Polymorphisms of xenobiotic-metabolizing genes and colorectal cancer risk in patients with lynch syndrome: A retrospective cohort study in Taiwan

Abram Bunya Kamiza, Jeng Fu You, Wen Chang Wang, Reiping Tang, Chun Yu Chang, Huei Tzu Chien, Chih Hsiung Lai, Li Ling Chiu, Tsai Ping Lo, Kuan Yi Hung, Chao A. Hsiung, Chih Ching Yeh

Research output: Contribution to journalArticle

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Abstract

Cytochrome P450 (CYP), glutathione-S-transferase (GST), and N-acetyltransferase (NAT) are crucial for metabolism and clearance of xenobiotics. This study investigated whether CYP, GST, and NAT single nucleotide polymorphisms (SNPs) are associated with colorectal cancer (CRC) in patients with Lynch syndrome. The interaction between these SNPs and cigarette smoking or meat consumption was also explored. We identified 270 patients with Lynch syndrome from the Taiwan Hereditary Nonpolyposis Colorectal Cancer Consortium. A weighted Cox proportional hazard model was used to calculate the hazard ratios (HRs) and 95% confidence interval (CIs). The GSTA1 rs3957356 TT (HR=5.36, 95% CI=2.39-12.0) and CYP1B1 rs1056836 CC (HR=7.24, 95% CI=3.51-14.9) were significantly associated with CRC risk when compared to wild-type CC and GG genotypes, respectively. However, the CYP1A1 rs4646903 CC genotype significantly reduced the risk of CRC (HR=0.33, 95% CI=0.12-0.89) when compared to TT genotype. Moreover, significant interactions were observed between NAT1 acetylation and CYP1B1 rs1056827 and meat consumption.Our results suggest that xenobiotic-metabolizing SNPs are not only associated with CRC risk in patients with Lynch syndrome in Taiwan but also interact with meat consumption to modify the disease risk.

Original languageEnglish
JournalEnvironmental and Molecular Mutagenesis
DOIs
Publication statusPublished - 2018

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Hereditary Nonpolyposis Colorectal Neoplasms
Xenobiotics
Taiwan
Colorectal Neoplasms
Cohort Studies
Retrospective Studies
Confidence Intervals
Meat
Single Nucleotide Polymorphism
Acetyltransferases
Genotype
Glutathione Transferase
Cytochrome P-450 Enzyme System
Genes
Cytochrome P-450 CYP1A1
Acetylation
Proportional Hazards Models
Smoking

Keywords

  • Colorectal cancer
  • Cytochrome P450
  • Glutathione-S-transferase
  • Lynch syndrome
  • N-acetyltransferase
  • Taiwan

ASJC Scopus subject areas

  • Epidemiology
  • Genetics(clinical)
  • Health, Toxicology and Mutagenesis

Cite this

Polymorphisms of xenobiotic-metabolizing genes and colorectal cancer risk in patients with lynch syndrome : A retrospective cohort study in Taiwan. / Kamiza, Abram Bunya; You, Jeng Fu; Wang, Wen Chang; Tang, Reiping; Chang, Chun Yu; Chien, Huei Tzu; Lai, Chih Hsiung; Chiu, Li Ling; Lo, Tsai Ping; Hung, Kuan Yi; Hsiung, Chao A.; Yeh, Chih Ching.

In: Environmental and Molecular Mutagenesis, 2018.

