Association of P53 and ATM polymorphisms with risk of radiation-induced pneumonitis in lung cancer patients treated with radiotherapy.
OBJECTIVE
Radiation-induced pneumonitis (RP) is the most common dose-limiting complication in lung cancer patients treated with radiotherapy. Accumulating evidence indicates that P53 and the ataxia telangiectasia-mutated protein (ATM)-dependent signaling response cascade play a crucial role in radiation-induced diseases. Consistent with this, our previous study showed that a functional genetic ATM polymorphism was associated with increased RP risk.


METHODS
To evaluate the role of genetic P53 polymorphism in RP, we analyzed the P53 Arg72Pro polymorphism in a cohort including 253 lung cancer patients receiving thoracic irradiation.


RESULTS
We found that the P53 72Arg/Arg genotype was associated with increased RP risk compared with the 72Pro/Pro genotype. Furthermore, the P53 Arg72Pro and ATM -111G>A polymorphisms display an additive combination effect in intensifying the risk of developing RP. The cross-validation test showed that 63.2% of RP cases can be identified by P53 and ATM genotypes.


CONCLUSIONS
These results indicate that genetic polymorphisms in the ATM-P53 pathway influence susceptibility to RP and genotyping P53 and ATM polymorphisms might help to identify patients susceptible to developing RP when receiving radiotherapy.
Yang
Ming
M
Department of Etiology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Zhang
Li
L
Bi
Nan
N
Ji
Wei
W
Tan
Wen
W
Zhao
Lujun
L
Yu
Dianke
D
Wu
Chen
C
Wang
Luhua
L
Lin
Dongxin
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D064007:Ataxia Telangiectasia Mutated Proteins; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000532:radiotherapy; D018797:Cell Cycle Proteins / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011446:Prospective Studies; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D017564:Radiation Pneumonitis / Q000235:genetics*; D012044:Regression Analysis; D012306:Risk; D055752:Small Cell Lung Carcinoma / Q000235:genetics / Q000532:radiotherapy; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases