covid
Buscar en
GE - Portuguese Journal of Gastroenterology
Toda la web
Inicio GE - Portuguese Journal of Gastroenterology Genetic Variations and Gastric Cancer Risk
Información de la revista
Vol. 22. Núm. 4.
Páginas 135-136 (julio - agosto 2015)
Compartir
Compartir
Descargar PDF
Más opciones de artículo
Vol. 22. Núm. 4.
Páginas 135-136 (julio - agosto 2015)
Editorial
Open Access
Genetic Variations and Gastric Cancer Risk
Alterações Genéticas e Risco de Cancro Gástrico
Visitas
2388
Ricardo Marcos-Pinto
Gastroenterology Department, Centro Hospitalar do Porto, Porto, Portugal
Contenido relacionado
GE Portuguese Journal of Gastroenterology. 2015;22:143-5210.1016/j.jpge.2015.04.001
Ana Maria Sampaio, Sandra Caramujo Balseiro, Maria Reis Silva, Ana Alarcão, Maria João d’Aguiar, Teresa Ferreira, Lina Carvalho
Este artículo ha recibido

Under a Creative Commons license
Información del artículo
Texto completo
Bibliografía
Descargar PDF
Estadísticas
Texto completo

Gastric cancer used to be the leading cause of cancer deaths in the world until the 1980 when it was overtaken by lung cancer.1 Nowadays, stomach cancer is the second leading cause of cancer death in both sexes worldwide. In spite of worldwide global decrease, in 2020 (using computing models), the prevalence of gastric cancer is expected to rise in Portugal, for both sexes (Globocan). Most patients die during the first year after the diagnosis, even if submitted to costly and aggressive therapy.2

Intestinal type is more frequently observed in older patients and represents the end product of a cascade of events that begin with multifocal atrophic gastritis after exposure to environmental risk factors like Helicobacter pylori (H. pylori) infection. This is usually accompanied by intestinal metaplasia and leads to cancer via dysplasia.3 This lengthy process, commonly known as Correa Cascade, is dependent on continued chronic inflammation.4–6

Unlike intestinal gastric cancer, the diffuse type typically develops following chronic inflammation without passing through the intermediate steps of glandular atrophy and intestinal metaplasia. So far, H. pylori gastritis is the only universal precursor condition for this subtype of gastric cancer.7,8

Significant advances toward the understanding of gastric carcinogenesis have been achieved since the identification of H. pylori by Marshall and Warren in 1984,9 and its latter classification as a class I carcinogen by the International Agency for Research on Cancer. Colonization is usually asymptomatic and tumor progression only occurs in a subset of individuals and is dependent on the host response as well as genetic variation of the bacteria.10

An immensity of genes and genetic variations and its implications in gastric carcinogenesis has been addressed although its relevance is not always clear. In the last few years, the role of host genetic interleukin polymorphisms has been widely studied regarding premalignant lesions and as biomarkers for genetic susceptibility in gastric cancer development. The best characterized by population-association studies are those respecting the inflammatory response to H. pylori infection and the damage-induced inflammation of the gastric mucosa leading to mucosal atrophy and progression to gastric cancer, mainly IL-1β, IL1 Receptor Antagonist (IL-1RN), IL8IL10 and TNF-α. Genetic polymorphisms directly influence inter-individual variation in the magnitude of cytokine response and this clearly contributes to an individual's ultimate clinical outcome. Early studies by El-Omar showed an association of gastric cancer risk with the genotypes carrying IL-1β-511T, IL-1β-31T and IL-1RN*2/*2 with OR of 2.5, 2.6 and 3.7 for the homozygotes.11 Studies on Portuguese population confirmed the relevance of some of the proinflammatory polymorphisms and genetic variations of H. pylori.12–15 Following results were inconsistent because of variation of allele frequencies in different ethnic groups, tumor type and location, H. pylori infection, methodologies and quality of studies.16,17

The study of host genetics brought a better understanding of disease pathogenesis and helped in confirming two key-points: the important role of H. pylori infection in gastric carcinogenesis and the role of chronic inflammation with its long-term deleterious effects on gastric physiology. However, the heterogeneity of results at the present time makes it difficult to translate them into recommendations for daily clinical practice.

In this issue of GE, Carvalho L et al describes the association between host cytokines polymorphisms and gastric cancer risk, namely IL-4 and IL-6.18 It concludes that specific IL-4 and IL-6 polymorphisms are associated with GC risk either the Lauren's diffuse type and/or the intestinal type. Some limitations could be pointed such as the low number of patients and controls in the context of genetic association studies, the representativeness of population and the accuracy of the data. Nevertheless, new insights about the role of IL-6 and IL-4 expression variants and gastric inflammation/cancer risk in a Portuguese population are presented.

