A priori diet quality indices and cancer-related outcomes in newly diagnosed head and neck squamous cell carcinoma survivor

Maino Vieytes, Christian Augusto

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https://hdl.handle.net/2142/120537 Copy

Description

Title

A priori diet quality indices and cancer-related outcomes in newly diagnosed head and neck squamous cell carcinoma survivor

Author(s)

Maino Vieytes, Christian Augusto

Issue Date

2023-04-26

Director of Research (if dissertation) or Advisor (if thesis)

Arthur, Anna E

Doctoral Committee Chair(s)

Madak-Erdogan, Zeynep

Committee Member(s)

• Smith, Rebecca L
• Rodriguez-Zas, Sandra L

Department of Study

Nutritional Sciences

Discipline

Nutritional Sciences

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• nutritional epidemiology
• dietary patterns
• cancer survivorship
• cancer
• diet quality
• marginal structural models
• epidemiology

Abstract

The analysis of dietary patterns in epidemiological studies is fundamental for summarizing dietary behaviors in populations and ascertaining associations between diet and chronic illness. Methods for characterizing dietary patterns in population studies are broadly categorized into a posteriori, and a priori approaches. Such approaches are essential for understanding prevailing dietary patterns in populations and informing the development of guidelines and policies that make dietary recommendations for curtailing the incidence and exacerbation of diseases. Within the head and neck squamous cell carcinoma (HNSCC) survivor population, there is an urgent need to clarify dietary and lifestyle factors that influence survivorship. HNSCC is a heterogenous class of cancers impacting the upper aerodigestive tract linked primarily to smoking and drinking behaviors and infection with human papillomavirus-16 (HPV-16). HNSCC prognosis remains low, and survivorship is associated with a bounty of dietary and nutrition-related challenges. Evidence from epidemiological studies suggests that dietary factors influence the risk of developing HNSCC. In particular, the consumption of dietary fiber has been demonstrated as a protective factor in females but not males. Fruit and vegetable consumption has also been identified as a protective behavior, although these associations are modified by HPV-16 serological status. Concerning the associations between dietary variables and cancer-related outcomes following a HNSCC diagnosis, some evidence suggests enhanced prognosis with the consumption of certain nutrients. However, most of this evidence comes from case-control or cross-sectional studies and focuses primarily on single nutrients rather than dietary patterns. The work out of our research team has elucidated several dietary factors associated with improved outcomes in the University of Michigan Head and Neck Specialized Program of Research Excellence (SPORE) longitudinal survival cohort study. However, to our knowledge, no published studies highlight how a priori-defined diet quality indices affect survivorship outcomes in HNSCC. The primary goal of the research presented in this dissertation was to identify a priori-defined diet quality indices that improved survival and recurrence and identify how those dietary patterns impacted biomarkers in newly diagnosed HNSCC survivors enrolled in the SPORE longitudinal cohort study. A secondary goal of this dissertation was to review methods and modeling approaches in nutritional epidemiology and causal inference spaces to inform the subsequent analyses conducted. These analyses used longitudinal and nested cross-sectional and case-control data from the University of Michigan SPORE longitudinal cohort study to answer the research questions in the specific aims. The first specific aim of this dissertation investigated the relationships between dietary fiber intake and intake of whole grains, measured at pretreatment, and the risks of mortality and recurrence in 463 HNSCC survivors from the SPORE dataset. Food frequency questionnaires were administered at pretreatment to quantify dietary intake and estimate daily intakes of dietary fiber and whole grains (both in grams). Time-to-death and time-to-recurrence were monitored for study subjects throughout the study period by consulting numerous sources, including medical record reviews, the Social Security Death Index, and cancer registries. We modeled the dietary exposure variables using various methods, including categorization, a test for trend, and restricted cubic splines. Cox proportional hazards models were fit to the data to estimate hazard ratios (HRs) and 95% confidence intervals. During the study period, there were 121 deaths and 112 documented recurrences. Dietary fiber intake at pretreatment was inversely associated with the risk of all-cause mortality (HRQ5−Q1: 0.37, 95% CI: 0.14–0.95, ptrend = 0.04). There were no significant associations between whole grains intake and mortality. Moreover, there were no significant associations between dietary fiber, whole grains intake, and cancer recurrence. Finally, there was no evidence of effect modification reported in this study. The second specific aim of this dissertation investigated the relationships between six a priori¬-defined diet quality indices and all-cause and cancer-specific mortalities in 468 newly diagnosed HNSCC patients from the SPORE cohort. Unlike the previous specific aim, this analysis considered and evaluated associations using dietary intake at three study visits: