mozygous for Tyrll3. ORs of lung cancer and 95% CIs in relation to EPHX polymorphisms and to predicted mEH activity were calculated by unconditional logistic regression

It has recently been suggested that bisphOsphOnateS may have directantitumor effects in vivo, in addition to their therapeutic antiresorptiveproperties. Bisphosphonates can inhibit proliferation and cause apoptosis inhuman myeloina cells in vitro. In macrophages, bisphosphonate-induced apoptosis was recently found to be a result of inhibition of the mevalonate(MVA) pathway. The aim of this study was to detennine whether bisphosphonates also affect human myeloma cells in vilro by inhibiting the MVApathway. Incadronate and mevastatin (a known inhibitor of the MVA path.way)caused apoptosis in JJN-3 myeloina caNsand inhibited cell proliferation.Geranylgeraniol and farnesol prevented incadronate-induced apoptosis andhad a partial effect on cell cyde arrest. MVA and geranylgeraniol prevented mevastafin-inducad apoptosis and inhibition of proliferation and completely prevented the effect of mevastatin on the cell cycle. These observations demonstrate that incadronate-induced apoptosis in human myeloma cells invitw is the result of inhibitionof the MVA pathway.