Dietary, Lifestyle, and Genetic Factors Influencing Colorectal Cancer Risk
Open Access
- Author:
- Ashmore, Joseph Henderson
- Graduate Program:
- Nutrition
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- January 28, 2013
- Committee Members:
- Terryl Johnson Hartman, Dissertation Advisor/Co-Advisor
Terryl Johnson Hartman, Committee Chair/Co-Chair
Connie Jo Rogers, Committee Member
Shannon Leanne Kelleher, Committee Member
Arthur Steven Berg, Committee Member
Samuel M Lesko, Committee Member - Keywords:
- Colorectal cancer
nutrition
genetics - Abstract:
- Cancers of the colon and rectum (colorectum) are complex diseases that form through a combination of both intrinsic (e.g. genetic variation) and extrinsic (e.g. environmental) factors. Currently, colorectal cancer (CRC) is the second leading cancer killer in the United States and the fourth most common form of cancer diagnosed. Many epidemiologic and laboratory studies have found that food and nutrition play an important role in both the incidence and progression of colorectal cancers. Data for the following studies were collected from adult men and women in central and northeastern Pennsylvania, which has higher CRC incidence and mortality rates than the United States average. Cases were identified from the Pennsylvania cancer registry and population-based controls were identified via random-digit dialing. Dietary information was collected via a modified Diet History Questionnaire (DHQ) developed by Subar and colleagues at the National Cancer Institute (NCI) including supplement use and an additional meat module. Sociodemographic, lifestyle, and buccal cells for genomic DNA analysis were collected during in-person interviews. The objective of the first study was to examine colorectal cancer risk associated with iron intake (total, dietary, supplemental, and heme). Heme iron content from the diet was calculated using a new heme iron database developed by the NCI using information from a detailed meat module that was added to the food frequency questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression. After multivariate adjustment, there were no significant associations between heme iron or total iron intake and CRC incidence. Dietary iron was inversely associated with colorectal cancer risk in women (OR Q5 vs. Q1¬= 0.45; 95% CI = 0.22-0.92), but not men. Lastly, supplemental iron intake of >18 mg/d vs. none was positively associated with colorectal cancer risk (OR = 2.31; 95% CI = 1.48-3.59; P-trend <0.001). In summary, these findings suggest that consumption of >18 mg/d of supplemental iron may increase risk for colorectal cancer. In the second study, our objective was to examine the associations between calcium and vitamin D intake (total, dietary, and supplemental) and incident colorectal cancer. We found an inverse association between total vitamin D intake and colorectal cancer risk (OR = 0.67; 95% CI = 0.49-0.91; P-trend < 0.01). Higher levels of total calcium intake were also inversely associated with colorectal cancer incidence (OR Q5 v. Q1= 0.48; 95% CI = 0.35-0.66; P-trend <0.01). In addition, high supplemental intakes of vitamin D (>10 μg/d) and calcium (>500 mg/d) were associated with reduced risk (OR High v. None = 0.68; 95% CI = 0.53-0.89, P-trend = 0.05; OR High v. None = 0.61; 95% CI = 0.46-0.81, P-trend < 0.01, respectively). Overall, our results indicate reduced risk of colorectal cancer with higher total and supplemental intakes of vitamin D and calcium. In our final study, we examined the associations between folate intake (total, dietary, and supplemental) and incident colorectal cancer. We also assessed the impact of 35 polymorphisms from three folate-mediated one-carbon metabolism (FOCM)-related genes on colorectal cancer risk. Finally, we examined whether there were any gene-diet interactions between folate intake and FOCM-related polymorphisms that alter colorectal cancer risk within the present multi-site population-based case-control study. After multivariate adjustment, colorectal cancer risk was not significantly associated with dietary or supplemental folate intake overall. Four polymorphisms from three genes had significant interactions with dietary intake factors associated with colorectal cancer risk. Significant associations were also observed among five polymorphisms related to FOCM. In conclusion, our results suggest that allelic variants in genes involved in FOCM, coupled with dietary intakes modify risk for colorectal cancer. In conclusion, our research shows several micronutrients may alter colorectal cancer risk. Our research also indicates several polymorphisms that may alter cancer risk and provides a solid foundation for future studies investigating gene-environment interactions.