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

Dept. of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT (S.T.M., B.C., H.L., T.Z.)
University of Miami, Miami, FL (W.J.G.)

Address correspondence to: Susan T. Mayne, Ph.D., Yale University School of Medicine, Department of Epidemiology and Public Health, 60 College St., P.O. Box 208034, New Haven, CT 06520-8034 E-mail: susan.mayne{at}yale.edu

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.

Key words: lycopene, carotenoids, mortality, prospective study, beta-carotene, human

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