Polymorphisms of CAK genes and risk for lung cancer: a case-control study in Chinese population.
The incidence of lung cancer has been increasing over recent decades. Previous studies show that polymorphisms of the genes involved in carcinogen-detoxication, DNA repair and cell cycle control compose of the risk factors for lung cancer. Recent observations reveal that the components of CAK: Cdk7, MAT1 and cyclin H, may play important roles in cell cycle control, transcriptional control, and DNA repairing process, all of which are important in carcinogenesis. To test whether the genetic variants of CAK genes modify the risk of lung cancer, we compared the manifestation of 25 single nucleotide polymorphisms (SNPs) and the haplotypes of Cdk7, MAT1 and cyclin H between 500 patients with lung cancer and 517 healthy controls. Our results indicated that the genotype frequency of MAT1 79023A/G (p = 0.042) and MAT1 85693C/T (p = 0.005) of cases significantly differed from those of the controls. Further analyses revealed that cyclin H 11817C/T, MAT1 12199A/G, MAT1 70650A/G, MAT1 79023A/G and MAT1 85693C/T significantly influenced the susceptibility of lung cancer in a dominant genetic model while cyclin H 12128A/T and MAT1 42172A/G did in a recessive model. Strongest association between cyclin H alleles and lung cancer patients was found in the non-smoke subpopulation. The haplotype 'TAC' (p = 0.007) increased and the haplotype 'TTC' (p = 0.043) decreased the risk of lung cancer. The potential gene-gene and gene-environmental interactions on lung cancer risk was evaluated using MDR software. A significant interaction between the three CAK component genes was identified and the combination of smoking status and genetic factors barely increased the accuracy. Our results suggested that genetic variants in CAK genes, Cdk7, cyclin H, MAT1, might modulate the risk of lung cancer in a gene-gene interaction mode, which consist to the biochemical interaction of corresponding proteins.
Li
Yuanchun
Y
State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China.
Jin
Guangfu
G
Wang
Haifeng
H
Liu
Hongliang
H
Qian
Ji
J
Gu
Shaohua
S
Ma
Hongxia
H
Miao
Ruifeng
R
Hu
Zhibin
Z
Sun
Weiwei
W
Wang
Yi
Y
Jin
Li
L
Wei
Qingyi
Q
Shen
Hongbing
H
Huang
Wei
W
Lu
Daru
D
D044466:Asian People / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D018797:Cell Cycle Proteins; D002681:China; D056748:Cyclin H; D018844:Cyclin-Dependent Kinases / Q000235:genetics*; D016213:Cyclins / Q000235:genetics*; D004777:Environment; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012984:Software; D014157:Transcription Factors; D000095043:Cyclin-Dependent Kinase-Activating Kinase
C534751:CCNH protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D056748:Cyclin H; D016213:Cyclins; C514215:MNAT1 protein, human; D014157:Transcription Factors; D018844:Cyclin-Dependent Kinases; D000095043:Cyclin-Dependent Kinase-Activating Kinase; C000722416:CDK7 protein, human