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.