The effect of copy number variation in the phase II detoxification genes UGT2B17 and UGT2B28 on colorectal cancer risk. Article

Angstadt, Andrea Y, Berg, Arthur, Zhu, Junjia et al. (2013). The effect of copy number variation in the phase II detoxification genes UGT2B17 and UGT2B28 on colorectal cancer risk. . 119(13), 2477-2485. 10.1002/cncr.28009

cited authors

  • Angstadt, Andrea Y; Berg, Arthur; Zhu, Junjia; Miller, Paige; Hartman, Terryl J; Lesko, Samuel M; Muscat, Joshua E; Lazarus, Philip; Gallagher, Carla J

fiu authors

abstract

  • Background

    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.

    Methods

    To study the effect of UGT2B17 and UGT2B28 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.

    Results

    A significant association between the UGT2B17 deletion genotype (0/0) and decreased CRC risk was found when the entire population was analyzed (P = .044). Stratification by sex yielded a decreased risk (P = .020) in men with the UGT2B17 deletion (0/0), but no association was observed in women (P = .724). A significant association between UGT2B17 (0/0) and decreased risk for rectal (P = .0065) but not colon cancer was found. No significant association was found between UGT2B28 CNV and CRC risk.

    Conclusions

    The UGT2B17 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 UGT2B17 expression and activity than women. Because UGT2B17 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.

publication date

  • July 1, 2013

keywords

  • Adult
  • Aged
  • Case-Control Studies
  • Colonic Neoplasms
  • Colorectal Neoplasms
  • DNA Copy Number Variations
  • European Continental Ancestry Group
  • Female
  • Gene Deletion
  • Genetic Predisposition to Disease
  • Genotype
  • Glucuronosyltransferase
  • Humans
  • Male
  • Meat
  • Meat Products
  • Metabolic Detoxication, Phase II
  • Middle Aged
  • Minor Histocompatibility Antigens
  • Pennsylvania
  • Rectal Neoplasms
  • Risk Factors
  • Sex Factors
  • Surveys and Questionnaires

Digital Object Identifier (DOI)

Medium

  • Print-Electronic

start page

  • 2477

end page

  • 2485

volume

  • 119

issue

  • 13