TP53 codon 72 polymorphism associated with prognosis in patients with advanced gastric cancer treated with paclitaxel and cisplatin.
OBJECTIVE
The present study analyzed the polymorphisms of apoptosis-related genes and their impact on the response to chemotherapy and survival of patients with advanced gastric cancer.


METHODS
Fifty-seven patients with advanced gastric cancer treated with paclitaxel and cisplatin combination chemotherapy were enrolled in the present study. The genomic DNA was extracted from paraffin-embedded tissue, and the single nucleotide polymorphisms (SNPs) of ten apoptosis-related genes [LTA, TP53, BCL2L11, BID, FASL, caspase 3, caspase 6, caspase 7, and caspase 9] determined using a polymerase chain reaction-restriction fragment length polymorphism assay.


RESULTS
The Arg/Pro and Pro/Pro genotypes of TP53 codon 72 were significantly correlated with a lower response rate to the combination chemotherapy when compared to the Arg/Arg genotype (35.7 vs. 66.7%, P-value 0.019) in a logistic regression analysis. A multivariate survival analysis also showed that the time to progression for the patients with the Arg/Pro and Pro/Pro genotypes of TP53 codon 72 was worse than for the patients with the Arg/Arg genotype (Hazard ratio = 3.056, P-value = 0.047), whereas the overall survival was not significantly different.


CONCLUSIONS
The TP53 codon 72 SNP was found to be predictive of the response to chemotherapy and correlate with the time to progression in patients with advanced gastric cancer treated with paclitaxel and cisplatin chemotherapy.
Kim
Jong Gwang
JG
Department of Oncology/Hematology, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, South Korea. jkk21c@knu.ac.kr
Sohn
Sang Kyun
SK
Chae
Yee Soo
YS
Song
Hong Suk
HS
Kwon
Ki-Young
KY
Do
Young Rok
YR
Kim
Min Kyoung
MK
Lee
Kyung Hee
KH
Hyun
Myung Soo
MS
Lee
Won Sik
WS
Sohn
Chang-Hak
CH
Jung
Joo Seop
JS
Kim
Gab Chul
GC
Chung
Ho Young
HY
Yu
Wansik
W
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000556:secondary; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003062:Codon / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D003062:Codon; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D017239:Paclitaxel; D002945:Cisplatin