Abstract
The association between common variations (rs10937405, rs4488809) on 3q28 and lung cancer has been widely evaluated in various ethnic groups, since it was first identified through genome-wide association approach. However, the results have been inconclusive. To derive a more precise estimation of the relationship and the effect of factors that might modify the risk, we performed this meta-analysis. The random-effects model was applied, addressing heterogeneity and publication bias. A total of 10 articles involving 36,221 cases and 58,108 controls were included. Overall, the summary per-allele OR of 1.19 (95 % CI 1.14–1.25, P < 10−5) and 1.17 (95 % CI 1.10–1.23, P < 10−5) was found for the rs10937405 and rs4488809 polymorphisms, respectively. Significant results were also observed in heterozygous and homozygous when compared with wild genotype for these polymorphisms. Significant results were found in East Asians when stratified by ethnicity, whereas no significant associations were found among Caucasians. After stratifying by sample size, study design, control source and sex, significant associations were also obtained. In addition, our data indicate that these polymorphisms are involved in lung cancer susceptibility and confer its effect primarily in lung adenocarcinoma when stratified by histological subtype. Furthermore, significant associations were also detected both never-smokers and smokers for these polymorphisms. In conclusion, this meta-analysis demonstrated that rs10937405 and rs4488809 are a risk factor associated with increased non-small cell lung cancer susceptibility, particularly for East Asian populations.
Similar content being viewed by others
References
Amos CI, Wu X, Broderick P, Gorlov IP, Gu J, Eisen T, Dong Q, Zhang Q, Gu X, Vijayakrishnan J, Sullivan K, Matakidou A, Wang Y, Mills G, Doheny K, Tsai YY, Chen WV, Shete S, Spitz MR, Houlston RS (2008) Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1. Nat Genet 40:616–622
Broderick P, Wang Y, Vijayakrishnan J, Matakidou A, Spitz MR, Eisen T, Amos CI, Houlston RS (2009) Deciphering the impact of common genetic variation on lung cancer risk: a genome-wide association study. Cancer Res 69:6633–6641
Chen Z, Li Z, Niu X, Ye X, Yu Y, Lu S, Chen Z (2011) The effect of CYP1A1 polymorphisms on the risk of lung cancer: a global meta-analysis based on 71 case–control studies. Mutagenesis 26:437–446
Cochran WG (1954) The combination of estimates from different experiments. Biometrics 10:101–129
Daigo Y, Nakamura Y (2008) From cancer genomics to thoracic oncology: discovery of new biomarkers and therapeutic targets for lung and esophageal carcinoma. Gen Thorac Cardiovasc Surg 56:43–53
DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188
Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634
Essick EE, Sam F (2010) Oxidative stress and autophagy in cardiac disease, neurological disorders, aging and cancer. Oxid Med Cell Longev 3:168–177
Flores ER (2007) The roles of p63 in cancer. Cell Cycle 6:300–304
Hecht SS (1999) Tobacco smoke carcinogens and lung cancer. J Natl Cancer Inst 91:1194–1210
