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 Johnson Hartman, Samuel M. Lesko, Joshua Muscat, Philip Lazarus, Carla J. Gallagher

Research output: Contribution to journalArticle

30 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2477-2485
Number of pages9
JournalCancer
Volume119
Issue number13
DOIs
StatePublished - Jul 1 2013

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Phase II Metabolic Detoxication
Colorectal Neoplasms
Genes
Genotype
Glucuronosyltransferase
UGT2B28 UDP-glucuronosyltransferase
Gene Deletion
Genetic Polymorphisms
Flavonoids
Alcohol Drinking
Colonic Neoplasms
Population
Life Style
Anti-Inflammatory Agents
Obesity
Smoking
Demography
Genome
Diet

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Oncology

Cite this

Angstadt, Andrea Y. ; Berg, Arthur ; Zhu, Junjia ; Miller, Paige ; Hartman, Terryl Johnson ; Lesko, Samuel M. ; Muscat, Joshua ; Lazarus, Philip ; Gallagher, Carla J. / The effect of copy number variation in the phase II detoxification genes UGT2B17 and UGT2B28 on colorectal cancer risk. In: Cancer. 2013 ; Vol. 119, No. 13. pp. 2477-2485.
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title = "The effect of copy number variation in the phase II detoxification genes UGT2B17 and UGT2B28 on colorectal cancer risk",
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.",
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The effect of copy number variation in the phase II detoxification genes UGT2B17 and UGT2B28 on colorectal cancer risk. / Angstadt, Andrea Y.; Berg, Arthur; Zhu, Junjia; Miller, Paige; Hartman, Terryl Johnson; Lesko, Samuel M.; Muscat, Joshua; Lazarus, Philip; Gallagher, Carla J.

In: Cancer, Vol. 119, No. 13, 01.07.2013, p. 2477-2485.

Research output: Contribution to journalArticle

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T1 - The effect of copy number variation in the phase II detoxification genes UGT2B17 and UGT2B28 on colorectal cancer risk

AU - Angstadt, Andrea Y.

AU - Berg, Arthur

AU - Zhu, Junjia

AU - Miller, Paige

AU - Hartman, Terryl Johnson

AU - Lesko, Samuel M.

AU - Muscat, Joshua

AU - Lazarus, Philip

AU - Gallagher, Carla J.

PY - 2013/7/1

Y1 - 2013/7/1

N2 - 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.

AB - 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.

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