Pre-adult famine exposure and subsequent colorectal cancer risk in women

Abstract

Background: Nutritional deprivation during growth and development may contribute to colorectal cancer (CRC) risk in later life.

Methods: We studied 7906 women who were aged 0-21 years during the 1944-45 Dutch famine, who enrolled in the Prospect-EPIC study between 1993 and 1997. We used Cox proportional hazard analyses to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for colorectal (proximal, distal and rectal) cancer risk across self-reported famine exposure and exposure-age categories, while adjusting for potential confounders.

Results: During a median of 17.3 years of follow-up, 245 CRC cases occurred. Moderately and severely famine-exposed women showed a respective 24% and 44% higher CRC risk compared with women who reported no exposure [HR moderate 1.24 (95% CI: 0.93-1.64); HR severe 1.44 (1.03-2.03); P trend 0.027]. This relation attenuated when adjusted for potential confounders [adjusted HR moderate 1.15 (0.87-1.53); HR severe 1.35 (0.96-1.90); P trend 0.091]. Stratified results suggested that severe famine exposure between 10 and 17 years of age was particularly related to CRC risk[adjusted HR moderate 1.39 (0.91-2.11); HR severe 1.76 (1.10-2.83); P trend 0.019; P interaction(famine*10-17yrs) 0.096]. Overall, we found no differences in famine effects across CRC subsites, but age-at-exposure stratified results suggested an increased risk for proximal CRC in those aged 10-17 years during exposure to the famine [adjusted HR moderate 2.14 (1.06-4.32), HR severe 2.96 (1.35-6.46); P trend 0.005]. Overall and within age-at-exposure categories, tests for subsite specific heterogeneity in famine effects were not significant.

Conclusions: Our findings suggest that severe exposure to a short period of caloric restriction in pre-adult women may relate to CRC risk decades later.

Keywords: Colorectal cancer; adolescence; caloric restriction; cohort studies; famine; growth and development; metabolism; starvation; vulnerable periods.