Hecht SS (2002) Cigarette smoking and lung cancer: chemical mechanisms and approaches to prevention. Lancet Oncol 3:461–469
Hemminki K, Lorenzo Bermejo J, Försti A (2006) The balance between heritable and environmental aetiology of human disease. Nat Rev Genet 7:958–965
Hirschhorn JN, Lohmueller K, Byrne E (2002) A comprehensive review of genetic association studies. Genet Med 4:45–61
Hosgood HD 3rd, Wang WC, Hong YC, Wang JC, Chen K, Chang IS, Chen CJ, Lu D, Yin Z, Wu C, Zheng W, Qian B, Park JY, Kim YH, Chatterjee N, Chen Y, Chang GC, Hsiao CF, Yeager M, Tsai YH, Wei H, Kim YT, Wu W, Zhao Z, Chow WH, Zhu X, Lo YL, Sung SW, Chen KY, Yuenger J, Kim JH, Huang L, Chen YH, Gao YT, Kim JH, Huang MS, Jung TH, Caporaso N, Zhao X, Huan Z, Yu D, Kim CH, Su WC, Shu XO, Kim IS, Bassig B, Chen YM, Cha SI, Tan W, Chen H, Yang TY, Sung JS, Wang CL, Li X, Park KH, Yu CJ, Ryu JS, Xiang Y, Hutchinson A, Kim JS, Cai Q, Landi MT, Lee KM, Hung JY, Park JY, Tucker M, Lin CC, Ren Y, Perng RP, Chen CY, Jin L, Chen KC, Li YJ, Chiu YF, Tsai FY, Yang PC, Fraumeni JF Jr, Seow A, Lin D, Zhou B, Chanock S, Hsiung CA, Rothman N, Lan Q (2012) Genetic variant in TP63 on locus 3q28 is associated with risk of lung adenocarcinoma among never-smoking females in Asia. Hum Genet 131:1197–1203
Hu Z, Wu C, Shi Y, Guo H, Zhao X, Yin Z, Yang L, Dai J, Hu L, Tan W, Li Z, Deng Q, Wang J, Wu W, Jin G, Jiang Y, Yu D, Zhou G, Chen H, Guan P, Chen Y, Shu Y, Xu L, Liu X, Liu L, Xu P, Han B, Bai C, Zhao Y, Zhang H, Yan Y, Ma H, Chen J, Chu M, Lu F, Zhang Z, Chen F, Wang X, Jin L, Lu J, Zhou B, Lu D, Wu T, Lin D, Shen H (2011) A genome-wide association study identifies two new lung cancer susceptibility loci at 13q12.12 and 22q12.2 in Han Chinese. Nat Genet 43:792–796
Hu QY, Jin TB, Wang L, Zhang L, Geng T, Liang G, Kang LL (2014) Genetic variation in the TP63 gene is associated with lung cancer risk in the Han population. Tumour Biol 35:1863–1866
Hung RJ, McKay JD, Gaborieau V, Boffetta P, Hashibe M, Zaridze D, Mukeria A, Szeszenia-Dabrowska N, Lissowska J, Rudnai P, Fabianova E, Mates D, Bencko V, Foretova L, Janout V, Chen C, Goodman G, Field JK, Liloglou T, Xinarianos G, Cassidy A, McLaughlin J, Liu G, Narod S, Krokan HE, Skorpen F, Elvestad MB, Hveem K, Vatten L, Linseisen J, Clavel-Chapelon F, Vineis P, Bueno-de-Mesquita HB, Lund E, Martinez C, Bingham S, Rasmuson T, Hainaut P, Riboli E, Ahrens W, Benhamou S, Lagiou P, Trichopoulos D, Holcátová I, Merletti F, Kjaerheim K, Agudo A, Macfarlane G, Talamini R, Simonato L, Lowry R, Conway DI, Znaor A, Healy C, Zelenika D, Boland A, Delepine M, Foglio M, Lechner D, Matsuda F, Blanche H, Gut I, Heath S, Lathrop M, Brennan P (2008) A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25. Nature 452:633–637
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90
Jorgensen ED, Zhao H, Traganos F, Albino AP, Darzynkiewicz Z (2010) DNA damage response induced by exposure of human lung adenocarcinoma cells to smoke from tobacco- and nicotine-free cigarettes. Cell Cycle 9:2170–2176
