 MSH6, 105 PMS2) recruited to the Colon Cancer Family Registry from the USA, Canada, Australia and New Zealand between 1997 and 2012; 56% female; observational cohort; exposures self-reported via standardized questionnaires; time at risk started at birth and ended at CRC diagnosis or censoring age; weighted Cox proportional hazards regression to correct for ascertainment bias; multiple imputation for missing data; analyses adjusted for potential confounders and effect modifiers as described.
Intervention
Multivitamin: intake ≥2 times/week for ≥3 years (dosage not reported; self-reported weekly frequency). Calcium: intake ≥2 times/week for ≥3 years (dosage not reported; self-reported weekly frequency). Folic acid: intake ≥2 times/week for ≥1 month (ever use) or never (dosage not reported).
Results
Regular multivitamin supplement intake for ≥3 years is associated with a decreased CRC risk (HR 0.47; 95% CI 0.32–0.69). Regular calcium supplement intake for ≥3 years is associated with a decreased CRC risk (HR 0.42; 95% CI 0.23–0.74). Folic acid supplement intake shows no association with CRC risk (P = 0.82). Associations persisted across sexes and recruitment countries and after adjustment for confounders and screening; conclusion: multivitamin and calcium supplements might reduce CRC risk for carriers of pathogenic MMR gene mutations (Lynch syndrome).
Limitations
Observational design with self-reported supplement use; potential recall bias and measurement error; residual confounding from diet and lifestyle; lack of dosage information; possible immortality/survival bias and selection bias; generalizability limited to MMR gene mutation carriers; exposure data collected at recruitment; potential misclassification and unmeasured confounders.

Abstract

BACKGROUND People with a DNA mismatch repair (MMR) gene mutation have a substantially elevated risk of colorectal cancer (CRC) but the modifiers of this risk are not well established. We investigated the association between dietary supplement intake ...