Genetic polymorphisms involved in carcinogen metabolism and DNA repair and lung cancer risk in a Japanese population

Chikako Kiyohara, Takahiko Horiuchi, Koichi Takayama, Yoichi Nakanishi

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

BACKGROUND: Several components of overall lung carcinogenesis, carcinogen metabolic and DNA repair pathways may be involved in individual genetic susceptibility to lung cancer. METHODS: We evaluated the role of cytochrome P450 (CYP) 1A1 rs4646903 and rs104894, glutathione S-transferase (GST) M1 and GSTT1 deletion polymorphisms, GSTP1 rs1695, x-ray repair, excision repair cross-complementing group 2 (ERCC2) rs13181, complementing defective in Chinese hamster 1 rs25487, and XRCC3 rs861539 in a case-control study comprising 462 lung cancer cases and 379 controls in a Japanese population. Unconditional logistic regression was used to assess the adjusted odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: CYP1A1 rs4646903 (OR = 1.72, 95% CI = 1.25-2.38), rs1048943 (OR = 1.40, 95% CI = 1.02-1.92), the GSTM1 deletion polymorphism (OR = 1.38, 95% CI = 1.01-1.89), GSTP1 rs1695 (OR =1.48, 95% CI = 1.04-2.11), ERCC2 rs13181 (OR = 1.89, 95% CI = 1.28-2.78), and Chinese hamster 1 rs25487 (OR = 1.54, 95% CI = 1.12-2.13) were associated with lung cancer risk whereas the GSTT1 deletion polymorphism and XRCC3 rs861539 were not. A pertinent combination of multiple "at-risk" genotypes of CYP1A1 rs4646903, the GSTM1 deletion polymorphism and ERCC2 rs13181 was at a 5.94-fold (95% CI = 2.77-12.7) increased risk of lung cancer. CONCLUSIONS: A pertinent combination of multiple at-risk genotypes may detect a high-risk group. Further studies are warranted to verify our findings.

Original languageEnglish
Pages (from-to)954-962
Number of pages9
JournalJournal of Thoracic Oncology
Volume7
Issue number6
DOIs
Publication statusPublished - Jun 2012

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Genetic Polymorphisms
DNA Repair
Carcinogens
Lung Neoplasms
Confidence Intervals
Odds Ratio
Population
Cytochrome P-450 CYP1A1
Cricetulus
Genotype
Genetic Predisposition to Disease
Cytochrome P-450 Enzyme System
Case-Control Studies
Carcinogenesis
Logistic Models
X-Rays
Lung

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Genetic polymorphisms involved in carcinogen metabolism and DNA repair and lung cancer risk in a Japanese population. / Kiyohara, Chikako; Horiuchi, Takahiko; Takayama, Koichi; Nakanishi, Yoichi.

In: Journal of Thoracic Oncology, Vol. 7, No. 6, 06.2012, p. 954-962.