Katoh I, Aisaki KI, Kurata SI, Ikawa S, Ikawa Y (2000) p51A (TAp63gamma), a p53 homolog, accumulates in response to DNA damage for cell regulation. Oncogene 19:3126–3130
Lan Q, Hsiung CA, Matsuo K, Hong YC, Seow A, Wang Z, Hosgood HD 3rd, Chen K, Wang JC, Chatterjee N, Hu W, Wong MP, Zheng W, Caporaso N, Park JY, Chen CJ, Kim YH, Kim YT, Landi MT, Shen H, Lawrence C, Burdett L, Yeager M, Yuenger J, Jacobs KB, Chang IS, Mitsudomi T, Kim HN, Chang GC, Bassig BA, Tucker M, Wei F, Yin Z, Wu C, An SJ, Qian B, Lee VH, Lu D, Liu J, Jeon HS, Hsiao CF, Sung JS, Kim JH, Gao YT, Tsai YH, Jung YJ, Guo H, Hu Z, Hutchinson A, Wang WC, Klein R, Chung CC, Oh IJ, Chen KY, Berndt SI, He X, Wu W, Chang J, Zhang XC, Huang MS, Zheng H, Wang J, Zhao X, Li Y, Choi JE, Su WC, Park KH, Sung SW, Shu XO, Chen YM, Liu L, Kang CH, Hu L, Chen CH, Pao W, Kim YC, Yang TY, Xu J, Guan P, Tan W, Su J, Wang CL, Li H, Sihoe AD, Zhao Z, Chen Y, Choi YY, Hung JY, Kim JS, Yoon HI, Cai Q, Lin CC, Park IK, Xu P, Dong J, Kim C, He Q, Perng RP, Kohno T, Kweon SS, Chen CY, Vermeulen R, Wu J, Lim WY, Chen KC, Chow WH, Ji BT, Chan JK, Chu M, Li YJ, Yokota J, Li J, Chen H, Xiang YB, Yu CJ, Kunitoh H, Wu G, Jin L, Lo YL, Shiraishi K, Chen YH, Lin HC, Wu T, Wu YL, Yang PC, Zhou B, Shin MH, Fraumeni JF Jr, Lin D, Chanock SJ, Rothman N (2012) Genome-wide association analysis identifies new lung cancer susceptibility loci in never-smoking women in Asia. Nat Genet 44:1330–1335
Lee JM, Yanagawa J, Peebles KA, Sharma S, Mao JT, Dubinett SM (2008) Inflammation in lung carcinogenesis: new targets for lung cancer chemoprevention and treatment. Crit Rev Oncol Hematol 66:208–217
Li D, He L (2008) Meta-study on association between the monoamine oxidase A gene (MAOA) and schizophrenia. Am J Med Genet B Neuropsychiatr Genet 147B:174–178
Li Y, Huang Y, Cao YS, Zeng J, Tong WN, Xu SL, Zhuo AS (2013) Assessment of the association between XRCC1 Arg399Gln polymorphism and lung cancer in Chinese. Tumour Biol 34:3681–3685
Lin YL, Sengupta S, Gurdziel K, Bell GW, Jacks T, Flores ER (2009) p63 and p73 transcriptionally regulate genes involved in DNA repair. PLoS Genet 5:e1000680
Liu G, Zhou W, Christiani DC (2005) Molecular epidemiology of non-small cell lung cancer. Semin Respir Crit Care Med 26:265–272
Lohmueller KE, Pearce CL, Pike M, Lander ES, Hirschhorn JN (2003) Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease. Nat Genet 33:177–182
Maiuri MC, Tasdemir E, Criollo A, Morselli E, Vicencio JM, Carnuccio R, Kroemer G (2009) Control of autophagy by oncogenes and tumor suppressor genes. Cell Death Differ 16:87–93
Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22:719–748
McKay JD, Hung RJ, Gaborieau V, Boffetta P, Chabrier A, Byrnes G, Zaridze D, Mukeria A, Szeszenia-Dabrowska N, Lissowska J, Rudnai P, Fabianova E, Mates D, Bencko V, Foretova L, Janout V, McLaughlin J, Shepherd F, Montpetit A, Narod S, Krokan HE, Skorpen F, Elvestad MB, Vatten L, Njølstad I, Axelsson T, Chen C, Goodman G, Barnett M, Loomis MM, Lubiñski J, Matyjasik J, Lener M, Oszutowska D, Field J, Liloglou T, Xinarianos G, Cassidy A; EPIC Study, Vineis P, Clavel-Chapelon F, Palli D, Tumino R, Krogh V, Panico S, González CA, Ramón Quirós J, Martínez C, Navarro C, Ardanaz E, Larrañaga N, Kham KT, Key T, Bueno-de-Mesquita HB, Peeters PH, Trichopoulou A, Linseisen J, Boeing H, Hallmans G, Overvad K, Tjønneland A, Kumle M, Riboli E, Zelenika D, Boland A, Delepine M, Foglio M, Lechner D, Matsuda F, Blanche H, Gut I, Heath S, Lathrop M, Brennan P (2008) Lung cancer susceptibility locus at 5p15.33. Nat Genet 40:1404–1406
