Grant Number:	5R01CA098309-03 Interpret this number
Primary Investigator:	Kato, Ikuko
Organization:	Wayne State University
Project Title:	Genetic Susceptibility to Infection Related Cancer
Fiscal Year:	2005

DESCRIPTION (provided by applicant): The long-term goal of the proposed study is to provide a scientific basis to develop efficient primary prevention strategies against infection/inflammation-related cancers. Mounting evidence suggests that a variety of infectious agents have a role in the pathogenesis of human cancers. It is estimated that 15.6 percent of the worldwide cancer incidences in 1990 can be attributed to these infectious agents, accounting for a total of 1,450,000 cases. Helicobacter pylori (HP) is ranked top among various infectious agents and represents approximately 5 percent of new cancer cases in the world. These cancers are important from a public health point of view because they are potentially preventable by antibiotics treatment or vaccination. Whereas HP infection is very common (80-90 percent) in populations with high risk for stomach cancer, it is known that only a very small fraction of the population infected with HP actually develops cancer, suggesting a role for genetic components in HP-related carcinogenesis in addition to that of environmental co-factors. This proposal will specifically focus on the 2 groups of polymorphic genes, receptors to HP lipopolysaccharide (LPS), a cell wall component, which elicits immediate proinflammatory responses, (1) CD14 (C-260T), (2) TRL4 (A896G) and (3) NOD2 (3020insC); and resultant cytokines, (4) IL-8 (T-251A), (5) MCP1 (G-2518A), (6) IL-lbeta (T-31C) and (7) TNF-alpha (G-308A). These polymorphic genes are known to be functional and have been postulated to modify host responses to HP infection. The proposed study will be designed as a spin-off study of a chemo prevention trial for gastric cancer in Venezuela, taking advantage of unique characteristics of the study population, i.e., a strikingly high (95 percent) HP infection rate and high prevalence of gastric premalignant lesions. It will utilize biological specimens and epidemiological and histopathological data collected at the baseline examination from the 2200 participants. Genomic DNA will be isolated from these specimens and tested for the polymorphic genes listed above. The specific aim of the proposed study is to evaluate whether those genotypes or alleles of the polymorphic genes which lead to greater responses to HP infection are associated with increased risk of high-grade gastric precancerous lesions. Secondary aims include to examine histopathological correlates of these polymorphisms and to determine whether selected environmental factors modify the above associations.




TAS2R38 polymorphisms, Helicobacter pylori infection and susceptibility to gastric cancer and premalignant gastric lesions.
Authors: Giaccherini M. , Rizzato C. , Gentiluomo M. , Lupetti A. , Flores-Luna L. , Vivas J. , Bravo M.M. , Kasamatsu E. , Muñoz N. , Canzian F. , et al. .
Source: European Journal Of Cancer Prevention : The Official Journal Of The European Cancer Prevention Organisation (ecp), 2021-10-11 00:00:00.0; , .
EPub date: 2021-10-11 00:00:00.0.
PMID: 34653070
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Risk Of Advanced Gastric Precancerous Lesions In Helicobacter Pylori Infected Subjects Is Influenced By Abo Blood Group And Caga Status
Authors: Rizzato C. , Kato I. , Plummer M. , Muñoz N. , Stein A. , Jan van Doorn L. , Franceschi S. , Canzian F. .
Source: International Journal Of Cancer, 2013-07-15 00:00:00.0; 133(2), p. 315-22.
PMID: 23319424
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Genetic Variation In Psca And Risk Of Gastric Advanced Preneoplastic Lesions And Cancer In Relation To Helicobacter Pylori Infection
Authors: Rizzato C. , Kato I. , Plummer M. , Muñoz N. , Canzian F. .
Source: Plos One, 2013; 8(9), p. e73100.
PMID: 24023815
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Genetic Polymorphisms In Mediators Of Inflammation And Gastric Precancerous Lesions
Authors: Canzian F. , Franceschi S. , Plummer M. , van Doorn L.J. , Lu Y. , Gioia-Patricola L. , Vivas J. , Lopez G. , Severson R.K. , Schwartz A.G. , et al. .
Source: European Journal Of Cancer Prevention : The Official Journal Of The European Cancer Prevention Organisation (ecp), 2008 Apr; 17(2), p. 178-83.
PMID: 18287876
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Helicobacter Pylori Cytotoxin-associated Genotype And Gastric Precancerous Lesions
Authors: Plummer M. , van Doorn L.J. , Franceschi S. , Kleter B. , Canzian F. , Vivas J. , Lopez G. , Colin D. , Muñoz N. , Kato I. .
Source: Journal Of The National Cancer Institute, 2007-09-05 00:00:00.0; 99(17), p. 1328-34.
PMID: 17728213
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Polymorphisms In Genes Related To Bacterial Lipopolysaccharide/peptidoglycan Signaling And Gastric Precancerous Lesions In A Population At High Risk For Gastric Cancer
Authors: Kato I. , Canzian F. , Plummer M. , Franceschi S. , van Doorn L.J. , Vivas J. , Lopez G. , Lu Y. , Gioia-Patricola L. , Severson R.K. , et al. .
Source: Digestive Diseases And Sciences, 2007 Jan; 52(1), p. 254-61.
PMID: 17171451
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Genetic Polymorphisms In Anti-inflammatory Cytokine Signaling And The Prevalence Of Gastric Precancerous Lesions In Venezuela
Authors: Kato I. , Canzian F. , Franceschi S. , Plummer M. , van Doorn L.J. , Lu Y. , Gioia-Patricola L. , Vivas J. , Lopez G. , Severson R.K. , et al. .
Source: Cancer Causes & Control : Ccc, 2006 Nov; 17(9), p. 1183-91.
PMID: 17006724
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Host-bacterial Interaction In The Development Of Gastric Precancerous Lesions In A High Risk Population For Gastric Cancer In Venezuela
Authors: Kato I. , van Doorn L.J. , Canzian F. , Plummer M. , Franceschi S. , Vivas J. , Lopez G. , Lu Y. , Gioia-Patricola L. , Severson R.K. , et al. .
Source: International Journal Of Cancer, 2006-10-01 00:00:00.0; 119(7), p. 1666-71.
PMID: 16671087
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Use Of Whole Genome Amplification To Rescue Dna From Plasma Samples
Authors: Lu Y. , Gioia-Patricola L. , Gomez J.V. , Plummer M. , Franceschi S. , Kato I. , Canzian F. .
Source: Biotechniques, 2005 Oct; 39(4), p. 511-5.
PMID: 16235563
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Environmental Factors In Helicobacter Pylori-related Gastric Precancerous Lesions In Venezuela
Authors: Kato I. , Vivas J. , Plummer M. , Lopez G. , Peraza S. , Castro D. , Sanchez V. , Cano E. , Andrade O. , Garcia R. , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2004 Mar; 13(3), p. 468-76.
PMID: 15006925
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