PMID- 15551330
OWN - NLM
STAT- MEDLINE
DCOM- 20050323
LR  - 20160303
IS  - 0020-7136 (Print)
IS  - 0020-7136 (Linking)
VI  - 114
IP  - 3
DP  - 2005 Apr 10
TI  - hOGG1 Ser326Cys polymorphism and G:C-to-T:A mutations: no evidence for a role in 
      tobacco-related non small cell lung cancer.
PG  - 387-93
AB  - Human 8-oxoguanine DNA glycosylase 1 (hOGG1) plays a major role in the repair of 
      8-hydroxyguanine, one of the major forms of DNA damage generated by reactive 
      oxygen species in tobacco smoke. If left unrepaired by hOGG1, 8-hydroxyguanine 
      can produce G:C-to-T:A transversions. Recent studies have suggested that the 
      hOGG1 Ser326Cys polymorphism is associated with both a decrease in enzyme 
      activity and an increased risk of lung cancer. To define the interaction between 
      tobacco carcinogens, hOGG1-mediated DNA repair and DNA damage, we examined the 
      role of the hOGG1 Ser326Cys polymorphism in mutation of the p53 gene in non small 
      cell lung cancer (NSCLC). Tumor and nonneoplastic DNA were collected from 141 
      cigarette smokers with NSCLC. p53 mutations were detected by direct dideoxy 
      sequencing and/or the GeneChip p53 assay in 74 of the 141 (52%) tumors. hOGG1 
      codon 326 polymorphisms were identified by polymerase chain reaction-restriction 
      fragment length polymorphism analysis. The distribution of hOGG1 codon 326 
      genotypes was Ser/Ser, 90 of 141 (64%); Ser/Cys, 45 of 141 (32%); and Cys/Cys, 6 
      of 141 (4%). p53 mutations were significantly (p = 0.04) less common in NSCLC 
      from patients with codon 326 Ser/Cys or Cys/Cys genotypes (21 of 51; 41%) than in 
      NSCLC from Ser/Ser homozygotes (53 of 90; 59%). The decrease in p53 mutation 
      frequency among carriers of the Cys allele was more evident in lung squamous cell 
      cancer [7 of 17 (41%) for Cys/Cys and Ser/Cys vs. 27 of 38 (71%) for Ser/Ser; p = 
      0.04] than in nonbronchoalveolar adenocarcinoma [11 of 26 (42%) for Cys/Cys and 
      Ser/Cys vs. 20 of 35 (57%) for Ser/Ser; p = 0.25]. The prevalence of G:C-to-T:A 
      transversions was similar among hOGG1 codon 326 genotypes. In summary, the hOGG1 
      codon 326 Cys allele was associated with a decrease in p53 mutations and no 
      effect on G:C-to-T:A transversions in NSCLC. This decrease in p53 mutations in 
      vivo is not consistent with a decrease in the repair of 8-hydroxyguanine among 
      carriers of the hOGG1 codon 326 Cys allele in vitro.
CI  - (c) 2004 Wiley-Liss, Inc.
FAU - Hu, Ying Chuan
AU  - Hu YC
AD  - Department of Surgery, University of Rochester Medical School, Rochester, NY 
      14642, USA.
FAU - Ahrendt, Steven A
AU  - Ahrendt SA
LA  - eng
GR  - K08 CA76452-01/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (Codon)
RN  - EC 3.2.2.- (DNA Glycosylases)
RN  - EC 3.2.2.- (oxoguanine glycosylase 1, human)
SB  - IM
MH  - Aged
MH  - Carcinoma, Non-Small-Cell Lung/*genetics/*physiopathology
MH  - Codon
MH  - DNA Damage
MH  - DNA Glycosylases/*genetics/pharmacology
MH  - DNA Repair
MH  - Female
MH  - Genes, p53/*genetics
MH  - Genetic Predisposition to Disease
MH  - Genotype
MH  - Humans
MH  - Lung Neoplasms/*genetics/*physiopathology
MH  - Male
MH  - Middle Aged
MH  - Oligonucleotide Array Sequence Analysis
MH  - Point Mutation
MH  - *Polymorphism, Genetic
MH  - Smoking/*adverse effects
EDAT- 2004/11/20 09:00
MHDA- 2005/03/24 09:00
CRDT- 2004/11/20 09:00
PHST- 2004/11/20 09:00 [pubmed]
PHST- 2005/03/24 09:00 [medline]
PHST- 2004/11/20 09:00 [entrez]
AID - 10.1002/ijc.20730 [doi]
PST - ppublish
SO  - Int J Cancer. 2005 Apr 10;114(3):387-93. doi: 10.1002/ijc.20730.