Melino G (2011) p63 is a suppressor of tumorigenesis and metastasis interacting with mutant p53. Cell Death Differ 18:1487–1499
Miki D, Kubo M, Takahashi A, Yoon KA, Kim J, Lee GK, Zo JI, Lee JS, Hosono N, Morizono T, Tsunoda T, Kamatani N, Chayama K, Takahashi T, Inazawa J, Nakamura Y, Daigo Y (2010) Variation in TP63 is associated with lung adenocarcinoma susceptibility in Japanese and Korean populations. Nat Genet 42:893–896
Moll UM, Slade N (2004) p63 and p73: roles in development and tumor formation. Mol Cancer Res 2:371–386
Pan Y, Wang F, Qiu Q, Ding R, Zhao B, Zhou H (2013) Influence of the Angiotensin converting enzyme insertion or deletion genetic variant and coronary restenosis risk: evidence based on 11,193 subjects. PLoS One 8:e83415
Petitjean A, Ruptier C, Tribollet V, Hautefeuille A, Chardon F, Cavard C, Puisieux A, Hainaut P, Caron de Fromentel C (2008) Properties of the six isoforms of p63: p53-like regulation in response to genotoxic stress and cross talk with DeltaNp73. Carcinogenesis 29:273–281
Ratovitski EA (2010) LKB1/PEA3/ΔNp63 pathway regulates PTGS-2 (COX-2) transcription in lung cancer cells upon cigarette smoke exposure. Oxid Med Cell Longev 3:317–324
Risch N, Merikangas K (1996) The future of genetic studies of complex human diseases. Science 273:1516–1517
Shiraishi K, Kunitoh H, Daigo Y, Takahashi A, Goto K, Sakamoto H, Ohnami S, Shimada Y, Ashikawa K, Saito A, Watanabe S, Tsuta K, Kamatani N, Yoshida T, Nakamura Y, Yokota J, Kubo M, Kohno T (2012) A genome-wide association study identifies two new susceptibility loci for lung adenocarcinoma in the Japanese population. Nat Genet 44:900–903
Sun S, Schiller JH, Gazdar AF (2007) Lung cancer in never smokers-a different disease. Nat Rev Cancer 7:778–790
Tang K, Li Y, Zhang Z, Gu Y, Xiong Y, Feng G, He L, Qin S (2010) The PstI/RsaI and DraI polymorphisms of CYP2E1 and head and neck cancer risk: a meta-analysis based on 21 case-control studies. BMC Cancer 10:575
Taylor SJ, Tweedie RI (1998) Practical estimates of the effect of publication bias in meta-analysis. Australas Epidemiol 5:14–17
Thompson SG, Sharp SJ (1999) Explaining heterogeneity in meta-analysis: a comparison of methods. Stat Med 18:2693–2708
Timofeeva MN, Hung RJ, Rafnar T, Christiani DC, Field JK, Bickeböller H, Risch A, McKay JD, Wang Y, Dai J, Gaborieau V, McLaughlin J, Brenner D, Narod SA, Caporaso NE, Albanes D, Thun M, Eisen T, Wichmann HE, Rosenberger A, Han Y, Chen W, Zhu D, Spitz M, Wu X, Pande M, Zhao Y, Zaridze D, Szeszenia-Dabrowska N, Lissowska J, Rudnai P, Fabianova E, Mates D, Bencko V, Foretova L, Janout V, Krokan HE, Gabrielsen ME, Skorpen F, Vatten L, Njølstad I, Chen C, Goodman G, Lathrop M, Benhamou S, Vooder T, Välk K, Nelis M, Metspalu A, Raji O, Chen Y, Gosney J, Liloglou T, Muley T, Dienemann H, Thorleifsson G, Shen H, Stefansson K, Brennan P, Amos CI, Houlston R, Landi MT; Transdisciplinary Research in Cancer of the Lung (TRICL) Research Team (2012) Influence of common genetic variation on lung cancer risk: meta-analysis of 14 900 cases and 29 485 controls. Hum Mol Genet 21:4980–4995
