Skip to main content
SpringerLink
Log in

EGF+61 A>G polymorphism is not associated with lung cancer risk in the Brazilian population

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Epidermal growth factor (EGF) and its receptor (EGFR) play an important role in lung carcinogenesis. A functional single nucleotide polymorphism (SNP) in EGF promoter region (EGF+61 A>G—rs4444903) has been associated with cancer susceptibility. Yet, in lung cancer, the EGF+61 A>G role is unclear. The aim of this study was to evaluate the risk of lung cancer associated with EGF+61 A>G SNP in the Brazilian population. For that, 669 lung cancer patients and 1104 controls were analyzed. EGF+61 A>G genotype was assessed by PCR-RFLP and TaqMan genotyping assay. Both patients and controls were in Hardy–Weinberg equilibrium. As expected, uni- and multivariate analyses showed that tobacco consumption and age were significant risk factors for lung cancer. The genotype frequencies in lung cancer patients were 27.3% of AA, 47.4% of AG and 25.3% of GG, and for controls were 25.3% of AA, 51.6% of AG and 23.1% of GG. The allele frequencies were 51.1% of A and 48.9% of G for both cases and controls. No significant differences for the three genotypes (AA, AG and GG—codominant model) were observed between cases and controls. We then grouped AG and GG (recessive model) genotypes, as well as AA and AG (dominant model), and again, no significant differences were also found. This is the largest study to explore EGF+61 A>G polymorphism association with lung cancer risk and suggests that this SNP is not a risk factor for lung cancer in the Brazilian population.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Data Availability

All data generated or analyzed during this study are included in this published article (and its supplementary information files).

References

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. https://doi.org/10.3322/caac.21492

    Article  PubMed  Google Scholar 

  2. INCA (2018) Estimativas 2018. In. INCA. http://www.inca.gov.br/estimativa/2018/. Accessed 04 Oct 2018

  3. DATASUS (2018) Sistema de informações sobre mortalidade. In: Ministério da Saúde. http://www.datasus.gov.br. Accessed 14 Jan 2019

  4. Akhtar N, Bansal JG (2017) Risk factors of Lung Cancer in nonsmoker. Curr Probl Cancer. https://doi.org/10.1016/j.currproblcancer.2017.07.002

    Article  PubMed  Google Scholar 

  5. Wee P, Wang Z (2017) Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways. Cancers (Basel). https://doi.org/10.3390/cancers9050052

    Article  Google Scholar 

  6. Dibble CC, Cantley LC (2015) Regulation of mTORC1 by PI3K signaling. Trends Cell Biol 25(9):545–555. https://doi.org/10.1016/j.tcb.2015.06.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Normanno N, Bianco C, De Luca A, Salomon DS (2001) The role of EGF-related peptides in tumor growth. Front Biosci J Virtual Libr 6:D685–D707

    Article  CAS  Google Scholar 

  8. TCGA The Cancer Genome Atlas. https://tcga-data.nci.nih.gov/docs/publications/tcga/?. Accessed 28 Sept 2018

  9. ICGC International Cancer Genome Consortium. https://dcc.icgc.org/

  10. Jordan EJ, Kim HR, Arcila ME, Barron D, Chakravarty D, Gao J, Chang MT, Ni A, Kundra R, Jonsson P, Jayakumaran G, Gao SP, Johnsen HC, Hanrahan AJ, Zehir A, Rekhtman N, Ginsberg MS, Li BT, Yu HA, Paik PK, Drilon A, Hellmann MD, Reales DN, Benayed R, Rusch VW, Kris MG, Chaft JE, Baselga J, Taylor BS, Schultz N, Rudin CM, Hyman DM, Berger MF, Solit DB, Ladanyi M, Riely GJ (2017) Prospective comprehensive molecular characterization of lung adenocarcinomas for efficient patient matching to approved and emerging therapies. Cancer Discov 7(6):596–609. https://doi.org/10.1158/2159-8290.CD-16-1337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Jurisic V, Obradovic J, Pavlovic S, Djordjevic N (2018) Epidermal Growth Factor Receptor Gene in Non-Small-Cell Lung Cancer: The Importance of Promoter Polymorphism Investigation. Anal Cell Pathol 2018:6192187. https://doi.org/10.1155/2018/6192187

    Article  CAS  Google Scholar 

  12. Shahbazi M, Pravica V, Nasreen N, Fakhoury H, Fryer AA, Strange RC, Hutchinson PE, Osborne JE, Lear JT, Smith AG, Hutchinson IV (2002) Association between functional polymorphism in EGF gene and malignant melanoma. Lancet 359(9304):397–401. https://doi.org/10.1016/S0140-6736(02)07600-6

