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 COX-2 Polimorfisms in genes…IL- 1β, IL-6, TNF-α, CXCL, CCR, COX-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 Studies Case-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 ScopusMedline ExcludedIncluded 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 nMale (%)Age (mean) Ethnic Groups Laboratory methodology PolymorphismQuality (out of 38) Sansbury L,2006 Case-control56648-CaucasiansPCR-27 Ali I, 2005 Case-control PCRPoli-768; -5229; Ulrich C, 2005 Case-control1264--AmericansGenotypingPTGS2.401; 926; 1629; 3050; 5209; 8473; 9850; Moreno V, 2004 Case-control R&W; L15- L16del; P17L; L237M 29 Ulrich C, 2004 Cohort Koh W, 2004 Cohort ChinesePCR-23 Lin H, 2002 Case-control VariousPCR-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.