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Background  The human 8‐oxoguanine DNA glycosylase 1 ( hOGG1 ) gene encodes a DNA glycosylase that removes 8‐hydroxy‐2‐deoxyguanine (8‐OH‐dG) DNA damage to protect against gene mutations. The association of  hOGG1  Ser326Cys polymorphism with lung cancer risk has predicted that  hOGG1 ‐Cys variants are less effective at removing 8‐OH‐dG damage from DNA; therefore, these variants might show an increased occurrence of tumor suppressor gene and oncogene mutations. However, no evidence has yet supported this hypothesis.    Methods  Direct sequencing was performed to examine the mutations of  p53  and EGFR genes in lung tumors from patients with non‐small cell lung cancer (NSCLC). Polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) was used to examine  hOGG1  Ser326Cys polymorphism in this study population.    Results  A total of 99  p53 ‐mutated and 99  EGFR ‐mutated patients with NSCLC were selected to explore the possible associations of these mutations with  hOGG1  Ser326Cys polymorphism. The  p53 ‐mutated and  EGFR ‐mutated patients were divided into nondeletion and deletion subgroups.  P53  deletion mutations were more commonly observed in male than in female patients ( P  = 0.030). However,  EGFR  exon 19 deletion mutations were more prevalent in female and adenocarcinoma patients than in male and squamous cell carcinoma patients ( P  = 0.028 for genders,  P  = 0.017 for tumor histology). Interestingly,  p53  and  EGFR  exon 19 deletion mutations were more frequent in patients with  hOGG1  Ser/Cys + Cys/Cys  hOGG1 ‐Cys variants than with the  hOGG1  Ser/Ser genotype ( P  = 0.010 for  p53 ,  P  = 0.032 for  EGFR ).    Conclusions  We suggest that the association of  hOGG1  Ser326Cys polymorphism with lung cancer risk could be partially explained by increases in  p53  and  EGFR  deletion mutations.    Key points    Significant findings of the study    NSCLC patients with  hOGG1 ‐Cys variants may have a higher risk of  p53  and  EGFR  deletion mutations than with  hOGG1  Ser/Ser genotype.What this study adds    NSCLC patients with  hOGG1 ‐Cys variants might be helpful to predict patients having higher risk of  EGFR  exon 19 deletion mutations and these patients who were treated with gefitinib or erlotinib could be a higher risk to occur  EGFR  T790M mutation.

Association of hOGG1 ‐Cys variants with occurrence of p53 and EGFR deletion mutations in non‐small cell lung cancer