Dietary Factors: Assessment of Their Validity and Roles in Cancer Development and Progression

Abstract

The global burden of cancer is increasing, driven by population growth, aging, and lifestyle changes. In 2022, there were about 20 million new cases and 9.7 million deaths, and these numbers are projected to continue to rise. By 2050, over 35 million new cancer cases are expected a 77% increase from 2022. This increase in the number of cancer cases, together with improvements in cancer treatments, has also led to an increase in the number of people living with cancer. Consequently, there is an urgent need to reduce the cancer burden, with diet emerging as a key modifiable risk factor. Current knowledge on the relationship between diet and cancer has been significantly advanced by numerous well-designed studies over the past decade. The third edition of the World Cancer Research Fund (WCRF)/the American Institute for Cancer Research (AICR) reports provides a comprehensive synthesis of evidence regarding the role of diet in cancer prevention and survival. The report identifies several diet-cancer relationships with strong and convincing evidence. For example, high dietary fiber intake is associated with a reduced risk of colorectal cancer, while consumption of red and processed meats is linked to an increased risk of this cancer. However, the evidence for many diet-cancer links remains limited, often inconclusive. Optimizing research strategies to better characterize the diet-cancer relationship, particularly in terms of study design, dietary exposure assessment, and cancer outcomes, is therefore of paramount importance. This dissertation presents three studies that address challenges and limitations in diet and cancer research, with a focus on improving study design, validating dietary exposure assessments, and refining the evaluation of cancer outcomes. In Chapter 1, we explore the advantages of using a pooled study design to overcome the limitations inherent in individual studies, such as inadequate power and homogeneity of dietary behaviors. We investigated the associations between red and processed meat, poultry, seafood, and egg consumption and risk of Non-Hodgkin Lymphoma (NHL) and its histologic subtypes, using pooled data from 27 prospective cohort studies spanning four continents. Our study exemplifies the benefits of pooled analyses, particularly in the context of rare cancers and specific cancer subtypes. Additionally, it underscores the importance of analyzing diverse populations that enable study of specific subgroups of interest. In Chapter 2, we evaluate the reproducibility and validity of dietary exposure assessment, with a focus on overall diet quality. Overall diet quality reflects the synergistic and additive effects of various dietary components and is readily translatable into policy implications. We found food frequency questionnaires (FFQs) demonstrate strong validity in measuring several measures of diet quality. These findings demonstrate the feasibility in assessing diet quality in large-scale nutritional epidemiology research and support the future research studying the role of overall diet quality on cancer. In Chapter 3, we highlight the importance of studying cancer survival outcomes. While most diet and cancer studies focus on cancer prevention, there is a paucity of direct evidence supporting the dietary guidelines for cancer survivors. As such, we investigated the role of plant-based diets on survival following a breast cancer diagnosis and found that healthful dietary changes post-diagnosis can improve survival. This study highlights the need for further survival studies to strengthen and refine evidence-based dietary guidelines for cancer survivors.