Media type: E-Article Title: The effect of copy number variation in the phase II detoxification genes UGT2B17 and UGT2B28 on colorectal cancer risk Contributor: Angstadt, Andrea Y.; Berg, Arthur; Zhu, Junjia; Miller, Paige; Hartman, Terryl J.; Lesko, Samuel M.; Muscat, Joshua E.; Lazarus, Philip; Gallagher, Carla J. imprint: Wiley, 2013 Published in: Cancer Language: English DOI: 10.1002/cncr.28009 ISSN: 0008-543X; 1097-0142 Origination: Footnote: Description: <jats:sec><jats:title>BACKGROUND</jats:title><jats:p>Genetic polymorphisms in combination with the Western‐style diet, physical inactivity, smoking, excessive alcohol consumption, and obesity have been hypothesized to affect colorectal cancer (CRC) risk. Metabolizers of environmental carcinogenic and endogenous compounds affecting CRC risk include the phase II detoxification UDP‐glucuronosyltransferase (UGT) enzymes UGT2B17 and UGT2B28, which are 2 of the most commonly deleted genes in the genome.</jats:p></jats:sec><jats:sec><jats:title>METHODS</jats:title><jats:p>To study the effect of <jats:italic>UGT2B17</jats:italic> and <jats:italic>UGT2B28</jats:italic> copy number variation (CNV) on CRC risk, 665 Caucasian CRC cases and 621 Caucasian controls were genotyped who had completed extensive demographics and lifestyle questionnaires.</jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p>A significant association between the <jats:italic>UGT2B17</jats:italic> deletion genotype (0/0) and decreased CRC risk was found when the entire population was analyzed (<jats:italic>P</jats:italic> = .044). Stratification by sex yielded a decreased risk (<jats:italic>P</jats:italic> = .020) in men with the <jats:italic>UGT2B17</jats:italic> deletion (0/0), but no association was observed in women (<jats:italic>P</jats:italic> = .724). A significant association between <jats:italic>UGT2B17</jats:italic> (0/0) and decreased risk for rectal (<jats:italic>P</jats:italic> = .0065) but not colon cancer was found. No significant association was found between <jats:italic>UGT2B28</jats:italic> CNV and CRC risk.</jats:p></jats:sec><jats:sec><jats:title>CONCLUSIONS</jats:title><jats:p>The <jats:italic>UGT2B17</jats:italic> deletion genotype (0/0) was associated with a decreased CRC risk in a Caucasian population. After sex stratification, the association was observed in men but not in women, which is consistent with previous findings that men have higher <jats:italic>UGT2B17</jats:italic> expression and activity than women. Because <jats:italic>UGT2B17</jats:italic> metabolizes certain nonsteroidal anti‐inflammatory drugs and flavonoids with antioxidative properties, individuals with a gene deletion may have higher levels of these protective dietary components. <jats:bold><jats:italic>Cancer</jats:italic> 2013;119:2477‐2485</jats:bold>. © <jats:italic>2013 American Cancer Society</jats:italic>.</jats:p></jats:sec> Access State: Open Access