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

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

doi:10.1002/cncr.28009

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

Journal article

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Peer reviewed

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

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

Cancer, Vol.119(13), pp.2477-2485

07/01/2013

DOI: https://doi.org/10.1002/cncr.28009

Handle:

https://hdl.handle.net/2376/108986

PMCID: PMC3686841

PMID: 23575887

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https://doi.org/10.1002/cncr.28009View

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Abstract

Colonic Neoplasms - genetics

Minor Histocompatibility Antigens

Colorectal Neoplasms - genetics

Humans

Middle Aged

Male

Case-Control Studies

DNA Copy Number Variations

Glucuronosyltransferase - genetics

Rectal Neoplasms - genetics

Gene Deletion

Metabolic Detoxication, Phase II - genetics

Adult

Female

Surveys and Questionnaires

Pennsylvania - epidemiology

Colorectal Neoplasms - epidemiology

Colorectal Neoplasms - enzymology

European Continental Ancestry Group - genetics

Genetic Predisposition to Disease

Risk Factors

Genotype

Meat - adverse effects

Sex Factors

Aged

Meat Products - adverse effects

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. 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. 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. 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.

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Title: The effect of copy number variation in the phase II detoxification genes UGT2B17 and UGT2B28 on colorectal cancer risk
Creators: Andrea Y Angstadt - Department of Public Health Sciences, Penn State College of Medicine, Hershey, Pennsylvania 17033, USA
Arthur Berg
Junjia Zhu
Paige Miller
Terryl J Hartman
Samuel M Lesko
Joshua E Muscat
Philip Lazarus
Carla J Gallagher
Publication Details: Cancer, Vol.119(13), pp.2477-2485
Academic Unit: Pharmaceutical Sciences, Department of
Publisher: United States
Grant note: R00 CA 131477 / NCI NIH HHS R00 CA131477 / NCI NIH HHS R24 HD041025 / NICHD NIH HHS
Identifiers: 99900547106001842
Language: English
Resource Type: Journal article