Tokuhata GK, Lilienfeld AM (1963) Familial aggregation of lung cancer in humans. J Natl Cancer Inst 30:289–312
Tomkova K, Tomka M, Zajac V (2008) Contribution of p53, p63, and p73 to the developmental diseases and cancer. Neoplasma 55:177–181
Vineis P, Alavanja M, Buffler P, Fontham E, Franceschi S, Gao YT, Gupta PC, Hackshaw A, Matos E, Samet J, Sitas F, Smith J, Stayner L, Straif K, Thun MJ, Wichmann HE, Wu AH, Zaridze D, Peto R, Doll R (2004) Tobacco and cancer: recent epidemiological evidence. J Natl Cancer Inst 96:99–106
Vousden KH, Prives C (2009) Blinded by the light: the growing complexity of p53. Cell 137:413–431
Wang Y, Broderick P, Webb E, Wu X, Vijayakrishnan J, Matakidou A, Qureshi M, Dong Q, Gu X, Chen WV, Spitz MR, Eisen T, Amos CI, Houlston RS (2008) Common 5p15.33 and 6p21.33 variants influence lung cancer risk. Nat Genet 40:1407–1409
Wang Y, Broderick P, Matakidou A, Vijayakrishnan J, Eisen T, Houlston RS (2011) Variation in TP63 is associated with lung adenocarcinoma in the UK population. Cancer Epidemiol Biomarkers Prev 20:1453–1462
Ye Z, Song H, Higgins JP, Pharoah P, Danesh J (2006) Five glutathione s-transferase gene variants in 23,452 cases of lung cancer and 30,397 controls: meta-analysis of 130 studies. PLoS Med 3:e91
Yin ZH, Cui ZG, Ren YW, Su M, Ma R, He QC, Zhou BS (2013) TP63 gene polymorphisms, cooking oil fume exposure and risk of lung adenocarcinoma in chinese non-smoking females. Asian Pac J Cancer Prev 14:6519–6522
Zhang Y, Gu C, Shi H, Zhang A, Kong X, Bao W, Deng D, Ren L, Gu D (2012) Association between C3orf21, TP63 polymorphisms and environment and NSCLC in never-smoking Chinese population. Gene 497:93–97
Zhao Y, Wang S, Aunan K, Seip HM, Hao J (2006) Air pollution and lung cancer risks in China–a meta-analysis. Sci Total Environ 366:500–513
Zhou W, Heist RS, Liu G, Asomaning K, Miller DP, Neuberg DS, Wain JC, Lynch TJ, Christiani DC (2006) Second hand smoke exposure and survival in early-stage non-small-cell lung cancer patients. Clin Cancer Res 12:7187–7193
Zhou C, Chen H, Wang A (2013) P53 codon 72 polymorphism and lung cancer risk: evidence from 27,958 subjects. Tumour Biol 34:2961–2969
Conflict of interest
The authors declare that they have no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Additional information
Communicated by S. Hohmann.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Jin, Yx., Jiang, Gn., Zheng, H. et al. Common genetic variants on 3q28 contribute to non-small cell lung cancer susceptibility: evidence from 10 case-control studies. Mol Genet Genomics 290, 573–584 (2015). https://doi.org/10.1007/s00438-014-0934-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00438-014-0934-1