Risk Factors for Rectal Neuroendocrine Tumors: A Population-Based Cohort Study of Sex-Specific Associations

Introduction: Risk factors for rectal neuroendocrine tumors (NETs) have rarely been reported in large-scale cohort studies, although previous cross-sectional research has reported some associations. We aimed to clarify the sex-specific contributing factors for rectal NETs.

We conducted a population-based cohort study, including individuals without previously diagnosed cancer and NETs who underwent national health examinations and cancer screenings in 2010, with follow-up until 2017.

Among 5.521 million, 2,342 patients with rectal NETs were identified. In the adjusted analysis, male sex (adjusted hazard ratio [aHR] 1.27; 95% confidence interval [CI]: 1.12-1.43), current smokers (aHR 1.15), past smokers (aHR 1.16), and obesity (aHR 1.50; 95% CI: 1.03-2.20) were significantly associated with elevated risk of rectal NETs. Frequent alcohol consumption was linked to rectal NETs in a dose-response relationship (aHR 1.37 for 1/week, 1.49 for 2-3/week, and 1.56 for 4-5/week). In men, current smokers, frequent alcohol intake, and obesity (HR 2.63; 95% CI: 1.44-4.80) were associated with elevated risk of NETs, while waist circumference also showed a significant trend (p for trend < 0.001). In women, past smokers (aHR 1.76) and alcohol intake were associated with rectal NETs. Younger age was a risk determinant in both men and women.

Younger age, smoking, and frequent alcohol intake were associated with increased rectal NET risk in both sexes. Obesity conferred a strong excess risk only in men but not in women. Due to observational study, causality cannot be inferred.