Research output: Contribution to journalArticle

Kamiza, Abram Bunya ; You, Jeng Fu ; Wang, Wen Chang ; Tang, Reiping ; Chang, Chun Yu ; Chien, Huei Tzu ; Lai, Chih Hsiung ; Chiu, Li Ling ; Lo, Tsai Ping ; Hung, Kuan Yi ; Hsiung, Chao A. ; Yeh, Chih Ching. / Polymorphisms of xenobiotic-metabolizing genes and colorectal cancer risk in patients with lynch syndrome : A retrospective cohort study in Taiwan. In: Environmental and Molecular Mutagenesis. 2018.
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abstract = "Cytochrome P450 (CYP), glutathione-S-transferase (GST), and N-acetyltransferase (NAT) are crucial for metabolism and clearance of xenobiotics. This study investigated whether CYP, GST, and NAT single nucleotide polymorphisms (SNPs) are associated with colorectal cancer (CRC) in patients with Lynch syndrome. The interaction between these SNPs and cigarette smoking or meat consumption was also explored. We identified 270 patients with Lynch syndrome from the Taiwan Hereditary Nonpolyposis Colorectal Cancer Consortium. A weighted Cox proportional hazard model was used to calculate the hazard ratios (HRs) and 95{\%} confidence interval (CIs). The GSTA1 rs3957356 TT (HR=5.36, 95{\%} CI=2.39-12.0) and CYP1B1 rs1056836 CC (HR=7.24, 95{\%} CI=3.51-14.9) were significantly associated with CRC risk when compared to wild-type CC and GG genotypes, respectively. However, the CYP1A1 rs4646903 CC genotype significantly reduced the risk of CRC (HR=0.33, 95{\%} CI=0.12-0.89) when compared to TT genotype. Moreover, significant interactions were observed between NAT1 acetylation and CYP1B1 rs1056827 and meat consumption.Our results suggest that xenobiotic-metabolizing SNPs are not only associated with CRC risk in patients with Lynch syndrome in Taiwan but also interact with meat consumption to modify the disease risk.",
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AU - Kamiza, Abram Bunya

AU - You, Jeng Fu

AU - Wang, Wen Chang

AU - Tang, Reiping

AU - Chang, Chun Yu

AU - Chien, Huei Tzu

AU - Lai, Chih Hsiung

AU - Chiu, Li Ling

AU - Lo, Tsai Ping

AU - Hung, Kuan Yi

AU - Hsiung, Chao A.

AU - Yeh, Chih Ching

PY - 2018

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N2 - Cytochrome P450 (CYP), glutathione-S-transferase (GST), and N-acetyltransferase (NAT) are crucial for metabolism and clearance of xenobiotics. This study investigated whether CYP, GST, and NAT single nucleotide polymorphisms (SNPs) are associated with colorectal cancer (CRC) in patients with Lynch syndrome. The interaction between these SNPs and cigarette smoking or meat consumption was also explored. We identified 270 patients with Lynch syndrome from the Taiwan Hereditary Nonpolyposis Colorectal Cancer Consortium. A weighted Cox proportional hazard model was used to calculate the hazard ratios (HRs) and 95% confidence interval (CIs). The GSTA1 rs3957356 TT (HR=5.36, 95% CI=2.39-12.0) and CYP1B1 rs1056836 CC (HR=7.24, 95% CI=3.51-14.9) were significantly associated with CRC risk when compared to wild-type CC and GG genotypes, respectively. However, the CYP1A1 rs4646903 CC genotype significantly reduced the risk of CRC (HR=0.33, 95% CI=0.12-0.89) when compared to TT genotype. Moreover, significant interactions were observed between NAT1 acetylation and CYP1B1 rs1056827 and meat consumption.Our results suggest that xenobiotic-metabolizing SNPs are not only associated with CRC risk in patients with Lynch syndrome in Taiwan but also interact with meat consumption to modify the disease risk.

AB - Cytochrome P450 (CYP), glutathione-S-transferase (GST), and N-acetyltransferase (NAT) are crucial for metabolism and clearance of xenobiotics. This study investigated whether CYP, GST, and NAT single nucleotide polymorphisms (SNPs) are associated with colorectal cancer (CRC) in patients with Lynch syndrome. The interaction between these SNPs and cigarette smoking or meat consumption was also explored. We identified 270 patients with Lynch syndrome from the Taiwan Hereditary Nonpolyposis Colorectal Cancer Consortium. A weighted Cox proportional hazard model was used to calculate the hazard ratios (HRs) and 95% confidence interval (CIs). The GSTA1 rs3957356 TT (HR=5.36, 95% CI=2.39-12.0) and CYP1B1 rs1056836 CC (HR=7.24, 95% CI=3.51-14.9) were significantly associated with CRC risk when compared to wild-type CC and GG genotypes, respectively. However, the CYP1A1 rs4646903 CC genotype significantly reduced the risk of CRC (HR=0.33, 95% CI=0.12-0.89) when compared to TT genotype. Moreover, significant interactions were observed between NAT1 acetylation and CYP1B1 rs1056827 and meat consumption.Our results suggest that xenobiotic-metabolizing SNPs are not only associated with CRC risk in patients with Lynch syndrome in Taiwan but also interact with meat consumption to modify the disease risk.

KW - Colorectal cancer

KW - Cytochrome P450

KW - Glutathione-S-transferase

KW - Lynch syndrome

KW - N-acetyltransferase

KW - Taiwan

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