Research output: Contribution to journalArticle

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abstract = "BACKGROUND: Several components of overall lung carcinogenesis, carcinogen metabolic and DNA repair pathways may be involved in individual genetic susceptibility to lung cancer. METHODS: We evaluated the role of cytochrome P450 (CYP) 1A1 rs4646903 and rs104894, glutathione S-transferase (GST) M1 and GSTT1 deletion polymorphisms, GSTP1 rs1695, x-ray repair, excision repair cross-complementing group 2 (ERCC2) rs13181, complementing defective in Chinese hamster 1 rs25487, and XRCC3 rs861539 in a case-control study comprising 462 lung cancer cases and 379 controls in a Japanese population. Unconditional logistic regression was used to assess the adjusted odds ratios (OR) and 95{\%} confidence intervals (95{\%} CI). RESULTS: CYP1A1 rs4646903 (OR = 1.72, 95{\%} CI = 1.25-2.38), rs1048943 (OR = 1.40, 95{\%} CI = 1.02-1.92), the GSTM1 deletion polymorphism (OR = 1.38, 95{\%} CI = 1.01-1.89), GSTP1 rs1695 (OR =1.48, 95{\%} CI = 1.04-2.11), ERCC2 rs13181 (OR = 1.89, 95{\%} CI = 1.28-2.78), and Chinese hamster 1 rs25487 (OR = 1.54, 95{\%} CI = 1.12-2.13) were associated with lung cancer risk whereas the GSTT1 deletion polymorphism and XRCC3 rs861539 were not. A pertinent combination of multiple {"}at-risk{"} genotypes of CYP1A1 rs4646903, the GSTM1 deletion polymorphism and ERCC2 rs13181 was at a 5.94-fold (95{\%} CI = 2.77-12.7) increased risk of lung cancer. CONCLUSIONS: A pertinent combination of multiple at-risk genotypes may detect a high-risk group. Further studies are warranted to verify our findings.",
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N2 - BACKGROUND: Several components of overall lung carcinogenesis, carcinogen metabolic and DNA repair pathways may be involved in individual genetic susceptibility to lung cancer. METHODS: We evaluated the role of cytochrome P450 (CYP) 1A1 rs4646903 and rs104894, glutathione S-transferase (GST) M1 and GSTT1 deletion polymorphisms, GSTP1 rs1695, x-ray repair, excision repair cross-complementing group 2 (ERCC2) rs13181, complementing defective in Chinese hamster 1 rs25487, and XRCC3 rs861539 in a case-control study comprising 462 lung cancer cases and 379 controls in a Japanese population. Unconditional logistic regression was used to assess the adjusted odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: CYP1A1 rs4646903 (OR = 1.72, 95% CI = 1.25-2.38), rs1048943 (OR = 1.40, 95% CI = 1.02-1.92), the GSTM1 deletion polymorphism (OR = 1.38, 95% CI = 1.01-1.89), GSTP1 rs1695 (OR =1.48, 95% CI = 1.04-2.11), ERCC2 rs13181 (OR = 1.89, 95% CI = 1.28-2.78), and Chinese hamster 1 rs25487 (OR = 1.54, 95% CI = 1.12-2.13) were associated with lung cancer risk whereas the GSTT1 deletion polymorphism and XRCC3 rs861539 were not. A pertinent combination of multiple "at-risk" genotypes of CYP1A1 rs4646903, the GSTM1 deletion polymorphism and ERCC2 rs13181 was at a 5.94-fold (95% CI = 2.77-12.7) increased risk of lung cancer. CONCLUSIONS: A pertinent combination of multiple at-risk genotypes may detect a high-risk group. Further studies are warranted to verify our findings.

AB - BACKGROUND: Several components of overall lung carcinogenesis, carcinogen metabolic and DNA repair pathways may be involved in individual genetic susceptibility to lung cancer. METHODS: We evaluated the role of cytochrome P450 (CYP) 1A1 rs4646903 and rs104894, glutathione S-transferase (GST) M1 and GSTT1 deletion polymorphisms, GSTP1 rs1695, x-ray repair, excision repair cross-complementing group 2 (ERCC2) rs13181, complementing defective in Chinese hamster 1 rs25487, and XRCC3 rs861539 in a case-control study comprising 462 lung cancer cases and 379 controls in a Japanese population. Unconditional logistic regression was used to assess the adjusted odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: CYP1A1 rs4646903 (OR = 1.72, 95% CI = 1.25-2.38), rs1048943 (OR = 1.40, 95% CI = 1.02-1.92), the GSTM1 deletion polymorphism (OR = 1.38, 95% CI = 1.01-1.89), GSTP1 rs1695 (OR =1.48, 95% CI = 1.04-2.11), ERCC2 rs13181 (OR = 1.89, 95% CI = 1.28-2.78), and Chinese hamster 1 rs25487 (OR = 1.54, 95% CI = 1.12-2.13) were associated with lung cancer risk whereas the GSTT1 deletion polymorphism and XRCC3 rs861539 were not. A pertinent combination of multiple "at-risk" genotypes of CYP1A1 rs4646903, the GSTM1 deletion polymorphism and ERCC2 rs13181 was at a 5.94-fold (95% CI = 2.77-12.7) increased risk of lung cancer. CONCLUSIONS: A pertinent combination of multiple at-risk genotypes may detect a high-risk group. Further studies are warranted to verify our findings.

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