Lung cancer mortality and serum levels of carotenoids, retinol, tocopherols, and folic acid in men and women: a case-control study nested in the JACC Study

J Epidemiol. 2005 Jun;15 Suppl 2(Suppl II):S140-9. doi: 10.2188/jea.15.s140.


Background: Lung cancer mortality is inversely associated with high serum carotenoid levels and high intake of vegetables and fruits rich in carotenoids. The Japan Collaborative Cohort (JACC) Study was conducted to investigate whether serum levels of carotenoids, retinol, tocopherols, and folic acid were associated with risk for lung cancer death with follow-up through 1997. To examine the association by sex, we extended the follow-up and analyzed additional serum samples.

Methods: In the JACC Study, 39,242 subjects provided serum samples at baseline between 1988 and 1990. We identified 211 cases (163 men and 48 women) of death from lung cancer during about 10-year follow-up ending in 1999. Of the subjects who survived to the end of that follow-up, 487 controls (375 men and 112 women) were selected, and were matched to each case of lung cancer death for sex, age and participating institution. We measured serum levels of antioxidants in cases of lung cancer death and controls. Odds ratio (OR) for lung cancer death was estimated using conditional logistic models by sex.

Results: For men, the risk of lung cancer death was significantly lower for the highest quartile of serum alpha- and beta-carotenes, lycopene, and beta-cryptoxanthin than for the lowest quartile: the OR adjusted for smoking and other covariates were 0.41, 0.28, 0.46, and 0.39, respectively. For women, serum levels of alpha-carotene and zeaxanthin/lutein were inversely associated with risk of lung cancer, but the association was not significant. No association between lung cancer and serum levels of beta-carotene, beta-cryptoxanthin, and retinol was appeared among women. There was a suggestion that association between lung cancer and high serum levels of these components might differ between men and women.

Conclusions: Higher serum levels of carotenoids appear to play a role in preventing death from lung cancer among Japanese men. Relationships between lung cancer and serum levels of some carotenoids appear to differ between sexes. However, further study with a large number of women cases needs to clarify the discrepancy between sexes.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antioxidants / administration & dosage
  • Antioxidants / analysis*
  • Carotenoids / administration & dosage
  • Carotenoids / blood*
  • Case-Control Studies
  • Cohort Studies
  • Female
  • Folic Acid / administration & dosage
  • Folic Acid / blood*
  • Humans
  • Japan / epidemiology
  • Lung Neoplasms / blood*
  • Lung Neoplasms / mortality*
  • Lung Neoplasms / prevention & control
  • Male
  • Middle Aged
  • Nutritional Status*
  • Sex Factors
  • Surveys and Questionnaires
  • Tocopherols / administration & dosage
  • Tocopherols / blood*
  • Vitamin A / administration & dosage
  • Vitamin A / blood*


  • Antioxidants
  • Vitamin A
  • Carotenoids
  • Folic Acid
  • Tocopherols