Prediagnostic levels of serum beta-cryptoxanthin and retinol predict smoking-related lung cancer risk in Shanghai, China

Higher blood levels of beta -carotene have been found to be associated with reduced risk of lung cancer, but large intervention trials have failed to demonstrate reduced lung cancer incidence after prolonged high dose beta -c arotene supplementation. Data on blood levels of specific carotenoids other than beta -carotene in relation to lung cancer are scarce. Little is known about the relationship between prediagnostic serum levels of carotenoids, retinol, and tocopherols, and risk of lung cancer especially in non-Western populations. Between January 1986 and September 1989, 18,244 men ages 4564 years participated in a prospective study of diet and cancer in Shanghai, China. Information on tobacco smoking and other lifestyle factors was obtai ned through in-person interviews. A serum sample was collected from each st udy participant at baseline. During the first 12 years of follow-up, 209 lu ng cancer cases, excluding those diagnosed within 2 years of enrollment, we re identified. For each cancer case, three cancer-free control subjects wer e randomly selected from the cohort and matched to the index case by age (w ithin 2 years), month and year of blood sample collection, and neighborhood of residence. Serum concentrations of retinol, alpha- and gamma -tocophero ls, and specific carotenoids including alpha -carotene, beta -carotene, bet a -cryptoxanthin, lycopene, and lutein/zeaxanthin were determined on the 20 9 cases and 622 matched controls by high-performance liquid chromatography methods. A high prediagnostic serum level of beta -cryptoxanthin was signif icantly associated with reduced risk of lung cancer; relative to the lowest quartile, the smoking-adjusted relative risks (95% confidence intervals) f or the 2nd, 3rd, and 4th quartile categories were 0.72 (0.41-1.26), 0.42 (0 .21-0.84), and 0.45 (0.22-0.92), respectively (P for trend = 0,02). Increas ed serum levels of other specific carotenoids including alpha -carotene, be ta -carotene, lycopene, and lutein/zeaxanthin were related to reduced risk of lung cancer although the inverse associations were no longer statistical ly significant after adjustment for smoking. A statistically significant 37 % reduction in risk of lung cancer was noted in smokers with above versus b elow median level of total carotenoids. Serum retinol levels showed a thres hold effect on lung cancer risk. Compared with the lowest quartile (<40 <mu >g/dl), the smoking-adjusted relative risk (95% confidence interval) was 0. 60 (0.39-0.92) for men in the 2nd-4th quartiles of retinol values combined; no additional decrease in risk was observed between individuals from the 2 nd to 4th quartiles. There were no associations between prediagnostic serum levels of (alpha- and gamma -tocopherols and lung cancer tall Ps for trend greater than or equal to0.4). The present data indicate that higher predia gnostic serum levels of total carotenoids and beta -cryptoxanthin were asso ciated with lower smoking related lung cancer risk in middle-aged and older men in Shanghai, China. Low level of serum retinol (with a threshold effec t) is associated with increased lung cancer risk in this oriental populatio n.