Abstract
Several studies including genomewide association studies (GWASs) in diverse ethnic populations have reported a significant association of genetic variant rs10937405 of TP63 with nonsmall cell lung cancer (NSCLC). However, no data are available from any Indian population on the association of this variant with NSCLC. Using TaqMan genotyping chemistry, we conducted a case–control study involving 190 NSCLC cases and 400 ethnic, age-matched controls to explore the association of rs10937405 genetic variant with NSCLC in patients from north India. Our data support that the rs10937405 variant is also significantly associated with the NSCLC and is a risk factor in the north Indian populations to develop NSCLC. However, unlike most other studies, the wild-type allele T appears to be the risk allele, as its frequency was significantly higher in the cases than controls (0.439 in cases versus 0.383 in controls. OR = 1.95 (1.23–3.09 at 95% CI); P value (adjusted) = 0.004). Genetic association was also observed by applying different genetic models. The present study provides important information of the genetic aetiology of NSCLC and strengthens GWAS findings, highlighting the role of TP63 in lung cancer risk.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Amos C. I., Wu X., Broderick P., Gorlov I. P., Gu J., Eisen T. et al. 2008 Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1. Nat. Genet. 40, 616.
Dhar G. M., Shah G. N., Naheed and Hafiza B. 1993 Epidemiological trend in the distribution of cancer in Kashmir Valley. J. Epidemiol. Community Health 47, 290–292.
Ganesh B., Sushama S., Monika S. and Suvarna P. 2011 A case-control study of risk factors for lung cancer in Mumbai, India. Asian Pac. J. Cancer Prev. 12, 357–362.
GeneCards 2018 GeneCards The Human Gene Database 2018, vol. v4.7.1 Build 10. Weizmann Institute of Science, Isreal.
Hosgood H. D., Wang W.-C., Hong Y.-C., Wang J.-C., Chen K., Chang I.-S. et al. 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 Q.-Y., Jin T.-B., Wang L., Zhang L., Geng T., Liang G. et al. 2014 Genetic variation in the TP63 gene is associated with lung cancer risk in the Han population. Tumor Biol. 35, 1863–1866.
Hu Z., Wu C., Shi Y., Guo H., Zhao X., Yin Z. et al. 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.
Huang Y., Jeong J. S., Okamura J., Sook-Kim M., Zhu H., Guerrero-Preston R. et al. 2012 Global tumor protein p53/p63 interactome: making a case for cisplatinchemoresistance. Cell Cycle 11, 2367–2379.
Jemal A., Bray F., Center M. M., Ferlay J., Ward E. and Forman D. 2011 Global cancer statistics. CA-Cancer J. Clin. 61, 69–90.
Malik P. S. and Raina V. 2015 Lung cancer: prevalent trends & emerging concepts. Indian J. Med. Res. 141, 5.
McKay J. D., Hung R. J., Gaborieau V., Boffetta P., Chabrier A., Byrnes G. et al. 2008 Lung cancer susceptibility locus at 5p15.33. Nat. Genet. 40, 1404.
Miki D., Kubo M., Takahashi A., Yoon K.-A., Kim J., Lee G. K. et al. 2010 Variation in TP63 is associated with lung adenocarcinoma susceptibility in Japanese and Korean populations. Nat. Genet. 42, 893.
Moll U. M. and Slade N. 2004 P63 and p73: roles in development and tumor formation. Mol. Cancer Res. 2, 371–386.
Shiraishi K., Kunitoh H., Daigo Y., Takahashi A., Goto K., Sakamoto H. et al. 2012 A genome-wide association study identifies two new susceptibility loci for lung adenocarcinoma in the Japanese population. Nat. Genet. 44, 900.
Torre L. A., Bray F., Siegel R. L., Ferlay J., Lortet-Tieulent J. and Jemal A. 2015 Global cancer statistics, 2012. CA-Cancer J. Clin. 65, 87–108.
Wang Y., Broderick P., Webb E., Wu X., Vijayakrishnan J., Matakidou A. et al. 2008 Common 5p15.33 and 6p21.33 variants influence lung cancer risk. Nat. Genet. 40, 1407.
Wang Y., Broderick P., Matakidou A., Vijayakrishnan J., Eisen T. and Houlston R. S. 2011 Variation in TP63 is associated with lung adenocarcinoma in the UK population. Cancer Epidemiol. Biomarkers Prev. 20, 1453–1462
Yin Z.-H., Cui Z.-G., Ren Y.-W., Su M., Ma R., He Q.-C. et al. 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.
Acknowledgements
RK and GRB acknowledge Department of Science & Technology, Government of India project (DST/SSTP/J&K/459) for financial assistance.
Author information
Authors and Affiliations
Corresponding author
Additional information
Corresponding Editor: S. Ganesh
Rights and permissions
About this article
Cite this article
Bhat, G.R., Bhat, A., Verma, S. et al. Genetic variant rs10937405 of TP63 and susceptibility to lung cancer risk in north Indian population. J Genet 98, 59 (2019). https://doi.org/10.1007/s12041-019-1102-5
Received:
Revised:
Accepted:
Published:
DOI: https://doi.org/10.1007/s12041-019-1102-5