Impact of Antioxidant Beta-carotenoid on Lung and Colorectal Cancer Mortality: An 18 Year Follow-up Study of A National Cohort Daneisha Hawkins, BS; Dr. Evans Afriyie-Gyawu, PhD, MPH; and Dr. Jian Zhang, MD, DrPH Department of Epidemiology and Environmental Health Sciences, Georgia Southern University

Introduction β-carotenoids, precursors of vitamin A, are important antioxidants within the physiological system in humans and animals Consumption of antioxidants containing fruits and vegetables is a part of overall healthy lifestyle Figure 1. Chemical structure of beta-carotene Figure 2: Examples of foods rich in β-carotene

Introduction continued… Lung cancer has been described to be the leading cause of cancer-related deaths in the U.S., followed by colorectal cancer (CDC, 2016) Decreased carotenoid levels are known to be directly associated with elevated markers of inflammation and oxidative stress Protective effects of β-carotenoids on individuals without cancer has been established; however, this effect has not been fully characterized among cancer patients

Objective & Hypothesis Objective: Examine the influence of serum β-carotenoid levels on lung and colorectal cancer mortality Hypothesis: Adequate physiological levels of serum β- carotenoid reduce lung and colorectal cancer mortality

Methods Study population: data were obtained from the NHANES III study using a multistage probability sampling of the noninstitutionalized US population (1988-1994) A retrospective cohort study conducted with 14,358 adults (19 years or older) who participated in phase II of the National Health and Nutrition Examination Survey III (1991-1994) (NHANES III) Data were collected via in-home interviews and visits by participants to a mobile examination center for blood sample collection

Methods Continued… Covariates such as family income, educational attainment, marital status, race/ethnicity, alcohol consumption, cigarette smoking, self-reported health status, body size, cancer status at baseline, vegetable/fruit/juice consumption were examined Serum samples were collected from study participants for the analysis. This served as baseline and was correlated with the National Death Index database between 1991-2006 Hazard ratio (HR) estimates for all-cause and cancer-related deaths among individuals with different serum β-carotenoid levels were obtained from Cox Proportional Hazards Regression

Results (Tables & Figures) Table 1. Adjusted vs. Unadjusted Hazard Ratio of Deaths Associated with Low Levels of Serum β-carotenoid (25% as cutoff) 14358 Adults2, NHANES III Follow-up Study 1988-2006 1 2 1Adjusted for age and sex 2Adjusted for age, sex, race, family income, educational attainment, alcohol consumption, cigarette smoking

Results (Tables & Figures) Table 2. Adjusted Hazard Ratio of Death Caused for ß-carotenoid Using 3-Level Categorization 1 1Adjusted for age, sex, race, family income, educational attainment, alcohol consumption, cigarette smoking

Results (Tables & Figures) cont’d… a) BCP3CAT and Lung Cancer Deaths (n=765) b) BCP3CAT and Colorectal Cancer Deaths (n=79) Blue = low levels of ß-Carotenoid, Red = high levels Green = moderate levels Fig 3: Survival functions of adults by the serum level of CAR3CAT, NHANES III follow-up, 1988-2006

Discussion Lung cancer is the leading type of cancer for men and women in the U.S, and colorectal cancer is third for both men and women in the U.S Results from this nationally representative study indicate that low serum ß-carotenoid levels are significantly associated with increased lung cancer mortality Association between high levels of serum ß-carotenoid and reduced risk of lung cancer mortality is biologically plausible Decreased carotenoid levels is associated with an elevation of inflammatory markers and oxidative stress which can enhance mortality among lung cancer patients

Strengths & Limitations To our knowledge, this is the first nationally representative study on U.S. population to examine the link between serum β-carotenoid and lung / colorectal cancer mortality. Due to the large sample size of this study, we were able to obtain informative risk estimates (Hazard Ratios) even when the data were adjusted for multiple covariates (potential confounders). We selected study participants from the community (extending beyond clinical populations) to achieve a true representation. Limitations: Data do not include the elderly in institutionalized facilities. Serum β-carotenoid level was measured only once during the study

Conclusions Our results indicate that low serum ß-carotenoid levels are significantly associated with risk of lung cancer mortality Findings from this study can be utilized to conduct further research on the effect(s) or benefits of carotenoids with respect to lung cancer mortality and determine optimum dose for intervention purposes It is essential to examine the effect(s) of the micronutrient ß- carotenoid on sensitive populations such as pregnant women, HIV/AIDS and other immunocompromised individuals

Conclusions continued… Public health officials may eventually use this information to increase fruit and vegetable consumption in order to reduce the risks associated with lung cancer mortality Further research is warranted to determine the mechanism by which optimum serum ß-carotenoid levels could extend survival among lung cancer patients

References Bouayed, J., & Bohn, T. (2010). Exogenous antioxidants—double- edged swords in cellular redox state: health beneficial effects at physiologic doses versus deleterious effects at high doses. Oxidative medicine and cellular longevity, 3(4), 228-237. CDC (2016). Colorectal Cancer Trends. Retrieved https://www.cdc.gov/cancer/colorectal/statistics/trends.htm CDC (2016b). Lung Cancer Trends. Retrieved from https://www.cdc.gov/cancer/lung/statistics/trends.htm Grune, T., Lietz, G., Palou, A., Ross, A. C., Stahl, W., Tang, G., ... & Biesalski, H. K. (2010). β-Carotene is an important vitamin A source for humans. The J of Nutr, 140(12), 2268S-2285S.

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