Paul Chen

© 2014 American Association for Cancer Research.Background: Identifying sources of variation in the nicotine and nitrosamine metabolic inactivation pathways is important to understanding the relationship between smoking and cancer risk. Numerous UGT1A and UGT2B enzymes are implicated in nicotine and nitrosamine metabolism in vitro; however, little is known about their roles in vivo. Methods: Within UGT1A1, UGT1A4, UGT1A9, UGT2B7, UGT2B10, and UGT2B17, 47 variants were genotyped, including UGT2B10∗2 and UGT2B17∗2. The association between variation in these UGTs and glucuronidation activity within European and African American current smokers, quantified as urinary ratios of the glucuronide over unconjugated compound for nicotine, cotinine, trans-30-hydroxycotinine, and 4--1--1-butanol, was investigated in regression models assuming a dominant effect of variant alleles. Results: Correcting for multiple testing, three UGT2B10 variants were associated with cotinine glucuronidation, rs2331559 and rs11726322 in European Americans and rs835309 in African Americans. Additional variants predominantly in UGT2B10 were nominally associated with nicotine and cotinine glucuronidation in both ethnicities in addition to UGT2B10∗2 in European Americans. UGT2B17∗2 in European Americans and UGT2B7 variants in African Americans were nominally associated with 3HC glucuronidation. UGT1A, UGT2B10, and UGT2B7 variants in African Americans were nominally associated with NNAL glucuronidation. Conclusions: Findings from this initial in vivo study support a role for multiple UGTs in the glucuronidation of tobacco-related compounds in vivo, in particular UGT2B10 and cotinine glucuronidation. Impact: Findings also provide insight into ethnic differences in glucuronidation activity, which could be contributing to ethnic disparities in the risk for smoking-related cancers.

© The Author 2016.Charge density wave formation, a key physics issue for materials, arises from interactions among electrons and phonons that can also lead to superconductivity and other competing or entangled phases. The prototypical system TiSe 2, with a particularly simple transition and no Kohn anomalies caused by electron-phonon coupling, is a fascinating but unsolved case after decades of research. Our angle-resolved photoemission measurements of the band structure as a function of temperature, aided by first-principles calculations, reveal a hitherto undetected but crucial feature: a electronic order in each layer sets in at ∼232 K before the widely recognized three-dimensional structural order at ∼205 K. The dimensional crossover, likely a generic feature of such layered materials, involves renormalization of different band gaps in two stages.