Identification of polymorphisms in the Caspase-3 gene and their association with lung cancer risk.
Caspase-3 (CASP-3) is a primary effector CASP that executes programmed cell death, and it plays an important role in the development and progression of cancer. Polymorphisms in the CASP-3 gene may influence CASP-3 production and/or activity, thereby modulating the susceptibility to lung cancer. To test this hypothesis, we first screened for polymorphisms in the CASP-3 gene by direct sequencing of genomic DNA samples from 27 healthy Koreans, and then evaluated their associations with lung cancer in a case-control study that consisted of 582 lung cancer patients and 582 healthy controls. Individuals with at least one variant allele of the -928A > G, 77G > A, and 17532A > C polymorphisms were at a significantly decreased risk for lung cancer in comparison to the carriers with each homozygous wild-type allele [adjusted odds ratio (OR) = 0.79, 95% confidence interval (CI) = 0.62-1.00, P = 0.05; adjusted OR = 0.78, 95% CI = 0.61-0.99, P = 0.04; and adjusted OR = 0.74, 95% CI = 0.58-0.95, P = 0.02, respectively]. Consistent with the results of genotyping analysis, the GAGC haplotype carrying the variant allele at all of the -928A > G, 77G > A, and 17532A > C loci was associated with a significantly decreased risk of lung cancer compared to the AGGA haplotype carrying no variant alleles at the three loci (adjusted OR = 0.66, 95% CI = 0.51-0.86, P = 0.002 and Bonferroni corrected P = 0.008). These results suggest that the CASP-3 polymorphisms and their haplotypes contribute to the genetic susceptibility to lung cancer.
Department of Biochemistry, School of Medicine, Kyungpook National University, Daegu, Korea.
Jin Sung
JS
Jang
Kyung Mee
KM
Kim
Jin Eun
JE
Choi
Sung Ick
SI
Cha
Chang Ho
CH
Kim
Won Kee
WK
Lee
Sin
S
Kam
Tae Hoon
TH
Jung
Jae Yong
JY
Park
D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics / Q000556:secondary; D018288:Carcinoma, Small Cell / Q000235:genetics / Q000473:pathology / Q000556:secondary; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics / Q000556:secondary; D016022:Case-Control Studies; D053148:Caspase 3 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007723:Korea / Q000453:epidemiology; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking
D053148:Caspase 3