Polymorphisms in the apoptotic pathway gene BCL-2 and survival in small cell lung cancer.
BACKGROUND
We investigated the single-nucleotide polymorphism C-938A in the apoptotic gene BCL-2 to assess the potential impact as a genetic marker for response to chemotherapy and outcome prediction in small cell lung cancer (SCLC) patients. Such a marker might help optimize lung cancer treatment in a tailored approach.


METHODS
DNA derived from peripheral blood lymphocytes of 188 Caucasian SCLC patients treated at the Thoraxklinik Heidelberg was genotyped. Chemotherapy response, time to progression (TTP), and overall survival (OS) were evaluated using multivariable regression (unconditional logistic for response and Cox proportional hazard for TTP and OS) with odds ratios and hazard ratios (HRs) and their 95% confidence intervals (CIs) as quantitative outcome measures, respectively.


RESULTS
Small cell lung cancer patients carrying the BCL-2 -938CC genotype showed significantly worse TTP than patients carrying the BCL-2 -938AA genotype (HR = 1.86; 95% CI = 1.10-3.13, p = 0.021). The same adverse effect was shown for OS (HR = 2.38; 95% CI = 1.38-4.12, p = 0.002). Also, patients with limited disease (HR = 2.57; 95% CI = 1.18-5.60, p = 0.017) showed worse OS with the BCL-2 -938CC genotype.


CONCLUSIONS
BCL-2 -938CC genotype shows significantly worse outcome in small cell lung cancer patients. This genetic marker might particularly impact on treatment strategies using BCL-2 antisense approaches.
Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center, Heidelberg, Germany.
Lena Franziska
LF
Knoefel
Gisela
G
Werle-Schneider
Heike
H
Dally
Phillip Johannes
PJ
Müller
Lutz
L
Edler
Helmut
H
Bartsch
Siegfried
S
Tuengerthal
Claus Peter
CP
Heussel
Niels
N
Reinmuth
Michael
M
Thomas
Angela
A
Risch
D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D015996:Survival Rate
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D019253:Proto-Oncogene Proteins c-bcl-2