The role of gene–environment interaction in the aetiology of human cancer: examples from cancers of the large bowel, lung and breast

Abstract

1 It has become increasingly clear that cancer can be considered neither purely genetic nor purely environmental. A relatively new area of cancer research has focused on the interaction between genes and environment in the same causal mechanism. Primary candidates for gene-environment interaction studies have been genes that encode enzymes involved in the metabolism of established cancer risk factors. There are common variant forms of these genes (polymorphisms), which may alter metabolism and increase or decrease exposure to carcinogens, thus impacting the risk of cancer. We present an overview of enzymes involved in carcinogen metabolism, present epidemiological tools to evaluate gene-environment interactions, and provide examples from cancers of the breast, lung and large bowel.

Relationship between genetic polymorphisms of metabolizing enzymes CYP2E1, GSTM1 and Kazakh’s esophageal squamous cell cancer in Xinjiang, China

“…In recent years, a relatively new field of cancer research has focused on the interaction between genes and environment to understand the etiology of cancer [1] . Primary candidates for gene-environment interaction studies are those which encode enzymes related to the metabolism of established cancer risk factors.…”

Gene-environment interactions in sarcoidosis: challenge and opportunity

“…Statistical gene-environment relationships might be categorized by defining them as requisite vs. modifier and additive vs. multiplicative [16,17]. All these relationships are likely to be present in sarcoidosis, a complex human disease with multiple genetic and environmental modifiers.…”

The Sociobiologic Integrative Model (SBIM): Enhancing the Integration of Sociobehavioral, Environmental, and Biomolecular Knowledge in Urban Health and Disparities Research

“…31 Finally, other indirect inputs, such as genetic polymorphisms of tumor-associated genes, operate at the cellular or molecular level, impacting gene function or expression (see BLUNG CANCER AND THE SBIM^discussion below). 17,32,33,[33][34][35][36][37][38][39] The specific group of direct and indirect inputs to which an individual is exposed may be highly variable between individuals or populations. Ultimately, it is determined by the sociocultural milieu or surroundings in which the individual lives, works, and socializes.…”

“…These systems include, but are not limited to, the N-acetyltransferase enzymes, the phase I cytochrome p450 (CYP) system, and the phase II glutathione-S-transferase (GST) system. 34 Although there are potentially many such systems operating in the body, the absolute number is finite. Integratively understanding health requires that the combined effects of all inputs (direct and indirect) be understood in the context of their impact on biologic processes.…”