Loci identified through genome-wide association studies and lung cancer risk: is there anything more?

Loci identificados através de estudo de associação genômica ampla e risco de câncer do pulmão: existe algo mais?

Ramon Andrade De Mello António Araújo Venceslau Hespanhol Rui Manuel Reis About the authors

Dear Editor,

Recently, lung cancer screening has acquired a position of central interest among the scientific community. Many risk factors for non-small-cell lung cancer (NSCLC) susceptibility have already been identified, such as tobacco exposure, occupational exposure, random exposure, silicosis and passive smoking.11. Dias OM, Turato ER. Cigarette smokers views on their habit and the causes of their illness following lung cancer diagnosis: a clinical-qualitative study. Sao Paulo Med J. 2006;124(3):125-9.,22. de Mello RA, Costa BM, Reis RM, Hespanhol V. Insights into angiogenesis in non-small cell lung cancer: molecular mechanisms, polymorphic genes, and targeted therapies. Recent Pat Anticancer Drug Discov. 2012;7(1):118-31. This knowledge has raised certain questions: Is there any clinical tool suitable for screening for NSCLC with good cost-effectiveness? Is there any therapeutic choice that could improve NSCLC case prognoses through an early approach? Is there any specific population that benefit from NSCLC screening and strategies for implementing an early approach?

In 2009, a genome-wide association study (GWAS) was conducted on more than 5,000 lung cancer cases.33. Landi MT, Chatterjee N, Yu K, 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(5):679-91. It was reported that some genetic polymorphisms located on chromosomes 5p15.33 and 15q25.1 were associated with a risk of adenocarcinoma in a Western population.33. Landi MT, Chatterjee N, Yu K, 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(5):679-91. In May 2012, Ito et al.44. Ito H, McKay JD, Hosono S, et al. Association between a genome-wide association study-identified locus and the risk of lung cancer in Japanese population. J Thorac Oncol. 2012;7(5):790-8. assessed the genotyping in 716 Japanese lung cancer cases and 716 matched controls. This Japanese study showed that the variants rs12914385 and rs931794 on 15q25 modified the effect of cumulative tobacco smoking on lung cancer risk, but that these two loci showed no statistically significant main effects on lung cancer risk. Furthermore, they reported that the associations shown by the TERT-CLPM1L locus on 5p15 with lung cancer risk among Japanese patients were of a similar magnitude to those among Western patients.44. Ito H, McKay JD, Hosono S, et al. Association between a genome-wide association study-identified locus and the risk of lung cancer in Japanese population. J Thorac Oncol. 2012;7(5):790-8. Meanwhile, a Portuguese study55. de Mello RA, Ferreira M, Costa S, et al. Association between EGF +61 genetic polymorphisms and non-small cell lung cancer increased risk in a Portuguese population: a case-control study. Tumour Biol. 2012;33(5):1341-8. reported that epidermal growth factor (EGF)+61 genetic A/G polymorphisms were also associated with increased risk of NSCLC in a Portuguese population. EGF +61 A/G genetic polymorphisms are located on chromosome 4 and have also previously been reported to be risk factors for glioma and predictive biomarkers for cetuximab in colorectal cancer cases.55. de Mello RA, Ferreira M, Costa S, et al. Association between EGF +61 genetic polymorphisms and non-small cell lung cancer increased risk in a Portuguese population: a case-control study. Tumour Biol. 2012;33(5):1341-8.

In this manner, the genome has now acquired a central role in NSCLC susceptibility.33. Landi MT, Chatterjee N, Yu K, 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(5):679-91.66. Wünsch-Filho V, Boffetta P, Colin D, Moncau JE. Familial cancer aggregation and the risk of lung cancer. Sao Paulo Med J. 2002;120(2):38-44. Recent studies have shown that low-dose computed tomography could serve as an important screening tool in selected populations.55. de Mello RA, Ferreira M, Costa S, et al. Association between EGF +61 genetic polymorphisms and non-small cell lung cancer increased risk in a Portuguese population: a case-control study. Tumour Biol. 2012;33(5):1341-8. Currently, many therapeutic options are possible for NSCLC treatment: surgery for the early stages, and also target therapies for advanced cases with good performance status.22. de Mello RA, Costa BM, Reis RM, Hespanhol V. Insights into angiogenesis in non-small cell lung cancer: molecular mechanisms, polymorphic genes, and targeted therapies. Recent Pat Anticancer Drug Discov. 2012;7(1):118-31.,77. Saad IA, Botega NJ, Toro IF. Predictors of quality-of-life improvement following pulmonary resection due to lung cancer. Sao Paulo Med J. 2007;125(1):46-9. We believe that taking genome studies into consideration in identifying populations at risk could improve NSCLC screening strategies and therefore would help oncologists to implement prompt approaches.

REFERENCES

  • 1
    Dias OM, Turato ER. Cigarette smokers views on their habit and the causes of their illness following lung cancer diagnosis: a clinical-qualitative study. Sao Paulo Med J. 2006;124(3):125-9.
  • 2
    de Mello RA, Costa BM, Reis RM, Hespanhol V. Insights into angiogenesis in non-small cell lung cancer: molecular mechanisms, polymorphic genes, and targeted therapies. Recent Pat Anticancer Drug Discov. 2012;7(1):118-31.
  • 3
    Landi MT, Chatterjee N, Yu K, 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(5):679-91.
  • 4
    Ito H, McKay JD, Hosono S, et al. Association between a genome-wide association study-identified locus and the risk of lung cancer in Japanese population. J Thorac Oncol. 2012;7(5):790-8.
  • 5
    de Mello RA, Ferreira M, Costa S, et al. Association between EGF +61 genetic polymorphisms and non-small cell lung cancer increased risk in a Portuguese population: a case-control study. Tumour Biol. 2012;33(5):1341-8.
  • 6
    Wünsch-Filho V, Boffetta P, Colin D, Moncau JE. Familial cancer aggregation and the risk of lung cancer. Sao Paulo Med J. 2002;120(2):38-44.
  • 7
    Saad IA, Botega NJ, Toro IF. Predictors of quality-of-life improvement following pulmonary resection due to lung cancer. Sao Paulo Med J. 2007;125(1):46-9.

Publication Dates

  • Publication in this collection
    Apr 2013

History

  • Reviewed
    3 May 2012
  • Received
    25 Sept 2012
  • Accepted
    25 Sept 2012
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