Long-term use of lithium and risk of colorectal adenocarcinoma: a nationwide case–control study

BACKGROUND: Lithium accumulates in the colon and inhibits the enzyme GSK-3β that possesses anti-carcinogenic effects. We therefore examined the association between lithium use and colorectal cancer risk in a nationwide study. METHODS: We used the Danish Cancer Registry to identify all patients diagnosed with incident colorectal adenocarcinoma during 2000–2012 (n=36 248). Using a matched case–control approach, we estimated the association between long-term use (⩾5 years) of lithium and risk of colorectal adenocarcinoma using conditional logistic regression. RESULTS: Long-term use of lithium was similar among cases (0.22%) and controls (0.20%), yielding an odds ratio of 1.13 (95% confidence interval (CI), 0.89–1.43) for colorectal adenocarcinoma. Dose–response, subgroup and other subanalyses returned neutral associations. However, ORs differed for colorectal subsites (proximal colon: 1.01 (95% CI, 0.66–1.55; distal colon: 1.52 (95% CI, 1.05–2.20); and rectum: 0.80 (95% CI, 0.50–1.30). CONCLUSIONS: Lithium use was not associated with an overall increased risk of colorectal adenocarcinoma. The variation by subsite warrants further investigation.