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Faculdade de Medicina da Universidade do Porto. Introdução à Medicina. Genetic polymorphisms of Cox enzyme and risk of colon adenoma and adenocarcinoma: A systematic review. - PowerPoint PPT Presentation
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Genetic polymorphisms of Cox enzyme and risk of colon adenoma
and adenocarcinoma:
A systematic review
Introdução à Medicina
Faculdade de Medicina da Universidade do Porto
Ana Filipa Lima; Ana Teresa Pinheiro; Hugo André Macedo; Filipa Bazenga Fernandes; João Artur Coimbra; Lúcia Elisa Guedes; Mara Vanessa Fernandes; Miguel Pinto Freitas; Patrícia Manuela Marques; Rui Fernando Castro; Sara Sofia Gouveia; Telma Anita Brito; Mário Dinis Ribeiro.
Prof. Doutor Altamiro Costa Pereira
Introduction
Aim
Methods
Summary
► Plan of study
► Data Base selection
► Query selection
► Inclusion and exclusion criteria
► Selection of abstracts
► Selection of articles
► Extraction of data
► Statistical analyses Results
Conclusion
• Cancer is the second leading cause of death.(Robbins Basic Pathology, 2003)
• Colon cancer is the second cause of death related with cancer in Portugal.
(IARC, 2002)
Introduction
Cancer rate distribution in Portugal
• Adenomas are neoplastic polyps that range from small tumors to large lesions.
(Robbins Basic Pathology,2003)
Introduction
(Robbins Basic Pathology,2003)
(IARC, Portuguese population (Vila Nova de Gaia),1995)
Introduction
• Spontaneous mutations
• Epidemiologic factors
Cancer rate and aging
• There is strong evidence that connects a chronic
inflammatory reaction with the development of neoplasias.
Reactive Intermediates of oxygen and nitrogen
released
DNA damage
Polimorfisms in genes…IL-
1β, IL-6, TNF-α, CXCL,
CCR, COX-2COX-2
(Immunology ,2003)
Prostaglandins
Introduction
• Genetic polymorphisms are related to changes in one nucleotide or a sequence of nucleotides in DNA.
(Robbins Basic Pathology, 2003))
Introduction
• Cox enzymes (cyclooxygenase enzyme), also known as PTGS enzymes, convert arachidonic acid to prostaglandin H2, a precursor to all prostanoids, and are produced in the organism in response to inflammation in precancerous and cancerous tissues .
( Vane, J. R.,1971 )
(Biology queensu)
• To estimate the risk of colon adenoma or adenocarcinoma among individuals with Cox polymorphisms.
Aims
Cohort StudiesCase-control Studies
Observational studies
Systematic review
Methods: Type of study
• Database search using Medline PubMed:
Methods: Selection of Papers
((risk*[Title/Abstract] OR risk*[MeSH:noexp] OR risk *[MeSH:noexp] OR "case-control studies"[MeSH Terms] OR case-control studies[Text Word] OR cohort studies[MeSH Terms] OR group*[Text Word]) OR (incidence[MeSH:noexp] OR mortality[MeSH Terms] OR follow up studies[MeSH:noexp] OR prognos*[Text Word] OR predict*[Text Word] OR course*[Text Word]) )
AND
("Cyclooxygenase 2"[MeSH] OR "Cyclooxygenase 1"[MeSH] OR cox)
AND
( polymorphisms OR ("Polymorphism, Single Nucleotide"[MeSH] OR "Polymorphism, Genetic"[MeSH]))
AND
(intestine OR colon OR rectum OR colorectal)
AND
(cancer OR carcinoma OR carcinoma[Text Word] OR adenocarcinoma OR polyps OR adenoma)
48
• Database search using Scopus:
TITLE-ABS-KEY(((cancer OR carcinoma OR adenocarcinoma OR adenoma OR polyps) AND
(cox OR cyclooxygenase 2 OR "cox 2" OR cox-1 OR "cyclooxygenase 2" OR cyclooxygenase 1 OR "cyclooxygenase 1" OR ptgs)
AND
polymorphism
AND
(colon OR intestine OR colorectal OR rectum)
AND
("case control" OR case-control OR cohort OR risk)))
21
Methods: Selection of Papers
Inclusion:
• Observational studies relating Cox polymorphisms to colon cancer or adenoma;
Exclusion:
• Studies focused on non-human subjects;
• Studies in languages besides English, French, Spanish or Portuguese;
Methods: Inclusion and Exclusion Criteria
Data base: Medline PubMed/Scopus
Abstracts
N=69
Scopus Medline
Excluded Included
N=21 N=48
N=6 N=7
Articles
N=13
Abstracts not included
N=46
Methods: Variables
Title Authors Journal Year of publication
Polymorphism
Laboratory methodology
Quality
Type of study and duration Selection methods Number of individuals Age Gender distribution Location of the study Ethnic origin
Publication:
Studies:
Procedures:
Description of articles included Type of study
n Male (%) Age (mean)
Ethnic Groups
Laboratory
methodology
Polymorphism Quality (out of
38)
Sansbury L,2006
Case-control 566 48 - Caucasians PCR - 27
Ali I,
2005
Case-control 1455 69 - - PCR Poli-768; -5229; -8494
22
Ulrich C, 2005
Case-control 1264 - - Americans Genotyping PTGS2.401; 926; 1629; 3050; 5209; 8473; 9850; 10335
24
Moreno V, 2004
Case-control 566 53 - - - R&W; L15-L16del; P17L;
L237M
29
Ulrich C, 2004
Cohort 1487 46 53 - - - 31
Koh W, 2004
Cohort 1487 46 60 Chinese PCR - 23
Lin H,
2002
Case-control 380 49 63 Various PCR - 33
Results:
Risk of adenoma
Risk of adenocarcinoma
Conclusion:
• Any conclusion on the risk of adenoma or adenocarcinoma related to Cox polymorphisms is precocious.
• The heterogeneity found may be related to differences in function of polymorphisms and types of study.
• Further studies with adequate design should address to the polymorphisms with the most significant results.