Partial associations of dietary iron, smoking and intestinal bacteria with colorectal cancer risk

Abstract

Smoking and high red meat intake have been associated with colorectal cancer (CRC) risk. Increased iron exposure may be a common factor, favoring the colonization of certain bacterial pathogens that preferentially grow in an iron-rich luminal environment. We analyzed the data from a population-based case-control study of CRC and measured antibody levels against flagelin of Salmonella (FliC), one of the irontrophic bacteria, in 2 independent blood collections. The risk of CRC synergistically increased by combined exposures to heme iron intake and pack-yr (PY) of cigarette smoking (P value for the interaction = 0.039 on the continuous scale). There was a marginally significant interaction between heme iron intake and PY in increasing FliC antibody in the U.S. control subjects (P = 0.055), although no iron or smoking data were available for Dutch samples. Furthermore, FliC antibody levels were significantly higher in patients with colorectal polyps and cancer than in controls in both Dutch (3.93 vs. 2.23) (P = 0.014) and U.S. samples (6.65 vs. 4.37) (P < 0.001). Potential roles of iron from cigarette smoking and dietary heme in CRC through altering irontrophic luminal bacterial population may warrant further investigation.

Figure 1

Mean antibody titers to Salmonella flagellin and standard errors (SE) according to pack-years of cigarette smoking, dietary hem levels and their combinations in US control group (N=45). The numbers next to each bar indicate the mean titer and SE.

Figure 2

Mean antibody titers to Salmonella flagellin, their standard errors (SE), odds ratios (ORs) and 95% confidence intervals (CI) for colorectal tumors associated with above-median titer in each population (cutoff point= 2.00 for the Netherlands and 4.85 for US). The extended lines from the top of the bars indicate SEs and asterisks indicate statistical difference (P<0.05) from the controls.