Association of P53 and ATM Polymorphisms With Risk of Radiation-Induced Pneumonitis in Lung Cancer Patients Treated With Radiotherapy
- Departments of Etiology and Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China)
- Department of Radiation Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China)
Purpose: 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 and Materials: 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.
- OSTI ID:
- 21491676
- Journal Information:
- International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 5 Vol. 79; ISSN IOBPD3; ISSN 0360-3016
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
BODY
DISEASES
GENOTYPE
HAZARDS
HEALTH HAZARDS
INHIBITION
INJURIES
LUNGS
MEDICINE
NEOPLASMS
NUCLEAR MEDICINE
ORGANIC COMPOUNDS
ORGANS
PNEUMONITIS
PROTEINS
RADIATION EFFECTS
RADIATION HAZARDS
RADIATION INJURIES
RADIOLOGY
RADIOTHERAPY
RESPIRATORY SYSTEM
THERAPY