References
[1]
P. Pisani, D.M. Parkin, J. Ferlay.
Estimates of the worldwide mortality from eighteen major cancers in 1985. Implications for prevention and projections of future burden.
Int J Cancer, 55 (1993), pp. 891-903
[2]
A. Diaz De Liano, F. Oteiza Martinez, M.A. Ciga, M. Aizcorbe, F. Cobo, R. Trujillo.
Impact of surgical procedure for gastric cancer on quality of life.
Br J Surg, 90 (2003), pp. 91-94
[3]
M. Dinis-Ribeiro, M. Areia, A.C. de Vries, R. Marcos-Pinto, M. Monteiro-Soares, A. O’Connor, et al.
Management of precancerous conditions and lesions in the stomach (MAPS): guideline from the European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter Study Group (EHSG), European Society of Pathology (ESP), and the Sociedade Portuguesa de Endoscopia Digestiva (SPED).
Endoscopy, 44 (2012), pp. 74-94
[4]
P. Lauren.
The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. An attempt at a histo-clinical classification.
Acta Pathol Microbiol Scand, 64 (1965), pp. 31-49
[5]
P. Correa.
Human gastric carcinogenesis: a multistep and multifactorial process – First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention.
Cancer Res, 52 (1992), pp. 6735-6740
[6]
P. Correa, W. Haenszel, C. Cuello, S. Tannenbaum, M. Archer.
A model for gastric cancer epidemiology.
Lancet, 2 (1975), pp. 58-60
[7]
C. Weydig, A. Starzinski-Powitz, G. Carra, J. Lower, S. Wessler.
CagA-independent disruption of adherence junction complexes involves E-cadherin shedding and implies multiple steps in Helicobacter pylori pathogenicity.
Exp Cell Res, 313 (2007), pp. 3459-3471
[8]
S.S. Pinho, S. Carvalho, R. Marcos-Pinto, A. Magalhaes, C. Oliveira, J. Gu, et al.
Gastric cancer: adding glycosylation to the equation.
Trends Mol Med, 19 (2013), pp. 664-676
[9]
B.J. Marshall, J.R. Warren.
Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration.
Lancet, 1 (1984), pp. 1311-1315
[10]
J.C. Atherton.
The pathogenesis of Helicobacter pylori-induced gastro-duodenal diseases.
[11]
E.M. El-Omar, K. Oien, L.S. Murray, A. El-Nujumi, A. Wirz, D. Gillen, et al.
Increased prevalence of precancerous changes in relatives of gastric cancer patients: critical role of H. pylori.
Gastroenterology, 118 (2000), pp. 22-30
[12]
C. Figueiredo, J.C. Machado, P. Pharoah, R. Seruca, S. Sousa, R. Carvalho, et al.
Helicobacter pylori and interleukin 1 genotyping: an opportunity to identify high-risk individuals for gastric carcinoma.
J Natl Cancer Inst, 94 (2002), pp. 1680-1687
[13]
J.C. Machado, C. Figueiredo, P. Canedo, P. Pharoah, R. Carvalho, S. Nabais, et al.
A proinflammatory genetic profile increases the risk for chronic atrophic gastritis and gastric carcinoma.
Gastroenterology, 125 (2003), pp. 364-371
[14]
R. Marcos-Pinto, F. Carneiro, M. Dinis-Ribeiro, X. Wen, C. Lopes, C. Figueiredo, et al.
First-degree relatives of patients with early-onset gastric carcinoma show even at young ages a high prevalence of advanced OLGA/OLGIM stages and dysplasia.
Aliment Pharmacol Ther, 35 (2012), pp. 1451-1459
[15]
R. Marcos-Pinto, M. Dinis-Ribeiro, F. Carneiro, X. Wen, C. Lopes, C. Figueiredo, et al.
First-degree relatives of early-onset gastric cancer patients show a high risk for gastric cancer: phenotype and genotype profile.
Virchows Arch, 463 (2013), pp. 391-399
[16]
M. Yin, Z. Hu, D. Tan, J.A. Ajani, Q. Wei.
Molecular epidemiology of genetic susceptibility to gastric cancer: focus on single nucleotide polymorphisms in gastric carcinogenesis.
Am J Transl Res, 1 (2009), pp. 44-54
[17]
C. Persson, P. Canedo, J.C. Machado, E.M. El-Omar, D. Forman.
Polymorphisms in inflammatory response genes and their association with gastric cancer: a HuGe systematic review and meta-analyses.
Am J Epidemiol, 173 (2011), pp. 259-270
[18]
A.M. Sampaio, S.C. Balseiro, M.R. Silva, A. Alarcão, M.J. d’Aguiar, T. Ferreira, et al.
Association between IL-4 and IL-6 expression variants and gastric cancer among portuguese population.
GE Port J Gastroenterol, 22 (2015), pp. 143-152
Copyright © 2015. Sociedade Portuguesa de Gastrenterologia
Descargar PDF
Opciones de artículo
es en pt

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos