Genetic polymorphisms of GSTP1 and XRCC1: prediction of clinical outcome of platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC) patients.
BACKGROUND
Platinum agents cause DNA cross-linking and oxidative damage. Genetic polymorphisms of GSTP1 and XRCC1 involved in glutathione metabolic and DNA repair pathways may explain inter individual differences in chemosensitivity and clinical outcome in NSCLC patients treated with platinum-based regimens.


METHODS
We used DNA sequencing methods to evaluate genetic polymorphisms of the GSTP1A313G and XRCC1G28152A in 111 patients with stage IV NSCLC treated with platinum-based chemotherapy. Clinical response was evaluated according to RECIST criteria after 2-3 cycles of chemotherapy and time to progression (TTP) was calculated from the time of initial treatment to disease progression.


RESULTS
GSTP1A313G and XRCC1G28152A polymorphisms, both alone and in combination, were significantly associated with response to treatment and clinical outcome (p <0.05) in NSCLC patients treated with platinum-based chemotherapy. These polymorphisms independently predicted clinical outcome even after taking into account age, gender, tumour histology, tumour differentiation and chemotherapy regimens.


CONCLUSIONS
Genetic polymorphisms of GSTP1 and XRCC1 may be important predictive factors in platinum-treated patients with advanced NSCLC. Assessment of genetic variations of GSTP1 and XRCC1 could facilitate therapeutic decisions for individualised therapy in advanced NSCLC.
Department of Oncology, The Affiliated Hospital of Medical College, Qing Dao University, Qingdao, Shandong Province, China.
Fei
F
Zhou
Zhuang
Z
Yu
Tao
T
Jiang
Hongying
H
Lv
Ruyong
R
Yao
Jun
J
Liang
D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D010984:Platinum / Q000008:administration & dosage / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D000076105:X-ray Repair Cross Complementing Protein 1
D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D010984:Platinum; D051549:Glutathione S-Transferase pi