Fifty years of comprehensive cancer hazard identification: the IARC {Monographs} Programme’s systematic review and synthesis across multiple evidence streams

Abstract

BACKGROUND AND AIM: For the past 50 years, the {Monographs} Programme of the International Agency for Research on Cancer (IARC) has provided the world’s most comprehensive compendium of cancer hazard identification. More than 1020 agents have been evaluated by the {Monographs}, selected based on evidence of human exposure and of carcinogenicity. These agents comprise chemicals, physical and biological agents, complex mixtures, occupational exposure circumstances, dietary factors, personal habits, and other exposures of everyday life. The aim of this presentation is to describe the comprehensive evidence synthesis used by the IARC {Monographs}. METHODS: Expert working groups are assembled by the {Monographs} scientific secretariat, based on expertise with the agent or relevant methodology, freedom from conflicts of interest, and diversity of scientific viewpoints and approaches. These working groups review and synthesize all publicly available evidence in three streams: human cancer, cancer in experimental animals, and carcinogen mechanisms. Evidence from these three streams is synthesized first within and then across streams, to reach an overall conclusion about whether the agent is {carcinogenic}, {probably carcinogenic}, {possibly carcinogenic}, or {not classifiable as to its carcinogenity} to humans. Exposure information about the agent is also characterized in each {Monograph}. RESULTS:Exposure settings for agents classified as {carcinogenic to humans} include the environment (e.g., air pollution), workplace (e.g., welding fumes), diet (e.g., processed meat), infections (e.g., human papilloma virus), medicines (e.g., estrogen-progestogen oral contraceptives), and personal habits (e.g, opium consumption). Recent advances made within this unique and influential program include comprehensive and transparent incorporation of systematic review principles, explicit consideration of the impact of exposure assessment quality in human cancer and mechanistic studies, and novel methods for mechanistic evidence evaluation. CONCLUSIONS:The systematic review process undertaken by IARC {Monographs} working groups is robust and well-accepted. Recent advances to increase transparency of expert decision-making provide a foundation for sound evidence synthesis into the future. KEYWORDS: Evidence synthesis, carcinogenicity, hazard identification, risk assessment, mechanisms, cancer