Genetic variability of the forkhead box O3 and prostate cancer risk in the European Prospective Investigation on Cancer.
Campa D., Hüsing A., Dostal L., Stein A., Drogan D., Boeing H., Tjønneland A., Roswall N., Østergaard JN., Overvad K., Rodríguez L., Bonet C., Sánchez M-J., Larrañaga N., Huerta JM., Ardanaz E., Khaw K-T., Wareham N., Travis RC., Allen NE., Trichopoulou A., Zylis D., Karapetyan T., Palli D., Sieri S., Tumino R., Vineis P., Bueno-de-Mesquita HB., Lenner P., Johansson M., Jenab M., Cox D., Siddiq A., Kaaks R., Canzian F.
Forkhead box O3 (FOXO3) has a wide range of functions: it promotes tumor suppression, cell cycle arrest, repair of damaged DNA, detoxification of reactive oxygen species, apoptosis and plays a pivotal role in promoting longevity. FOXO3 is a key downstream target of the PI3K-Akt pathway in response to cellular stimulation by growth factors or insulin and has been proposed as a bridge between ageing and tumor suppression. Three SNPs in the FOXO3 gene (rs3800231, rs9400239 and rs479744) that have been shown to be strongly and consistently associated with longevity, were examined in relation to PC risk in a case control study of 1571 incident PC cases and 1840 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). There was no statistically significant association between the SNPs and PC risk regardless of the model of inheritance (dominant, codominant and recessive). The associations were not modified by disease aggressiveness, circulating levels of steroid sex hormones, or IGFs or BMI. We conclude that polymorphisms in the FOXO3 gene that are associated with longevity are not major risk factors for PC risk, in this population of Caucasian men.