Beta-cryptoxanthin and lung cancer in Shanghai, China--an examination of potential confounding with cigarette smoking using urinary cotinine as a biomarker for true tobacco exposure.

Diet may be a modifier of smoking-related cancer risk, with protective effects of intake of fruits and vegetables and associated antioxidants found in many observational studies. We previously reported serum beta-cryptoxanthin levels being inversely associated with smoking-related lung cancer incidence in a cohort of Chinese men. We noted, however, that serum beta-cryptoxanthin is negatively correlated with smoking. Since self-reports of smoking intensity undoubtedly contain errors, this negative correlation indicates a potential bias in assessing the effects of beta-cryptoxanthin, due to confounding with the unmeasured (residual) portion of cigarette exposure. We evaluated cotinine levels in pre-diagnostic spot urine samples to attempt to improve smoking assessment. We noted that urinary cotinine levels correlated significantly with cigarette consumption overall and that cotinine was strongly predictive of lung cancer risk. Urinary cotinine, however, was not as strong a predictor of lung cancer risk in current smokers as were self-reports of cigarette consumption and cotinine remained only a marginally significant predictor of lung cancer risk after adjustment for self-reports. An apparent benefit of beta-cryptoxanthin remained evident when including both urinary cotinine and self-reported cigarette consumption and cotinine in the statistical model. However, we conclude that cotinine measured from a single spot urine seems to have only limited value in augmenting self-reports of cigarette consumption so that, at present, the apparent protective effects of beta-cryptoxanthin, as seen in our own study, should continue to be regarded as unproven. We believe that future epidemiological evaluation of the association between beta-cryptoxanthin (and other antioxidants) and reduced lung cancer risk must utilize improved biomarkers to augment smokers' own self-reports of smoking amount.