Transferrin C3 offers protection against smoking-associated lung cancer?

In previous investigations increased body iron stores and transferrin (TF) variants have been found to be associated with adverse health effects, including cancer. In this investigation transferrin C (TF C) subtypes were studied in lung cancer patients and controls from the Stockholm area in central Sweden. There was a significant difference between patients and controls with respect to the distribution of TF C alleles and genotypes, which was mainly due to a low frequency of the TF C3 allele among the patients (P = 3 x 10(-6). However, in adenocarcinoma the frequency of TF C3 types was almost identical to that among the controls, whereas in the smoking-related (squamous and small cell) tumor types the TF C3 frequency was remarkably low (OR = 0.03, 95% CI = 0.00-0.22). Thus individuals with the TF C3 variant appear to enjoy an almost complete protection against smoking-related lung cancer. The frequency of individuals carrying the protective TF C3 variant is approximately 17% in central Sweden and 25% in Finland, which has the highest TF C3 frequency found so far. The mechanism behind the observed association, which appears to be independent of iron binding and body iron stores, remains to be elucidated.