    Article  CAS  PubMed  Google Scholar 

  13. Costa BM, Ferreira P, Costa S, Canedo P, Oliveira P, Silva A, Pardal F, Suriano G, Machado JC, Lopes JM, Reis RM (2007) Association between functional EGF + 61 polymorphism and glioma risk. Clin Cancer Res Off J Am Assoc Cancer Res 13(9):2621–2626. https://doi.org/10.1158/1078-0432.CCR-06-2606

    Article  CAS  Google Scholar 

  14. Wu SJ, Jiang SY, Wu J, Xiong GL (2015) Association between EGF+61 A>G polymorphism and gastric cancer risk: A meta-analysis. J Huazhong Univ Sci Technol Med Sci 35(3):327–332. https://doi.org/10.1007/s11596-015-1432-3

    Article  CAS  PubMed  Google Scholar 

  15. Sun S, Jin GJ, Zhao Y, Kang H (2015) Association between the epidermal growth factor 61*A/G polymorphism and hepatocellular carcinoma risk: a meta-analysis. Asian Pac J Cancer Prev APJCP 16(7):3009–3014

    Article  PubMed  Google Scholar 

  16. Chen X, Yang G, Zhang D, Zhang W, Zou H, Zhao H, Zhang X, Zhao S (2014) Association between the epidermal growth factor + 61 G/A polymorphism and glioma risk: a meta-analysis. PLoS ONE 9(4):e95139. https://doi.org/10.1371/journal.pone.0095139

    Article  PubMed  PubMed Central  Google Scholar 

  17. Lim YJ, Kim JW, Song JY, Hong MS, Jin SY, Yoon SH, Park HJ, Choe BK, Lee JJ, Yim SV, Hong SI, Baik HH, Ha E, Park YH (2005) Epidermal growth factor gene polymorphism is different between schizophrenia and lung cancer patients in Korean population. Neurosci Lett 374(3):157–160. https://doi.org/10.1016/j.neulet.2004.10.055

    Article  CAS  PubMed  Google Scholar 

  18. Kang HG, Choi JE, Lee WK, Kam S, Cha SI, Kim CH, Jung TH, Park JY (2007) +61 A>G polymorphism in the EGF gene does not increase the risk of lung cancer. Respirology 12:902–905. https://doi.org/10.1111/j.1440-1843.2007.01152.x

    Article  PubMed  Google Scholar 

  19. de Mello RA, Ferreira M, Costa S, Costa BM, Pires FS, Neves I, Almeida MI, Cunha J, Oliveira P, Hespanhol V, Reis RM (2012) Association between EGF + 61 genetic polymorphisms and non-small cell lung cancer increased risk in a Portuguese population: a case-control study. Tumour Biol 33(5):1341–1348. https://doi.org/10.1007/s13277-012-0382-7

    Article  CAS  PubMed  Google Scholar 

  20. Masroor M, Amit J, Javid J, Mir R, Prasant Y, Imtiyaz A, Mariyam Z, Mohan A, Ray PC, Saxena A (2015) Clinical implication of EGF A61G polymorphism in the risk of non small cell lung adenocarcinoma patients: a case control study. Asian Pac J Cancer Prev 16(17):7529–7534

    Article  PubMed  Google Scholar 

  21. Genomes Project C, Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, Korbel JO, Marchini JL, McCarthy S, McVean GA, Abecasis GR (2015) A global reference for human genetic variation. Nature 526(7571):68–74. https://doi.org/10.1038/nature15393

    Article  CAS  Google Scholar 

  22. Cui L, Pan XM, Ma CF, Shang-Guan J, Yu HB, Chen GX, Wang J (2010) Association between epidermal growth factor polymorphism and esophageal squamous cell carcinoma susceptibility. Dig Dis Sci 55(1):40–45. https://doi.org/10.1007/s10620-008-0700-5

    Article  CAS  PubMed  Google Scholar 

  23. Teixeira AL, Ribeiro R, Cardoso D, Pinto D, Lobo F, Fraga A, Pina F, Calais-da-Silva F, Medeiros R (2008) Genetic polymorphism in EGF is associated with prostate cancer aggressiveness and progression-free interval in androgen blockade-treated patients. Clin Cancer Res 14(11):3367–3371. https://doi.org/10.1158/1078-0432.CCR-07-5119

    Article  CAS  PubMed  Google Scholar 

  24. Wu GY, Hasenberg T, Magdeburg R, Bonninghoff R, Sturm JW, Keese M (2009) Association between EGF, TGF-beta1, VEGF gene polymorphism and colorectal cancer. World J Surg 33(1):124–129. https://doi.org/10.1007/s00268-008-9784-5

