Polymorphisms in p53, GSTP1 and XRCC1 predict relapse and survival of gastric cancer patients treated with oxaliplatin-based adjuvant chemotherapy.
OBJECTIVE
The aim of this study was to assess whether genetic polymorphisms in p53, glutathione S-transferase P1 (GSTP1), GSTM1, excision repair cross complementing group 1 (ERCC1) and X-ray repair cross-complementing group 1 (XRCC1) genes are associated with clinical outcome of gastric cancer patients treated with oxaliplatin-based adjuvant chemotherapy.


METHODS
The genetic polymorphisms in p53, GSTP1, GSTM1 (null), ERCC1 and XRCC1 were determined in 102 gastric cancer patients treated with oxaliplatin-based adjuvant chemotherapy using polymerase chain reaction-ligation detection reaction method.


RESULTS
Among the five studied polymorphisms, p53 codon 72 Pro/Pro, GSTP1 codon 105 Ile/Ile, and XRCC1 codon 399 Gln/Gln + Arg/Gln were associated with poor relapse-free survival and overall survival (P < 0.05); and the prognostic effect was retained in the Cox multivariate analysis. Combination analysis with the three polymorphisms using the Kaplan-Meier method and Cox multivariate analysis revealed that the relapse-free and overall survivals significantly increase with the number of favorable genotypes (P < 0.05). No significant association was found between the GSTM1 (null) or the ERCC1 codon 118 genotypes and the clinical outcome (P > 0.05).


CONCLUSIONS
Testing for p53 Arg72Pro, GSTP1 Ile105Val, and XRCC1 Arg399Gln polymorphisms may allow identification of gastric cancer patients who will benefit from oxaliplatin-based adjuvant chemotherapy. Selecting specific adjuvant treatments according to the individual genetic background may represent an innovative strategy that warrants prospective studies.
Huang
Zhao-Hui
ZH
Department of Pathology, Cancer Hospital, Fudan University, Shanghai, China. hzhwxsy@yahoo.com.cn
Hua
Dong
D
Du
Xiang
X
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D003062:Codon / Q000235:genetics; D004260:DNA Repair / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D000077150:Oxaliplatin; D011110:Polymorphism, Genetic; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D016019:Survival Analysis; D016896:Treatment Outcome; D000076105:X-ray Repair Cross Complementing Protein 1
D000970:Antineoplastic Agents; D003062:Codon; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D009944:Organoplatinum Compounds; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D000077150:Oxaliplatin; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi