Effect of the BCL2 gene polymorphism on survival in advanced-stage non-small cell lung cancer patients who received chemotherapy.
BACKGROUND
This study aimed to evaluate the association between BCL2 single-nucleotide polymorphisms and survival outcome in advanced non-small cell lung cancer (NSCLC).


METHODS
One hundred and sixty-eight patients with advanced NSCLC who were treated with anti-cancer drugs and could be evaluated for therapeutic response between April 2005 and March 2010 at Kyoto University Hospital were enrolled. DNA was extracted from peripheral blood samples. The BCL2 polymorphisms -938 C→A (rs2279115) and +21 A→G (rs1801018) were genotyped using the 5'-nuclease assay. The univariate relationship between each independent clinicopathologic variable and BCL2 genotype was examined using Fisher's exact test. To evaluate risk factors associated with prognosis, a Cox proportional hazards regression model with a step-down procedure was used.


RESULTS
The median survival time of patients with the -938 AA and AC genotypes were significantly shorter than those with the -938 CC genotype (p = 0.027 by log-rank test). Based on multivariate analysis, poor performance status [hazard ratio (HR) 2.424, 95% confidence interval (CI) 1.727-3.262; p < 0.0001], non-adenocarcinoma histology (HR 1.512, 95% CI 1.167-1.938; p = 0.0048) and the BCL2 -938 AA + AC genotype (HR 1.219, 95% CI, 1.024-1.456; p = 0.0256) were significant independent prognostic factors for survival.


CONCLUSIONS
Polymorphisms in BCL2 may be associated with survival in advanced-stage NSCLC patients who received chemotherapy.
Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan. masago@kuhp.kyoto-u.ac.jp
Katsuhiro
K
Masago
Yosuke
Y
Togashi
Shiro
S
Fujita
Hiroki
H
Nagai
Yuichi
Y
Sakamori
Chiyuki
C
Okuda
Young Hak
YH
Kim
Michiaki
M
Mishima
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2