    Article  PubMed  Google Scholar 

  25. Li TF, Ren KW, Liu PF (2012) Meta-analysis of epidermal growth factor polymorphisms and cancer risk: involving 9779 cases and 15,932 controls. DNA Cell Biol 31(4):568–574. https://doi.org/10.1089/dna.2011.1394

    Article  CAS  PubMed  Google Scholar 

  26. Callegari-Jacques SM, Grattapaglia D, Salzano FM, Salamoni SP, Crossetti SG, Ferreira ME, Hutz MH (2003) Historical genetics: spatiotemporal analysis of the formation of the Brazilian population. Am J Hum Biol 15(6):824–834. https://doi.org/10.1002/ajhb.10217

    Article  PubMed  Google Scholar 

  27. Zhang YM, Cao C, Liang K (2010) Genetic polymorphism of epidermal growth factor 61A>G and cancer risk: a meta-analysis. Cancer Epidemiol 34(2):150–156. https://doi.org/10.1016/j.canep.2010.02.004

    Article  CAS  PubMed  Google Scholar 

  28. Rose S, Laan MJ (2009) Why match? Investigating matched case-control study designs with causal effect estimation. Int J Biostat 5(1):Article 1. https://doi.org/10.2202/1557-4679.1127

    Article  PubMed  Google Scholar 

  29. Elez-Burnjakovic N, Ugrin M, Obradovic J, Miletic N, Racic M, Kulic M, Pavlovic S, Jurisic V (2018) Distribution of EGFR SNPs - 191C/A and 181946G/A in patients with lung cancer depending on smoking status in the Republic of Srpska, Bosnia and Herzegovina. J BUON Off J Balk Union Oncol 23(2):384–390

    Google Scholar 

  30. Bashir NA, Ragab ES, Khabour OF, Khassawneh BY, Alfaqih MA, Momani JA (2018) The Association between Epidermal Growth Factor Receptor (EGFR) Gene Polymorphisms and Lung Cancer Risk. Biomolecules. https://doi.org/10.3390/biom8030053

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Barretos Cancer Hospital Research Support Department (NAP) for sample collection and Barretos Cancer Hospital Biobank for sample processing.

Funding

This study was partially supported by FINEP - CT-INFRA (02/2010) and Barretos Cancer Hospital Research Fund (PAIP).

Author information

Authors and Affiliations

  1. Molecular Oncology Research Center, Barretos Cancer Hospital, Antenor Duarte Villela St, 1331, Barretos, SP, 14784-400, Brazil

    Ana Carolina Laus, Flavia Escremim de Paula, Carolina Dias Carlos, Izabela Natalia Faria Gomes & Rui Manuel Reis

  2. Epidemiology and Biostatistics Department, Barretos Cancer Hospital, Barretos, Brazil

    Marcos Alves de Lima

  3. Medical Oncology Department, Barretos Cancer Hospital, Barretos, Brazil

    Pedro de Marchi, Jenna Kadja Neves Valente, Ana Beatriz Maringolo Pioltini & Luciano de Souza Viana

  4. Surgery Department, Barretos Cancer Hospital, Barretos, Brazil

    José Elias Miziara & Carlos Maciel da Silva

  5. Pathology Department, Barretos Cancer Hospital, Barretos, Brazil

    Cristovam Scapulatempo-Neto

  6. Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal

    Rui Manuel Reis

  7. ICVS/3B’s – PT Government Associate Laboratory, Braga/Guimarães, Portugal

    Rui Manuel Reis

Authors
  1. Ana Carolina Laus
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Flavia Escremim de Paula
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marcos Alves de Lima
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Carolina Dias Carlos
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Izabela Natalia Faria Gomes
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Pedro de Marchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jenna Kadja Neves Valente
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ana Beatriz Maringolo Pioltini
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. José Elias Miziara
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Carlos Maciel da Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Luciano de Souza Viana
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Cristovam Scapulatempo-Neto
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Rui Manuel Reis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rui Manuel Reis.

Ethics declarations

Conflict of interest

None of the authors have any financial or non-financial conflict of interests.

Ethical approval

All procedures performed in this study were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration or its later amendments or comparable ethical standards. The study was approved by Barretos Cancer Hospital Ethics Committee (#596/2012).

Informed consent

Signed informed consents were obtained from all control individuals and cases included in the study that provided blood samples. From the FFPE cases, due to the retrospective nature of the study, the Barretos Cancer Hospital Ethics Committee exempted informed consent.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 13 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Laus, A.C., de Paula, F.E., de Lima, M.A. et al. EGF+61 A>G polymorphism is not associated with lung cancer risk in the Brazilian population. Mol Biol Rep 46, 2417–2425 (2019). https://doi.org/10.1007/s11033-019-04702-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-019-04702-0

Keywords

Search

Navigation