Chemotherapy Effectiveness and Prognosis of Gastric Cancer Influenced by PTPN11 Polymorphisms.
OBJECTIVE
Since gastric cancer (GC) cells exhibited higher grades of SHP-2 encoded by PTPN11 than normal cells, it would be intriguing to explore whether PTPN11 single nucleotide polymorphisms (SNPs) would influence chemotherapy effectiveness and GC prognosis among a Chinese population.


METHODS
Altogether 430 late-stage GC patients and 960 healthy controls matched with age and sex were incorporated. Three PTPN11 SNPs (i.e. rs7958372, rs12229892 and rs2301756) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Chemotherapies of cisplatin and 5-fluorouracil were performed for 4 cycles. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the logistic regression. Survival curves were plotted with Kaplan-Meier method and the COX proportional hazard model was used to analyze independent factors for GC prognosis.


RESULTS
For rs12229892, AA and GA genotypes would cause 1.60-fold increase of GC risk in comparison to homozygote GG (OR = 1.60; 95% CI = 1.23-2.07; P < 0.001). The A allele of rs2301756 was significantly associated with a decrease in the risk of GC when compared with G allele (OR = 0.81; 95% CI = 0.65-0.99; P = 0.043). Results from both 2-cycle and 4-cycle chemotherapy suggested that chemotherapy was significantly more effective for GA and AA genotypes of rs2301756 compared with homozygote GG (P < 0.001). Besides, the joint impact of rs12229892 (AA) and environmental factors (i.e. smoking, family history, intake of processed food and H .pylori infection) on GC risk was considered as positive interaction, while that of rs2301756 (AA) and the above parameters was deemed as negative interaction. Finally, differentiation degree, axillary lymph node metastasis, rs12229892 and rs2301756 appeared as independent risk factors for GC development (all P < 0.05).


CONCLUSIONS
Since rs2301756 polymorphism of PTPN11 was associated with reduced risk of GC and better effects of chemotherapy on GC, it can be considered as a predictor of GC prognosis and the treatment target for GC.
Tianjin Anding Hospital, Tianjin, China.
Chuanjun
C
Zhuo
Mingjing
M
Shao
Ce
C
Chen
Chongguang
C
Lin
Deguo
D
Jiang
Guangdong
G
Chen
Hongjun
H
Tian
Lina
L
Wang
Jie
J
Li
Xiaodong
X
Lin
D000368:Aged; D000483:Alleles; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D002945:Cisplatin / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D015870:Gene Expression; D005787:Gene Frequency; D005838:Genotype; D016481:Helicobacter Infections / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics; D016480:Helicobacter pylori / Q000254:growth & development / Q000472:pathogenicity; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012150:Polymorphism, Restriction Fragment Length; D011379:Prognosis; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics*; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics; D016019:Survival Analysis; D016896:Treatment Outcome
D000970:Antineoplastic Agents; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D002945:Cisplatin; D005472:Fluorouracil