pretreatment, one-year post-treatment, and two years post-treatment. The diet quality indices included the Alternative Healthy Eating Index 2010 (AHEI-2010), the Alternate Mediterranean Diet Index (aMED), the Dietary Approaches to Stop Hypertension (DASH), and three low-carbohydrate indices (an overall low-carbohydrate index, an animal-foods based low-carbohydrate index, and a plant-foods based low-carbohydrate index). These indices were computed using the data estimated from the FFQ described above, administered at the three study visits. To mitigate the potential for time-varying confounding, as a result of using time-updated measures of these diet indices, an approach involving marginal structural models and inverse probability of treatment weighting (IPTW) was adopted. Time-varying Cox regression models were used to evaluate the relationship between adherence to the diet quality indices throughout the first three years of follow-up and the risks of all-cause and cancer-specific mortality. Numerous model specifications were used to assess the robustness of the results. There were 93 deaths from all causes and 74 cancer-related deaths reported in this study period. Adherence to the AHEI-2010 was strongly and inversely associated with all-cause mortality (HRQ5−Q1: 0.07, 95% CI: 0.01–0.43, ptrend = 0.04) and cancer-specific mortality (HRQ5−Q1: 0.15, 95% CI: 0.02–1.07, ptrend = 0.04). There were associations between other a priori diet quality indices and the outcomes. Albeit, these results were more modest and not as robust as those involving the AHEI-2010. In Specific Aim 3A of this dissertation, we investigated the relationship between dietary intake and oral microbiome in a nested case-control study of HNSCC participants from the SPORE cohort study. Controls were recruited through the University of Michigan Hospital System and the community and matched to cases on age and gender. The dietary exposure variables of interest in this analysis were the six a priori diet quality indices examined in the second specific aim and 32 food group categories. Oral microbiome DNA samples were obtained through oral washes and sequenced by amplifying the V4 region of 16S rRNA gene. The primary outcomes of this analysis were α and β diversity metrics and the relative abundances of operational taxonomic units (OTUs). We employed three α diversity metrics (Shannon, Chao1, and Simpson) to evaluate species richness and diversity according to the dietary variables. We used Permutational Multivariate Analysis of Variance (PERMANOVA) to evaluate compositional differences, using Bray Curtis distances, across tertiles of the diet quality indices. All analyses were performed separately in cases and controls to assess for effect modification. There were no appreciable or significant results relating diet quality, as measured by the a priori diet quality indices, to species richness nor overall composition in either cases or controls. Some significant results suggested associations between certain food groups and OTUs and were modified by case and control status. However, it was apparent that a small handful of observations drove those associations. In Specific Aim 3B of this dissertation, we investigated the relationship between the six a priori-defined diet quality indices, measured only at pretreatment, and levels of proinflammatory cytokines measured in serum samples from newly diagnosed HNSCC participants in the SPORE longitudinal cohort study. Venous blood samples were obtained, and the sera were collected and stored for analysis of a panel of ten proinflammatory cytokines [Interleukin (IL)-6, IL-8, IL-10, IL-17, Growth-Related-Oncogene (GRO)-β, Hepatocyte Growth Factor (HGF), Interferon-γ (IFN-γ), Transforming Growth Factor (TGF)-β, Tumor Necrosis Factor-α, and Vascular Endothelial Growth Factor (VEGF)]. Proportional odds and logistic regression models were used to assess the relationships between the a priori diet quality indices and the odds of having high levels of proinflammatory cytokines. Models were fit for each different cytokine, and a cytokine composite summary measure was also generated to globally evaluate the link between diet and systemic inflammation in this subset of participants. There were several inverse associations between the AHEI-2010, individual cytokine levels, and the global composite summary measure of inflammation (ORQ4−Q1(Prop. Odds): 3.38, 95% CI: 1.28–8.92, ptrend < 0.01). Relationships between other a priori indices and proinflammatory cytokine levels were investigated, but they were not as strong nor consistent. In summary, adhering closely to a diet that follows the tenets prescribed by the AHEI-2010 was associated with improved survival in a longitudinal cohort study of subjects with newly diagnosed HNSCC. These results were substantiated by findings demonstrating a set of strong inverse associations between AHEI-2010 adherence and levels of proinflammatory cytokines. Future research investigating dietary interventions or protocols that score highly on the AHEI-2010 index is warranted. Furthermore, future efforts should also focus on developing a HNSCC-specific diet quality index that draws from the AHEI-2010. Finally, these results should inform clinicians and health care professionals in their dietary counseling of patients with HNSCC.

Graduation Semester

2023-05

Type of Resource

Thesis

Copyright and License Information

Copyright 2023 Christian Maino Vieytes

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