Moving Beyond Diet and Colorectal Cancer

Abstract

olorectal cancer (CRC) is third in incidence and mor- tality of all cancers worldwide, with rates parallel- ing economic development and a Westernized life- style (1,2). The majority of CRC cases occur sporadically, with environmental influences such as diet, exercise, al- cohol, and smoking viewed as risk factors. CRC is also associated with increasing age, with the majority of CRC cases diagnosed in individuals who are 60 years or older. CRC develops from precancerous lesions (adenomas or polyps) to malignant adenocarcinoma through genetic mutations altering the cell growth cycle (3). It is believed that it takes 10 to 15 years for an adenoma to develop into an adenocarcinoma, thus highlighting the importance of exposure and time for environmental factors. A recent review by the World Cancer Research Fund/American Institute for Cancer Research states that whereas there is convincing evidence that reduced physical activity, in- creased abdominal adiposity, and increased red meat and processed meat intakes increase CRC risk, evidence of the protective effects of fruits and nonstarchy vegetables on CRC risk is limited (4). Because tumor location (left vs right-sided cancers) is influenced by potential different biological pathways that may be responsible for carcino- genesis (5), studying fruit and vegetable (F/V) intake based on cancer subsites remains to be explored. earlier. Total and subgroups for F/V intakes were quan- tified as daily equivalent frequencies and divided into quartiles. Body mass index (BMI) was calculated from self-reported weight and height (as kg/m 2 ) at age 20 years. Individuals were categorized by diabetes and smoking status, physical activity level, and socioeconomic index. Case and control subjects were frequency matched on age and sex. Odds ratios and a test of trends were calculated across quartiles of F/V intakes, adjusting for covariates. In addition, analyses for all CRC cases were done based on tumor site. Differences between case and control subjects were found. Subjects with proximal cases of colon cancer were older and more likely to be female, whereas cases of rectal cancers were more likely to be male compared with con- trol subjects. Control subjects were also more likely to be underweight (at age 20) compared with all case (tumor site) groups. Participants with distal and rectal cancers drank 30 g more alcohol per day than control subjects. Case subjects also lived in lower socioeconomic regions than did control subjects. Multivariate modeling for overall CRC risk demon- strated no association between total F/V intake (together and separate), but when subgroups were analyzed, intake of apples (highest to lowest quartile) and dark-yellow vegetables (second, third quartiles compared to lowest) was significantly associated with a decreased CRC risk. In contrast, intake of fruit juice (highest to lowest quar- tile) was associated with an increased risk of CRC with significance for trend. When multinomial modeling was done to examine the risks by cancer site, the results seemed similar to the overall CRC risk. Intake of F/V was not associated with proximal colon cancer and rectal cancer risk. In addition, similar to the overall CRC models, intake of dark yellow vegetables (Q4 vs Q1, odds ratio (OR) 0.61 95% confi- dence interval (CI): 0.41 to 0.92) and apples (Q4 vs Q1, OR 0.51 95% CI: 0.34 to 0.77) were significant for a protective effect for distal colon cancers, and fruit juice (Q4 vs Q1, OR 1.74 95% CI: 1.24 to 2.45) was associated with an increased risk for rectal cancers. The exceptions in cancer site risks compared with overall CRC risk were that distal colon cancers exhibited a significance for a protective effect (Q4 vs Q1, OR 0.58 95% CI: 0.36 to 0.93) for total F/V intakes, and intake of brassica vegeta- bles was protective for proximal colon cancer risk (Q4 vs Q1, OR 0.62 95% CI: 0.41 to 0.93). These findings are similar to previous findings in meta- analyses in which weak or no associations were reported (4); however, the analysis by cancer site provides new information. Historically, nutritional epidemiology has relied on using the dietary intake model to assess cancer risk without accounting for other factors involved in the carcinogenesis pathway and also often used self-report for anthropometric data. Information on obesity-related