Vitamin D status and colorectal neoplasm risk in Lynch syndrome.

BACKGROUND

Higher circulating vitamin D concentrations have been associated with a decreased colorectal neoplasm (CRN) risk in the general population. However, this association has not yet been investigated in individuals with Lynch syndrome (LS), an inherited predisposition to colorectal cancer.

METHODS

The study population included 2,351 LS carriers from the GEOLynch and the Colon Cancer Family Registry cohorts. Total plasma 25-hydroxyvitamin D (25(OH)D2 and 25(OH)D3) concentrations were measured using isotope-dilution Liquid Chromatography-tandem Mass Spectrometry. CRNs included adenoma, serrated lesions, and colorectal cancer. Multivariable Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between 25-hydroxyvitamin D concentrations and CRN risk, overall and by pathogenic variant type, age, sex, CRN history and geographic region.

RESULTS

During a median follow-up of 7.2 years [IQR: 3.3-12.6], 647 (27.5%) LS carriers developed a CRN. No association was observed for deficient (<50 nmol/L or <20 ng/mL; HR: 1.12; 95% CI: 0.91, 1.39) or optimal (≥75 nmol/L or ≥30 ng/mL; HR: 0.94; 95% CI: 0.77, 1.15) compared with sufficient (50-<75 nmol/L or 20-<30 ng/mL) vitamin D concentrations. No association was observed for each 10 nmol/L or 4 ng/mL increment in vitamin D concentration. Among PMS2 carriers, a 10 nmol/L increment was associated with a 27% lower CRN risk (HR: 0.73; 95% CI: 0.58-0.91).

CONCLUSIONS

Vitamin D concentrations were not associated with CRN risk among LS carriers, whereas the association observed among PMS2 carriers warrants further investigation.

IMPACT: If confirmed, these findings could inform personalized risk reduction strategies for PMS2 carriers.