Genetic polymorphisms of Cox enzyme

and risk of colon adenoma and carcinoma:

A systematic review

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Faculdade de Medicina da Universidade do Porto

Ana Filipa Lima; Ana Teresa Pinheiro; Hugo André Mac edo; Filipa Bazenga Fernandes; João Artur Coimbra; Lúcia Elisa Guedes; Mara Vaness a Fernandes; Miguel Pinto Freitas; Patrícia Manuela Marques; Rui Fernando Castro; Sara Sofia Gouveia; Telma Anita Brito; Mário Dinis Ribeiro.

Supervisor: Prof. Doutor Altamiro Costa Pereira

� Introduction

� Aim

� Methods� Type of study� Papers selection� Inclusion and exclusion criteria definition� Extraction of specific data from the articles

Summary

• Cancer is the second leading cause of death

Faculdade de Medicina da Universidade do Porto

(Robbins Basic Pathology, 2003)

• Colon cancer is the second cause of cancer related with deaths in Portugal

(IARC, 2002)

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Introduction

(IARC, Portuguese population (Vila Nova de Gaia),1995)

• The colon is host to more primary neoplasms than any other organ in the body

• Colon cancer increaseswithin age both in male as female

• Male are the most afected

(Robbins Basic Pathology, 2003)

Introduction

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• Neoplasia can be defined as a group of cells that begin growing in an uncoordinated manner.

• Neoplasm cells compete with normal cells for their metabolic needs and enjoy a certain degree of autonomy

• Adenomas are neoplastic polyps that range from small tumors to large lesions

(Robbins Basic Pathology, 2003)

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Introduction

• Polyp is a tumorous mass that projects above a mucosal surface to form a macroscopically visible structure

• Genetic polymorphisms are related to changes in one nucleotide or a sequence of nucleotides in DNA.

(Robbins Basic Pathology, 2003))

(www1.lf1.cuni.cz )

Introduction

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(Google)

There are strong evidences that connect a cronicalinflamatory reaction to the development of neoplasias.

Reactive Intermediates ofoxygen and nitrogen

released

DNA damage

Polimorfisms in genes…IL-

1β, IL-6, TNF-α, CXCL,

CCR, COXCOX--22

(Immunology ,2003)

Prostaglandins

(Presentation by an expert)

Introduction

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• COX enzymes (cyclooxygenase enzyme) are produced by thebody in response to inflammation and by precancerous andcancerous tissues

(Biology queensu)

(Robbins Basic Pathology, 2003)

Introduction

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• To estimate the risk of colon adenoma or adenocarcinoma among individuals with Cox polymorphisms

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Aims

Cohort StudiesCase-controlStudies

Observationalstudies

Systematic review

Risk

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Methods: Type of study

• Database search using Medline PubMed:

Methods: Papers Selection

46

((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[MeSHTerms] 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)

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• Database search using Scopus:

2

(TITLE-ABS-KEY("COX polymorphisms") AND TITLE-ABS-KEY(risk of cancer)) ANDSUBJAREA(mult OR agri OR bioc OR immu OR neur OR phar OR mult OR medi OR nurs

OR vete OR dent OR heal)

25

(TITLE-ABS-KEY(“risk of colon cancer”)ANDTiTLE-ABS-KEY(genetic polymorphisms)ANDSUBJAREA(mult OR agri OR bioc OR immu OR neur OR phar OR mult OR medi OR nursOR vete OR dent OR heal)

Data base: Venn diagram

Medline PubMed

Scopus

45 1 26

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Inclusion:

• Observational studies relating Cox polymorphisms with colon cancer or adenoma;

Exclusions:

• Studies focused in non-human subjects;• Studies in languages besides English, French, Spanish or

Portuguese;

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Methods: Inclusion and Exclusion Criteria definition

Query

N=73

Not included:

N=54

• Cox enzyme is notmentioned;

• There are no relationsbetween Cox enzyme andcolon cancer;

• Not an observational study;

Excluded:

N=0

Data base: Medline PubMed/Scopus

Query

N=19

Query

N=19

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– Year of publication;– Year of study;

– Local of the study;– Type of study;– Race of individuals; – Age of individuals;– Number of patients;

Data to be extracted

- Table 2x2

With and without Coxpolymorphisms;

Proportions ofadenomas andadenocarcinomas

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