The potentially functional polymorphism, rs31489, in the promoter region of cleft lip and palate transmembrane protein 1 (CLPTM1L) gene has been implicated in cancer risk. However, individual published studies showed inconclusive results. To obtain a more precise estimate of the association between CLPTM1L rs31489 and risk of lung cancer, we performed a meta-analysis. Summary odds ratios (ORs) and corresponding 95 % confidence intervals (CIs) were estimated using random-effects models. Ten individual case–control studies in eight publications with 20,680 cases and 28,330 controls were included. Overall, the variant genotypes were associated with a significantly increased lung cancer risk in different genetic models (CC + AC vs. AA: OR = 1.20, 95 % CI 1.12–1.28, P < 0.001; CC vs. AC + AA: OR = 1.15, 95 % CI 1.07–1.23, P < 0.001; CC vs. AA: OR = 1.28, 95 % CI 1.17–1.41, P < 0.001; CC vs. AC: OR = 1.11, 95 % CI 1.05–1.17, P < 0.001; C vs. A: OR = 1.12, 95 % CI 1.06–1.18, P < 0.001). In the stratified analyses, the increased lung risk remained for the studies of Caucasian populations. In conclusion, this meta-analysis suggested that CLPTM1L rs31489 was a potential biomarker for lung cancer risk in Caucasians.
Lung cancer CLPTM1L Meta-analysis Polymorphism
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This work was supported by the National Natural Science Foundation of China (No. 30900660, 81172227) and Science and Technology Commission of Shanghai Municipality (No. 09dz1976000, 124119a5800).
Yamamoto K, Okamoto A, Isonishi S, Ochiai K, Ohtake Y. A novel gene, CRR9, which was up-regulated in CDDP-resistant ovarian tumor cell line, was associated with apoptosis. Biochem Biophys Res Commun. 2001;280:1148–54.CrossRefPubMedGoogle Scholar
James MA, Wen W, Wang Y, Byers LA, Heymach JV, Coombes KR, et al. Functional characterization of CLPTM1L as a lung cancer risk candidate gene in the 5p15.33 locus. PLoS One. 2012;7:e36116.PubMedCentralCrossRefPubMedGoogle Scholar
Landi MT, Chatterjee N, Yu K, Goldin LR, Goldstein AM, Rotunno M, et al. A genome-wide association study of lung cancer identifies a region of chromosome 5p15 associated with risk for adenocarcinoma. Am J Hum Genet. 2009;85:679–91.PubMedCentralCrossRefPubMedGoogle Scholar
Pande M, Spitz MR, Wu X, Gorlov IP, Chen WV, Amos CI. Novel genetic variants in the chromosome 5p15.33 region associate with lung cancer risk. Carcinogenesis. 2011;32:1493–9.PubMedCentralCrossRefPubMedGoogle Scholar
Wauters E, Smeets D, Coolen J, Verschakelen J, De Leyn P, Decramer M, et al. The TERT-CLPTM1L locus for lung cancer predisposes to bronchial obstruction and emphysema. Eur Respir J. 2011;38:924–31.CrossRefPubMedGoogle Scholar
Bae EY, Lee SY, Kang BK, Lee EJ, Choi YY, Kang HG, et al. Replication of results of genome-wide association studies on lung cancer susceptibility loci in a Korean population. Respirology. 2012;17:699–706.CrossRefPubMedGoogle Scholar
Shiraishi K, Kunitoh H, Daigo Y, Takahashi A, Goto K, Sakamoto H, et al. A genome-wide association study identifies two new susceptibility loci for lung adenocarcinoma in the Japanese population. Nat Genet. 2012;44:900–3.CrossRefPubMedGoogle Scholar
de Mello RA, Ferreira M, Soares-Pires F, Costa S, Cunha J, Oliveira P, et al. The impact of polymorphic variations in the 5p15, 6p12, 6p21 and 15q25 loci on the risk and prognosis of Portuguese patients with non-small cell lung cancer. PLoS One. 2013;8:e72373.PubMedCentralCrossRefPubMedGoogle Scholar
Zhao Z, Li C, Yang L, Zhang X, Zhao X, Song X, et al. Significant association of 5p15.33 (TERT-CLPTM1L genes) with lung cancer in Chinese Han population. Exp Lung Res. 2013;39:91–8.CrossRefPubMedGoogle Scholar
James MA, Vikis HG, Tate E, Rymaszewski AL, You M. CRR9/CLPTM1L regulates cell survival signaling and is required for ras transformation and lung tumorigenesis. Cancer Res. 2013. doi:10.1158/0008-5472.CAN-13-1617.