Polymorphisms in the caspase genes and the risk of lung cancer.
BACKGROUND
Caspases (CASPs) are important regulators and executioners in apoptosis pathway and play a crucial role in the development and progression of cancer. On the basis of the interactions of CASPs in the apoptotic pathway, we evaluated the association between 11 polymorphisms of CASP3, 6, 7, 8, 9, and 10 genes and the risk of lung cancer.


METHODS
The genotypes were determined in 720 patients with lung cancer and 720 healthy controls frequency matched for age and gender.


RESULTS
In individual polymorphism analysis, the CASP7 rs2227310C>G and CASP9 rs4645981C>T were associated with 1.40-fold and 1.28-fold increased risk of lung cancer under recessive and dominant models for the variant allele of each polymorphism, respectively. In the case of the CASP3 77G>A, subjects with the GG genotype were at a 1.19-fold increased risk of lung cancer compared with those with at least one variant allele. When the three polymorphisms were combined, the risk of lung cancer increased in a dose-dependent manner as the number of risk genotypes increased (ptrend <0.001). Subjects with two and three risk genotypes carried a significantly increased risk of lung cancer compared with those with zero risk genotype (adjusted odds ratio = 1.56, 95% confidence interval = 1.14-2.13, p = 0.005 and adjusted odds ratio = 2.54, 95% confidence interval = 1.28-5.02, p = 0.008, respectively).


CONCLUSIONS
These results suggest that a combined analysis of these three CASP gene polymorphisms might better predict the risk of lung cancer than analysis of a single polymorphism.
Lee
Shin Yup
SY
Department of Internal Medicine, Kyungpook National University Hospital, Samduk 2Ga 50, Daegu 700-412, Republic of Korea.
Choi
Yi Young
YY
Choi
Jin Eun
JE
Kim
Min Jung
MJ
Kim
Jong-Sik
JS
Jung
Deuk Kju
DK
Kang
Hyo-Gyoung
HG
Jeon
Hyo-Sung
HS
Lee
Won Kee
WK
Jin
Guang
G
Cha
Seung Ick
SI
Kim
Chang Ho
CH
Jung
Tae Hoon
TH
Park
Jae Yong
JY
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D018287:Carcinoma, Large Cell / Q000235:genetics / Q000473:pathology; D016022:Case-Control Studies; D053148:Caspase 3 / Q000235:genetics*; D053179:Caspase 7 / Q000235:genetics*; D053453:Caspase 9 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018307:Neoplasms, Squamous Cell / Q000235:genetics / Q000473:pathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors; D055752:Small Cell Lung Carcinoma / Q000235:genetics / Q000473:pathology; D015996:Survival Rate
C505407:CASP3 protein, human; C505520:CASP7 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053179:Caspase 7; D053453:Caspase 9