Open Access
Miller, Paige Elizabeth
Graduate Program:
Doctor of Philosophy
Document Type:
Date of Defense:
March 22, 2010
Committee Members:
  • Terryl Johnson Hartman, Dissertation Advisor
  • Terryl Johnson Hartman, Committee Chair
  • Leann L Birch, Committee Member
  • Penny Margaret Kris Etherton, Committee Member
  • David Theodore Mauger, Committee Member
  • Philip Lazarus, Committee Member
  • heterocyclic amines
  • meat
  • nutrition
  • diet
  • rectal cancer
  • polycyclic aromatic hydrocarbons
  • colon cancer
  • nitrosamines
Colorectal cancer is the fourth most commonly diagnosed malignancy in developed countries and the second leading cause of cancer death in the U.S. A recent consensus report issued by the World Cancer Research Fund and the American Institute for Cancer Research concluded that the evidence to support a positive association between greater intakes of red and processed meat and colorectal cancer risk was convincing, although the specific components within meat driving these associations remained unclear. The report also stated that there was insufficient evidence to render judgment regarding dietary patterns and colorectal cancer risk. To address these identified gaps in knowledge, we explored associations between both dietary patterns and specific meat components and colorectal cancer risk in a large multi-site population-based case-control study in a high-risk adult population in northeast and central Pennsylvania. Participants completed a 137-item food frequency questionnaire that included a detailed cooked and processed meat module, which allowed for the use of databases of heterocyclic amines (HCAs), polycyclic aromatic hydrocarbons (PAHs), nitrites, and nitrates. In the first study, our objective was to examine colorectal cancer risk associated with dietary patterns among 431 incident cases (225 men, 206 women) and 726 healthy controls (330 men, 396 women). The majority of previous studies have derived patterns either by measuring compliance with pre-established dietary guidance or by empirical methods such as principal components analysis (PCA). We explored whether dietary patterns identified by both methods were associated with colorectal cancer risk. Three dietary patterns among men (fruits and vegetables, meat and potatoes, alcohol and sweetened beverages) and two among women (fruits and vegetables, meat and potatoes) were identified by PCA. Healthy Eating Index-2005 (HEI-05) scores were generated to assess the degree of adherence to recommendations found in the Dietary Guidelines for Americans. After adjusting for potential confounders, the PCA-derived fruits and vegetables pattern was inversely associated with colorectal cancer risk among both men (odds ratio (OR) = 0.38, 95% confidence interval (CI) = 0.21-0.69 for the highest compared to the lowest quartile; P for trend = 0.006) and women (OR = 0.35, 95% CI = 0.19-0.65; P for trend = 0.031). In contrast, the meat and potatoes pattern was positively associated with risk in women (OR = 2.20, 95% CI = 1.08-4.50; P for trend = 0.070) and there was a suggestion of a positive association among men (OR = 1.56, 95% CI = 0.84-2.90; P for trend = 0.070). Men and women with greater HEI-05 scores had a significant reduction in risk (OR = 0.56, 95% CI = 0.31-0.99; P for trend = 0.004; OR = 0.44, 95% CI = 0.24-0.77; P for trend <0.001, respectively). In summary, findings from the first study indicate that both the hypothesis-oriented diet index-based approach and the empirically-driven PCA approach are of value in the study of diet and colorectal cancer associations and that following the Dietary Guidelines or a primarily plant-based dietary pattern that includes low-fat dairy and fish may be protective. In the second study, our objective was to explore potential underlying mechanisms for previously observed associations between red and processed meat and colorectal cancer risk. We examined whether increased levels of exposure to mutagens generated through meat cooking and meat processing methods were risk factors for colon and rectal cancer among 726 healthy controls, 287 colon cancer cases, and 128 rectal cancer cases. Associations between meat exposures and colorectal cancer stratified by sub-site of the large intestine were estimated from unconditional logistic regression models. After multivariate adjustment, positive associations with HCAs and PAHs, as measured by total mutagenic activity, were stronger for rectal cancer (OR = 1.75, 95% CI = 1.00, 3.08; P for trend = 0.031) than colon cancer, whereas suggestive positive associations with nitrites plus nitrates were stronger for colon cancer (OR = 1.28, 95% CI = 0.82-2.00; P for trend = 0.084). These findings support the hypothesis that greater exposure to HCAs, PAHs, nitrites, and nitrates is a plausible mechanism by which red and processed meat may increase colorectal cancer risk. Our sub-site analyses indicate that associations between meat-derived exposures and colon and rectal cancer may differ, which underscores the need for additional studies that examine dietary risk factors for colon and rectal cancer as separate endpoints. In conclusion, our research supports the complementary study of both dietary patterns and individual dietary components as cancer risk factors as each can serve a unique purpose in identifying areas to target for colorectal cancer prevention strategies as well as future research studies.