Lack of influence of XRCC1 and XPD gene polymorphisms on outcome of platinum-based chemotherapy for advanced non small cell lung cancers.
OBJECTIVE
Genetic polymorphisms of DNA repair genes are associated with differential enzyme activity and may help explain interindividual differences in response rates after platinum-based chemotherapy for non small cell lung cancers (NSCLCs). This study was conducted to assess relationships between X-ray repair cross complementing group1 (XRCC1) and xeroderma pigmentosum group D (XPD) genetic polymorphisms and outcome in NSCLC patients.


METHODS
From March 1, 2005 to December 31, 2008, the polymerase chain reaction-restriction fragment length polymorphism method was applied to evaluate genetic polymorphisms of the XRCC1 codon399 (Arg/Gln) and XPD codon751 (Lys/Gln) DNA repair genes in 108 patients with stage IIIB and IV NSCLCs treated with platinum-based chemotherapy in the Department of Chemotherapy of Jiangsu Cancer Hospital and Research Institute.


RESULTS
Among the assessed NSCLC patients, the overall response rate of chemotherapy was 21.6%. No association was found with either of the genetic polymorphisms, although the XRCC1 399Arg/Arg genotype was associated with a non-significant higher median survival time (29 months versus 21 months for the Arg/Gln genotype and 15 months for the Gln/Gln genotype, P= 0.09).


CONCLUSIONS
Our results suggested no influence of the XRCC1 codon399 (Arg/Gln) and XPD codon751 (Lys/Gln) genetic polymorphisms on treatment response and survival in advanced NSCLC patients with platinum-based chemotherapy.
Yao
Cheng-Yun
CY
Department of Chemotherapy, Jiangsu Cancer Hospital and Research Institute, Nanjing, China.
Huang
Xin-En
XE
Li
Chao
C
Shen
Hong-Bing
HB
Shi
Mei-Qi
MQ
Feng
Ji-Feng
JF
Pan
Liang-Xi
LX
Tang
Jin-Hai
JH
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000556:secondary; D000328:Adult; D000368:Aged; D018287:Carcinoma, Large Cell / Q000188:drug therapy / Q000235:genetics / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000556:secondary; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000556:secondary; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011446:Prospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D000076105:X-ray Repair Cross Complementing Protein 1; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
D004268:DNA-Binding Proteins; D009944:Organoplatinum Compounds; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human