Thymidylate synthase polymorphisms in genomic DNA as clinical outcome predictors in a European population of advanced non-small cell lung cancer patients receiving pemetrexed

BACKGROUND: We studied whether thymidylate synthase (TS) genotype has an independent prognostic/predictive impact on a European population of advanced non-small cell lung cancer (NSCLC) patients receiving pemetrexed. METHODS: Twenty-five patients treated with pemetrexed-based regimens were included. Genomic DNA was isolated prior to treatment. The variable number of tandem repeat (VNTR) polymorphisms, the G > C single nucleotide polymorphisms (SNP) and the TS 6-bp insertion/deletion (6/6) in the 3' untranslated region (UTR) polymorphisms were analyzed and correlated with overall response rate (ORR), progression-free survival (PFS), overall-survival (OS) and toxicity. RESULTS: The genotype +6/+6 predicted a higher ORR among active/former smokers compared to +6/-6 genotype (100% vs. 50%; p = 0.085). Overall, the 3R/3R genotype predicted a higher ORR (100%) over the rest VNTR polymorphisms (p = 0.055). The presence of 3R/3R genotype significantly correlated with a superior ORR in patients without EGFR activating mutations (100%) compared to 2R/2R, 2R/3R and 3R/4R genotype (77.8%, 33.3% and 0% respectively; p = 0.017). After a median follow-up of 21 months, a trend towards a better PFS, although not significant, was found among subjects showing 3R/3R polymorphisms (p = 0.089). A significantly superior OS was found in patients showing 3R/3R genotype rather than other VNTR polymorphisms (p = 0.019). No significant correlation with the toxicity was observed. CONCLUSION: In our series, 3R/3R polymorphism correlated with a superior OS. Also, this polymorphism, when associated to wild type EGFR, was related to a higher ORR to pemetrexed. Toxicity was not significantly correlated with a specific TS genotype

Basques in Cuba

Taking as their inspiration and cue Jon Bilbao's book Vascos en Cuba 1492-1511, the authors of this book, a collection of international academics, take up the subject of the involvement of the Basque people in Cuba from a variety of viewpoints and analytical and theoretical perspectives. The Basque Country has had a long and varied relationship with Cuba, its people, and its history. The chapters in this volume trace that connection based on diverse topics and viewpoints: the representations of Basques in classic Cuban poetry and Cuba as a topic in the nineteenth-century Basque novel; the involvement of the Basques in the African slave trade, the role of the Tree of Gernika in Cuba's Templete monument, the service of Basque parliamentarians and soldiers in Spain's former colony, and the politics of Basque priests on the island are all treated, as well as much more. There are also chapters that consider the involvement of Basques regionally, in places such as Cienfuegos, Santiago de Cuba, Vueltabajo, and Havana. Edited by renowned Basque scholar William A. Douglass, the volume provides an important contribution in reclaiming a mostly neglected history.This book was published with generous financial support from the Basque Government