Sukhendu Das

© 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.

In the light of corporate governance standards envisaged by the recent amendments to the Companies Act, 1956, and the provisions of Sebi's revised Clause 49 of the Listing Agreement, this case study evaluates the quality of corporate governance standards and present practices in the textile, synthetics and petrochemical industry in India, based on the annual report of Reliance Industries Limited (RIL), a major Indian corporate house for the financial year 2006-2007. The study is expected to serve as a pointer to the effectiveness of current corporate governance practice in RIL, in particular, and the Indian corporate sector, in general.