Infections and cancer: Established associations and new hypotheses

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Abstract

Around the world, infection is one of the most important causes of cancer. Almost one in every five malignancies can be attributed to infectious agents. Among infection-related neoplasms, cancers of the stomach, liver and cervix uteri detain the highest incidence figures, and are known to be largely attributable to Helicobacter pylori, hepatitis B and C viruses, and human papilloma virus, respectively. Other infectious organisms can also cause cancer; these include the Epstein-Barr virus (nasopharyngeal carcinoma, and different types of lymphoma), Human herpes virus-8 (Kaposi's Sarcoma), human T-cell leukemia virus type I (leukaemia, lymphoma), liver flukes (cholangiocarcinoma) and schistosomiasis (bladder cancer). Infection with human immunodeficiency virus, although strongly associated with an excess of cancer incidence at many cancer sites, is probably not carcinogenic per se, but acts mainly via immunodeficiency. The burden of infection-related cancers is still underestimated worldwide, due to the use of conservative population prevalence and risk ratio estimates. Furthermore, associations with new infectious agents remain yet to be explored.

Introduction

Around the world, infection is one of the most important causes of cancer [1]. It was estimated conservatively that in the year 2002, 18% of all malignancies were attributable to infectious agents [2]. Among infection-related neoplasms, cancers of the stomach, liver and cervix uteri detain the highest incidence figures, and are known to be largely attributable to Helicobacter pylori, hepatitis B and C viruses, and human papilloma virus, respectively. In terms of overall mortality, cancers of the stomach in men, and cervix uteri in women, rank second and third worldwide, while liver cancer ranks third and sixth for men and women, respectively [3].

Section snippets

H. pylori: the bacterium

H. pylori is a spiral shaped Gram negative bacterium that is transmitted from human to human, usually during early childhood, and colonizes the gastric epithelium for a lifetime in the absence of specific antimicrobial therapy. In industrialized countries, the improvement of sanitation and hygiene has been responsible for a dramatic decrease in transmission during the last few decades, and the epidemiology of the bacterium now typically follows a birth cohort model: older people (infected

Epstein-Barr virus (EBV)

EBV is a DNA virus of the herpes virus family that establishes a latent infection and life-long persistence in more than 90% of the population in the world. The virus is transmitted by saliva and initially infects the epithelium of the oropharynx, from which it spreads into B-cells of the lymphoid tissue [74]. Most primary EBV infections are subclinical. In developing countries 80% children are infected by the age of 3. In developed countries, primary infection is usually delayed until

Conclusion and new hypotheses

In epidemiology, a common definition of the attributable fraction is the proportion of disease occurrence that would potentially be eliminated if a specific exposure were prevented. Calculations based on relative risks from well conducted epidemiological studies and population prevalence data have led to the estimate that there would be 17.8% fewer cancers worldwide (26.3% in developing countries and 7.7% in developed countries) if chronic infections with known carcinogenic infectious agents

Conflict of interest

Catherine de Martel and Silvia Franceschi have no conflict of interest to declare.

Reviewers

Dr. Carlo La Vecchia, Istituto di Ricerche Farmacologiche Mario Negri, Via Eritrea, 62, I-20157 Milan, Italy.

Dr. Luigino Dal Maso, Centro di Riferimento Oncologico, Serv. Epidemiologia, Via Franco Gallini, 2, Aviano, PN, Italy.

Prof. Fabio Levi, IUMSP, CHUV, Cancer Epidemiology Unit, Rue du Bugnon 17, CH-1005 Lausanne, Switzerland.

Acknowledgment

The authors would like to thank S. Nouveau for editorial assistance.

Dr. Catherine de Martel received her medical degree from the Bichat-Claude Bernard University in Paris, France. After her residency, she joined the French National Agency for Research on AIDS (ANRS) as a research assistant for a few years. She then received a M.S. and a Ph.D. in infectious disease epidemiology from Stanford University School of Medicine, Stanford, California, and worked on Helicobacter pylori associated cancers in the department of Medicine. She now collaborates with the

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    Dr. Catherine de Martel received her medical degree from the Bichat-Claude Bernard University in Paris, France. After her residency, she joined the French National Agency for Research on AIDS (ANRS) as a research assistant for a few years. She then received a M.S. and a Ph.D. in infectious disease epidemiology from Stanford University School of Medicine, Stanford, California, and worked on Helicobacter pylori associated cancers in the department of Medicine. She now collaborates with the International Agency of Research on Cancer (IARC) on research projects involving infection-associated cancers.

    Dr. Silvia Franceschi received her medical degree from the University of Milan, Italy, where she was trained as a gynecologist. Since medical school, she has been interested in epidemiology and statistics, and obtained a post-graduate diploma in medical statistics from the University of Pavia and a M.S. from the Division of Epidemiology of the Imperial Cancer Research Fund, Oxford, UK. After having directed the Epidemiology Unit of the Aviano Cancer Center from 1984 to 2000, Dr. Silvia Franceschi became, in 2000, Head of the Infections and Cancer Epidemiology Group and, in 2004, coordinator of the Epidemiology and Biology Cluster at the International Agency for Research on Cancer (IARC), Lyon, France. In the context of IARC, she has chiefly been involved in studies on infectious diseases and cancer, most notably human papilloma virus and cervical and oral cancer, HIV and hepatitis C virus and lymphomas, and Helicobacter pylori and stomach cancer. All her studies involve broad international collaborations, mainly with Latin-America, Asia and Africa. Over the years she has closely collaborated with several research centers in the United States (National Cancer Institute) and Oxford, especially in respect to meta-analyses and pooled analyses (e.g., cancers of the breast, thyroid, and cervix).

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