title: Functional genetic polymorphisms in PP2A subunit genes confer increased risks of lung cancer in southern and eastern Chinese.
abstract: Protein phosphatase-2A (PP2A) is one of the major cellular serine-threonine phosphatases and functions as a tumor suppressor that negatively regulates the activity of some oncogenic kinases. Recent studies have reported that PP2A expression was suppressed during lung carcinogenesis, we there hypothesized that the single nucleotide polymorphisms (SNPs) in PP2A subunit genes may affect PP2A function and thus contribute to lung cancer susceptibility. In a two-stage case-control study with a total of 1559 lung cancer patients and 1679 controls, we genotyped eight putative functional SNPs and one identified functional SNP (i.e., rs11453459) in seven major PP2A subunits (i.e., PPP2R1A, PPP2R1B, PPP2CA, PPP2R2A, PPP2R2B, PPP2R5C, PPP2R5E) in southern and eastern Chinese. We found that rs11453459G (-G/GG) variant genotypes of PPP2R1A and the rs1255722AA variant genotype of PPP2R5E conferred increased risks of lung cancer (rs11453459, -G/GG vs. -: OR = 1.31, 95% CI = 1.13-1.51; rs1255722, AA vs.
  OR = 1.27, 95% CI = 1.07-1.51). After combined the two variants, the number of the adverse genotypes was positively associated with lung cancer risk in a dose-response manner (P trend = 5.63 × 10(-6)). Further functional assay showed that lung cancer tissues carrying rs1255722AA variant genotype had a significantly lower mRNA level of PPP2R5E compared with tissues carrying GG/GA genotypes. However, such effect was not observed for the other SNPs and other combinations. Our findings suggested that the two functional variants in PPP2R1A and PPP2R5E and their combination are associated with lung cancer risk in Chinese, which may be valuable biomarkers to predict risk of lung cancer.
authors.affiliation: The Institute for Chemical Carcinogenesis, The State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou, China.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Yang
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.forename: Fuman
authors.initials: F
authors.lastname: Qiu
authors.forename: Lisha
authors.initials: L
authors.lastname: Zhang
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Yang
authors.forename: Jieqiong
authors.initials: J
authors.lastname: Deng
authors.forename: Wenxiang
authors.initials: W
authors.lastname: Fang
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Zhou
authors.forename: Jiachun
authors.initials: J
authors.lastname: Lu
mesh_terms: D000230:Adenocarcinoma / Q000208:ethnology / Q000235:genetics*; D000368:Aged; D000483:Alleles; D044466:Asian People; D014408:Biomarkers, Tumor / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008175:Lung Neoplasms / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D054648:Protein Phosphatase 2 / Q000235:genetics*; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; C517191:PPP2R1A protein, human; C525692:PPP2R5E protein, human; D054648:Protein Phosphatase 2