Low Plasma Lycopene Concentration is Associated with Increased Mortality in a Cohort of Patients with Prior Oral, Pharynx or Larynx Cancers

OBJECTIVE: This analysis was conducted to evaluate the association between plasma beta-carotene, alpha-carotene, lycopene, lutein/zeaxanthin, total carotenoids, retinol, alpha-tocopherol and subsequent mortality. METHODS: Blood samples collected longitudinally from 259 participants in a chemoprevention trial aimed at the prevention of second cancers of the oral cavity, pharynx, or larynx were analyzed by high performance liquid chromatography for selected micronutrients. All-cause mortality (primary outcome) and cause-specific mortality (secondary outcomes) were evaluated in relation to plasma micronutrient concentrations at baseline and longitudinally. RESULTS: A total of 61 deaths occurred over a follow-up time of up to 90 months. Cox proportional hazards models with time-dependent covariates were used for data analyses. In models adjusted for age, plasma cholesterol, time-dependent smoking, treatment arm, study site and gender, only plasma lycopene was significantly inversely associated with total mortality [hazard ratio (HR) above versus below median = 0.53, 95% confidence interval (CI) 0.30-0.93]. Plasma alpha-carotene was inversely associated (HR 0.24, 95% CI 0.08-0.75) while plasma retinol was positively associated (HR 5.12, 95% CI 1.54-17.05) with cardiovascular death. Smoking status modified plasma nutrient associations with total mortality. Lycopene (HR 0.08, 95% CI 0.02-0.36), alpha-carotene (HR 0.25, 95% CI 0.09-0.73) and total carotenoids (HR 0.22, 95% CI 0.07-0.70) were inversely associated with mortality in non-smokers, while plasma retinol (HR = 3.56, 95% CI 1.40-9.09) and alpha-tocopherol (HR = 2.47, 95% CI 1.02-5.98) were positively associated with mortality in smokers. CONCLUSIONS: Only plasma lycopene was significantly associated (inversely) with total mortality in the full study population. Smoking modifies associations between nutrients and mortality.