ONLINE PERSPECTIVE

CORRESPONDENCE

Re: {beta}-Carotene and Lung Cancer: A Lesson for Future Chemoprevention Investigations?

Daniel O. Stram, Anna H. Wu

Affiliation of authors: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA.

Correspondence to: Daniel Stram, Ph.D., Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033 (e-mail: stram{at}usc.edu).

Peter Greenwald’s review (1) of the issues surrounding the {alpha}-Tocopherol, {beta}-Carotene Cancer Prevention (ATBC) Study and {beta}-Carotene and the Retinol Efficacy Trial (CARET) mentions a number of possible reasons why the results of these trials differed from the many epidemiologic observations showing an association between reduced lung cancer risk and higher fruit and vegetable intake (2) and higher serum {beta}-carotene (3). One of the important observations that led to these trials was the prospective finding (4) that smokers with higher measurements of serum {beta}-carotene had, in follow-up (up to 9 years), a statistically significantly reduced risk of lung cancer, whereas less consistent associations were observed with other micronutrients associated with fruit and vegetable intake. Also evident in such data, however, was an inverse relationship between the levels of serum {beta}-carotene and both smoking status and the number of cigarettes smoked per day (5). There is now evidence that exposure to tobacco has a direct biochemical effect on serum levels of {beta}-carotene (6). Because smoking causes the large majority of lung cancer cases, it is possible that the observed association between serum {beta}-carotene and lung cancer was largely the result of residual confounding with imperfectly reported tobacco exposure—that is, that levels of {beta}-carotene simply served as a biomarker for true smoking level. We believe that this explanation can hold, however, only if self-reported smoking (i.e., number of cigarettes smoked per day, for current smokers) is actually poorly correlated (R < 0.6) with the relevant true components of smoking that directly cause lung cancer (7). If correlations between self-report and biologically relevant tobacco exposure are truly this low, then future observational studies (e.g., of other antioxidants) are at risk of producing false positive results due to residual confounding with the unmeasured portion of true exposure.

Therefore, we consider it of importance to better understand the strength of the relationship between self-reports of smoking level and the actual exposure to biologically relevant components of tobacco. It is also important to further develop and use biomarkers for biologically relevant dose to supplement smoking self-reports in future epidemiologic investigations of lung cancer.

REFERENCES

1 Greenwald P. Beta-Carotene and lung cancer: a lesson for future chemoprevention investigations? J Natl Cancer Inst 2003;95:E1.[Free Full Text]

2 Block G, Patterson B, Subar A. Fruit, vegetables, and cancer prevention: a review of the epidemiological evidence. Nutr Cancer 1992;18:1–29.[Medline]

3 van Poppel G, Goldbohm RA. Epidemiologic evidence for beta-carotene and cancer prevention. Am J Clin Nutr 1995;62:1393S–1402S.[Abstract]

4 Menkes MS, Comstock GW, Vuilleumier JP, Helsing KJ, Rider AA, Brookmeyer R. Serum beta-carotene, vitamins A and E, selenium, and the risk of lung cancer. N Engl J Med 1986;315:1250–4.[Abstract]

5 Stryker WS, Kaplan LA, Stein EA, Stampfer MJ, Sober A, Willett WC. The relation of diet, cigarette smoking, and alcohol consumption to plasma beta-carotene and alpha-tocopherol levels. Am J Epidemiol 1988;127:283–296.[Abstract]

6 Handelman GJ, Packer L, Cross CE. Destruction of tocopherols, carotenoids, and retinol in human plasma by cigarette smoke. Am J Clin Nutr 1996;63:559–65.[Abstract]

7 Stram DO, Huberman M, Wu AH. Is residual confounding a reasonable explanation for the apparent protective effects of beta-carotene found in epidemiological studies of lung cancer in smokers? Am J Epidemiol 2002;155:622–8.[Abstract/Free Full Text]



             
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