Association of PSMA4 polymorphisms with lung cancer susceptibility and response to cisplatin-based chemotherapy in a Chinese Han population.
OBJECTIVE
Genetic factors play an important role in our predisposition to cancer. Genome-wide association studies have linked the chromosome 15q25.1 locus to lung cancer susceptibility and implicated proteasome subunit alpha type-4 (PSMA4) as a candidate gene. In this case-control study, pathologically confirmed lung cancer patients and controls from the Chinese Han population were investigated to determine the effect of variant genotypes within the PSMA4 locus on susceptibility to lung cancer and sensitivity to cisplatin-based chemotherapy.


METHODS
We identified validated tagged single nucleotide polymorphisms (tSNPs) with minor allele frequency >5 % in the HapMap Chinese Han Beijing population and genotyped seven SNPs within the PSMA4 locus. Their correlation with lung cancer risks and treatment response were examined using χ (2) test and haplotype analysis. Multivariate logistic regression analysis tested the association between the polymorphisms and chemotherapy response.


RESULTS
rs12901682 is associated with lung cancer risks (OR = 1.45, 95 % CI, 1.04-2.02; P = 0.029). Using SNPStats software, we found rs12901682 (OR = 6.30, 95 % CI, 1.31-30.26; P = 0.0073) associated with lung cancer risks in the recessive model. Haplotype analysis showed that "CAGAATC" conferred an increased risk of lung cancer (OR = 1.50, 95 % CI, 1.07-2.11; P = 0.019). After adjustment for age, this association was pronounced in the male gender (OR = 6.30, 95 % CI, 1.31-30.26; P = 0.0073). PSMA4 polymorphisms did not affect the tumor sensitivity to cisplatin combination chemotherapy.


CONCLUSIONS
Our study suggests a potential association between PSMA4 variants and lung cancer risk in Chinese Han population.
Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Medical College of Xian Jiaotong University, 277 Yanta West Road, Xi'an, 710061, Shaanxi Province, People's Republic of China.
T
T
Wang
T
T
Chen
A
A
Thakur
Y
Y
Liang
L
L
Gao
S
S
Zhang
Y
Y
Tian
T
T
Jin
J J
JJ
Liu
M
M
Chen
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics*; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D044466:Asian People / Q000235:genetics*; D018287:Carcinoma, Large Cell / Q000188:drug therapy / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics*; D016022:Case-Control Studies; D002945:Cisplatin / Q000627:therapeutic use; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D046988:Proteasome Endopeptidase Complex / Q000235:genetics*; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy / Q000235:genetics*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; C000593243:PSMA4 protein, human; D046988:Proteasome Endopeptidase Complex; D002945:Cisplatin