Clinical significance of NQO1 C609T polymorphisms after postoperative radiation therapy in completely resected non-small cell lung cancer.
OBJECTIVE
To investigate the clinical significance of NQO1 C609T polymorphisms to treatment outcome after postoperative radiation therapy in completely resected non-small cell lung cancer (NSCLC).


METHODS
One hundred and sixteen, Korean-ethnic, patients who were treated with surgery and postoperative radiation therapy from February 2000 to September 2005 in Asan Medical Center (Seoul, South Korea) were analyzed. All patients received 5040cGy radiation to surgical stump, mediastinum and ipsilateral supraclavicular node. NQO1 C609T polymorphisms were examined from a peripheral blood sample in all patients. Three types of NQO1 C609T polymorphisms were designated as C/C, C/T and T/T. Chest computed tomography was routinely checked after radiation therapy at every 3 or 6 months and locoregional tumor control, distant metastasis and survival by NQO1 C609T genotype were analyzed.


RESULTS
The proportion of NQO1 C609T polymorphisms was 27.6% for C/C, 53.4% for C/T and 19.0% for T/T. Most patients were men and had squamous cell carcinoma or adenocarcinoma. Median age of patients was 61 years. Major failure pattern was distant metastasis and 13 (11.2%) patients showed locoregional recurrence within the field of previous radiation therapy. Crude locoregional recurrence rate was significantly different by NQO1 genotype; 6.3% in C/C, 8.1% in C/T, and 27.3% in T/T (p=0.03), but distant metastasis was not different. Median follow-up time was 49.2 months (range: 3.4-103.5 months). Locoregional recurrence-free survival (LRRFS) was affected in T/T genotype compared with C/C or C/T genotype (p=0.01, Kaplan-Meier method), but distant metastasis-free survival (DMFS) or overall survival (OS) was not different by NQO1 genotype in univariate analysis. NQO1 genotype was also a significant factor for LRRFS (p=0.01) in multivariate analysis. Radiation-induced pneumonitis or esophagitis was tolerable in all patients and the difference by NQO1 genotype was not observed.


CONCLUSIONS
NQO1 C609T polymorphisms could be a predictive factor for the locoregional tumor control after postoperative radiation therapy in completely resected NSCLC.
Song
Si Yeol
SY
Department of Radiation Oncology, Asan Medical Center, College of Medicine, University of Ulsan, 388-1 Pungnap-2dong, Songpa-gu, Seoul, Republic of Korea.
Jeong
Seong-Yun
SY
Park
Heon Joo
HJ
Park
Seung-Il
SI
Kim
Dong Kwan
DK
Kim
Yong Hee
YH
Shin
Seong Soo
SS
Lee
Sang-Wook
SW
Ahn
Seung Do
SD
Kim
Jong Hoon
JH
Lee
Jung Shin
JS
Choi
Eun Kyung
EK
D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics* / Q000378:metabolism; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D011013:Pneumonectomy; D011110:Polymorphism, Genetic; D011182:Postoperative Care; D011379:Prognosis; D013902:Radiography, Thoracic; D018714:Radiotherapy, Adjuvant; D056910:Republic of Korea; D016896:Treatment Outcome
D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human