Polymorphisms in the CASPASE Genes and Survival in Patients With Early-Stage Non-Small-Cell Lung Cancer
JOURNAL OF CLINICAL ONCOLOGY
Authors: Yoo, Seung Soo; Choi, Jin Eun; Lee, Won-Kee; Choi, Yi-Young; Kam, Sin; Kim, Min Jung; Jeon, Hyo-Sung; Lee, Eung-Bae; Kim, Dong Sun; Lee, Myung-Hoon; Kim, In-San; Jheon, Sanghoon; Park, Jae Yong
Abstract
Purpose This study was conducted to determine the impact of potentially functional polymorphisms in the CASPASE ( CASP) genes on the survival of early-stage non-small-cell lung cancer (NSCLC) patients. Patients and Methods Four hundred eleven consecutive patients with surgically resected NSCLC were enrolled. Nine potentially functional polymorphisms in the CASP3, CASP7, CASP8, CASP9, and CASP10 genes were investigated. The genotype and haplotype associations with overall survival ( OS) and disease-free survival (DFS) were analyzed. Results Patients with the rs2227310 GG genotype had a significantly decreased OS and DFS compared with patients with the CC + CG genotype (adjusted hazard ratio [aHR] for OS, 1.67; 95% CI, 1.19 to 2.35; P = .003; aHR for DFS, 1.62; 95% CI, 1.19 to 2.22; P = .002). The rs4645981C > T genotype also had a significant effect on OS and DFS ( under a recessive model; aHR for OS, 2.00; 95% CI, 1.04 to 3.85; P = .04; aHR for DFS, 2.76; 95% CI, 1.58 to 4.80; P = .0003). When the rs2227310 and rs4645981 genotypes were combined, patients with one or two bad genotypes had worse OS and DFS compared with those who had zero bad genotypes (aHR for OS, 1.75; 95% CI, 1.25 to 2.45; P = .001; aHR for DFS, 1.66; 95% CI, 1.23 to 2.26; P = .001). Conclusion The CASP7 rs2227310 and CASP9 rs4645981 polymorphisms may affect survival in early-stage NSCLC. The analysis of these polymorphisms can help identify patients at high risk for a poor disease outcome.
Caspase 8 and caspase 9 gene polymorphisms and susceptibility to gastric cancer
GASTRIC CANCER
Authors: Liamarkopoulos, Emmanouil; Gazouli, Maria; Aravantinos, Gerasimos; Tzanakis, Nikolaos; Theodoropoulos, George; Rizos, Spyros; Nikiteas, Nikolaos
Abstract
Caspase-8 (CASP8) and caspase-9 (CASP9) play crucial roles in regulating apoptosis, and their functional polymorphisms may alter cancer risk. Our aim was to investigate the association of CASP8 and CASP9 gene polymorphisms with gastric cancer (GC) susceptibility. We undertook a case-control study of 88 GC cases and 480 controls to investigate the association between CASP8 -652 6N ins/del and CASP9 -1263 A > G polymorphisms and GC susceptibility by a polymerase chain reaction (PCR)-restriction fragment length polymorphism method. CASP8 -652 6N ins/del polymorphism and CASP9 -1263 GG genotype were observed to be significantly associated with a reduced risk of GC. No significant association was observed between CASP8 -652 6N ins/del and CASP9 -1263 A > G polymorphisms and tumor characteristics. However, both CASP8 del/del and CASP9 -1263 GG genotypes were associated with increased overall survival in GC patients. The CASP8 -652 6N ins/del and the CASP9 -1263 A > G polymorphisms were observed to play a protective role in GC predisposition.