Colorectal Cancer Risk, Genetic Susceptibility and Night Shift Work in a Population-Based Case-Control Study in Spain

Abstract

Background and aims: Epidemiological studies on shift work have focused on breast cancer while evidence on other tumors is limited. We evaluated colorectal cancer risk in relation to shift work and genetic susceptibility in a population based case-control study in Spain (MCC-Spain study). Methods: 1066 male and 592 female incident colorectal cancer cases and 3388 randomly selected population controls in 11 regions of Spain were included. Information was collected on socio-demographic, lifestyle, medical history and other variables by face-to- face interviews. Lifetime occupational history on daily time schedules, day/night/rotating shifts shift-work intensity and duration of each job was examined. We used unconditional logistic regression analysis adjusting for potential confounders. We examined gene- environment interactions with genes in circadian rhythm pathways and melatonin metabolism testing simultaneously the main effect and the GxE interaction (2 d.f test). Results: Among controls 10% of males and 4% of females had ever worked full time in permanent night shifts (working between midnight and 6am) and 24% of males and 14% of females in rotating shifts for =1 year. Having ever performed rotating shift work was associated with an increased risk for colorectal cancer (adjusted Odds Ratio 1.33, 95%CI 1.15-1.55) compared to permanent day workers. ORs increased with cumulative years of rotating shift work and the OR for more than 30 years work was 1.54 (1.22-1.94). Having ever worked in permanent night shift was not associated with colorectal cancer risk. We observed nominal interactions between ever night shift work and several SNPs in circadian genes including PER2, TPH2, ARNTL2 although individual SNP associations did not remain statistically significant after Bonferroni correction. Conclusions: In this large population based study we found an increase in colorectal cancer risk in shift workers and an indication of interaction with genes in circadian pathways.