Association between Depression and Risk of Colorectal Cancer and Polyps: A Prospective Cohort Study from the Nurses' Health Study II.

BACKGROUND

Depression is a leading global health burden and has been linked to chronic diseases, including cancer. Chronic stress may promote colorectal carcinogenesis via hormonal, immune, and metabolic abnormalities. Evidence for the association between depression and colorectal cancer is inconsistent, and data on colorectal polyps are limited.

METHODS

We prospectively followed 91,383 women from the Nurses' Health Study II (1993-2019) for colorectal cancer analyses, and 62,237 women (1993-2017) for adenoma and serrated polyp analyses. Depression was defined as a Mental Health Index-5 score ≤52, antidepressant use, or physician-diagnosed depression. Multivariable Cox proportional hazards models estimated hazard ratios (HR) for colorectal cancer, whereas logistic regression estimated odds ratios (OR) for adenomas and serrated polyps.

RESULTS

Over 2.36 million person-years of follow-up, 474 colorectal cancer cases were documented. Depression was modestly associated with lower risk of colorectal cancer [HR = 0.76; 95% confidence interval (CI), 0.59-0.97] and colon cancer but not rectal cancer. Among 62,237 women undergoing lower endoscopy over 24 years, 4,104 conventional adenomas and 4,563 serrated polyps were documented. Depression was modestly inversely associated with overall and large conventional adenomas (OR = 0.76; 95% CI, 0.63-0.92). No consistent association was observed with serrated polyps in primary models, although some sensitivity analyses suggested possible positive associations.

CONCLUSIONS

Depression was inversely associated with colorectal cancer and large conventional adenomas. Associations with serrated polyps were not evident in primary models but varied across sensitivity analyses, requiring further study.

IMPACT: These findings suggest potential differences across colorectal neoplastic pathways, indicating that the relationship between depression and colorectal carcinogenesis may be more complex than previously appreciated.