title: Polymorphism rs7214723 in CAMKK1 and lung cancer risk in Chinese population.
abstract: Polymorphism rs7214723 was reported to be associated with lung cancer risk in UK Caucasians and caused the E375G substitution of CAMKK1 which plays important role in the calcium/calmodulin-dependent kinase cascade. To analyze rs7214723 in CAMKK1 and lung cancer risk in a Chinese population, SNPscan(TM) was used to genotype polymorphism rs7214723 in 961 lung cancer cases and 999 control subjects. The frequencies of the TT, TC, and CC genotypes of CAMKK1 rs7214723 were 43.3, 42.6, and 14.0 % in controls, and 41.1, 48.0, and 10.9 % in cases, respectively (P = 0.025). Compared with the CC genotype, TC genotype was associated with increased risk of lung cancer (OR 1.500, 95 % CI 1.112-2.022) after adjustment for age, gender, smoking status, and family history. The T allele of rs7214723 is the risk allele for lung carcinogenesis in dominant model (OR 1.354, 95 % CI 1.020-1.797). In stratified analysis, the risk effect of the TC genotype of rs7214723 was more evident in subgroups of those who had never been smokers (OR 1.556, 95 % CI 1.074-2.254). For the population without a family history of cancer, both the TT (OR 1.488, 95 % CI 1.050-2.109) and TC (OR 1.668, 95 % CI 1.180-2.357) carrier had an increased lung cancer risk. E375 is located in the kinase domain of CAMKK1, and E375G may change the electrical charge at the surface and decrease the kinase activity. Polymorphism rs7214723 in CAMKK1 might contribute to the risk of lung cancer in Chinese populations. The T allele is a risk allele in lung carcinogenesis.
authors.affiliation: Department of Oncology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
authors.forename: Yan-Hong
authors.initials: YH
authors.lastname: Zhang
authors.forename: Qing
authors.initials: Q
authors.lastname: Xu
authors.forename: Zhenhong
authors.initials: Z
authors.lastname: Zhao
authors.forename: Junjie
authors.initials: J
authors.lastname: Wu
authors.forename: Wei-Xing
authors.initials: WX
authors.lastname: Liu
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.forename: Jiu-Cun
authors.initials: JC
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics*; D000368:Aged; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase / Q000737:chemistry / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000235:genetics*; D016022:Case-Control Studies; D020134:Catalytic Domain; D002681:China; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D017422:Sequence Analysis, DNA
chemical_list: C517695:CAMKK1 protein, human; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase