Mi-Sun Lee1, Chen-yu Liu2, Li Su1, David C Christiani3. 1. Environmental and Occupational Medicine and Epidemiology Program, Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA. 2. Institute of Environmental Health, College of Public Health, National Taiwan University, Taipei, Taiwan. 3. Environmental and Occupational Medicine and Epidemiology Program, Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. Electronic address: dchris@hsph.harvard.edu.
Abstract
OBJECTIVES: In this exploratory study, we aimed to investigate whether polymorphisms in excision repair cross-complementing group 1 (ERCC1) and excision repair cross-complementing group 2/xeroderma pigmentosum group D (ERCC2/XPD) in the nucleotide excision repair (NER) pathways associated with DNA adducts in human lung tissue. We also analyzed the association stratified by the major histologic subtypes of non-small cell lung cancer (NSCLC): adenocarcinoma (ADC) and squamous cell carcinoma (SQCC). METHODS: The study population consisted of 107 early stage NSCLC patients from the Massachusetts General Hospital (MGH) in Boston who underwent curative surgical resection. Genotyping was completed for SNPs in ERCC1 [C8092A (rs3212986) and C118T (rs11615)] and ERCC2/XPD [Asp312Asn (rs1799793) and Lys751Gln (rs1052559)] using a PCR-RFLP method and the PCR with fluorescent allele-specific oligonucleotide probes (Taqman). DNA adduct levels were measured as relative adduct levels per 10(10) nucleotides by (32)P-postlabeling in non-tumor lung tissue. RESULTS: After adjusting for potential confounders, lung DNA adduct levels increased by 103.2% [95% confidence interval (CI), -11.5 to 366.6] for ERCC2/XPD rs1799793AA genotype compared with their corresponding wild type homozygous genotypes in overall NSCLC, but the difference did not reach statistical significance. When we stratified by the subtypes of NSCLC, we found that DNA adducts levels in lung increased by 204.9% (95% CI, 0.8 to 822.2, P=0.059) for ERCC2/XPD rs1799793AA genotype in subjects with SQCC and the trend was statistically significant (P for trend=0.0489). CONCLUSIONS: Polymorphisms in ERCC2/XPD Asp312Asn may be associated with increased DNA adduct levels in the lung, especially among subjects with SQCC. Further large scale studies are needed to confirm our findings.
OBJECTIVES: In this exploratory study, we aimed to investigate whether polymorphisms in excision repair cross-complementing group 1 (ERCC1) and excision repair cross-complementing group 2/xeroderma pigmentosum group D (ERCC2/XPD) in the nucleotide excision repair (NER) pathways associated with DNA adducts in human lung tissue. We also analyzed the association stratified by the major histologic subtypes of non-small cell lung cancer (NSCLC): adenocarcinoma (ADC) and squamous cell carcinoma (SQCC). METHODS: The study population consisted of 107 early stage NSCLCpatients from the Massachusetts General Hospital (MGH) in Boston who underwent curative surgical resection. Genotyping was completed for SNPs in ERCC1 [C8092A (rs3212986) and C118T (rs11615)] and ERCC2/XPD [Asp312Asn (rs1799793) and Lys751Gln (rs1052559)] using a PCR-RFLP method and the PCR with fluorescent allele-specific oligonucleotide probes (Taqman). DNA adduct levels were measured as relative adduct levels per 10(10) nucleotides by (32)P-postlabeling in non-tumor lung tissue. RESULTS: After adjusting for potential confounders, lung DNA adduct levels increased by 103.2% [95% confidence interval (CI), -11.5 to 366.6] for ERCC2/XPDrs1799793AA genotype compared with their corresponding wild type homozygous genotypes in overall NSCLC, but the difference did not reach statistical significance. When we stratified by the subtypes of NSCLC, we found that DNA adducts levels in lung increased by 204.9% (95% CI, 0.8 to 822.2, P=0.059) for ERCC2/XPDrs1799793AA genotype in subjects with SQCC and the trend was statistically significant (P for trend=0.0489). CONCLUSIONS: Polymorphisms in ERCC2/XPDAsp312Asn may be associated with increased DNA adduct levels in the lung, especially among subjects with SQCC. Further large scale studies are needed to confirm our findings.
Authors: J K Wiencke; S W Thurston; K T Kelsey; A Varkonyi; J C Wain; E J Mark; D C Christiani Journal: J Natl Cancer Inst Date: 1999-04-07 Impact factor: 13.506
Authors: Thomas C Krivak; Kathleen M Darcy; Chunqiao Tian; Michael Bookman; Holly Gallion; Christine B Ambrosone; Julie A Deloia Journal: Gynecol Oncol Date: 2011-04-14 Impact factor: 5.482
Authors: Wei Zhou; Geoffrey Liu; Sohee Park; Zhaoxi Wang; John C Wain; Thomas J Lynch; Li Su; David C Christiani Journal: Cancer Epidemiol Biomarkers Prev Date: 2005-02 Impact factor: 4.254
Authors: L A Mooney; R M Santella; L Covey; A M Jeffrey; W Bigbee; M C Randall; T B Cooper; R Ottman; W Y Tsai; L Wazneh Journal: Cancer Epidemiol Biomarkers Prev Date: 1995-09 Impact factor: 4.254