Molecular Epidemiology and Biomarkers in Etiologic Cancer Research: The New in Light of the Old

Abstract

The purpose of this review is to evaluate progress in molecular epidemiology over the past 24 years in cancer etiology and prevention to draw lessons for future research incorporating the new generation of biomarkers. Molecular epidemiology was introduced in the study of cancer in the early 1980s, with the expectation that it would help overcome some major limitations of epidemiology and facilitate cancer prevention. The expectation was that biomarkers would improve exposure assessment, document early changes preceding disease, and identify subgroups in the population with greater susceptibility to cancer, thereby increasing the ability of epidemiologic studies to identify causes and elucidate mechanisms in carcinogenesis. The first generation of biomarkers has indeed contributed to our understanding of risk and susceptibility related largely to genotoxic carcinogens.Consequently, interventions and policy changes have been mounted to reduce risk from several important environmental carcinogens. Several new and promising biomarkers are now becoming available for epidemiologic studies, thanks to the development of highthroughput technologies and theoretical advances in biology. These include toxicogenomics, alterations in gene methylation and gene expression, proteomics, and metabonomics, which allow large-scale studies, including discovery-oriented as well as hypothesis-testing investigations. However, most of these newer biomarkers have not been adequately validated, and their role in the causal paradigm is not clear. There is a need for their systematic validation using principles and criteria established over the past several decades in molecular cancer epidemiology. (Cancer Epidemiol Biomarkers Prev 2007;16(10):1954 -65)

A serum nuclear magnetic resonance-based metabolomic signature of advanced metastatic human breast cancer

“…Breast cancer displays a high heterogeneity in terms of etiology and histology as well as prognosis, metastatic evolution and response to treatments. Deciphering the molecular basis of such heterogeneity is a major challenge, now achievable through new bio-molecular and analytical techniques, aiming at a comprehensive cancer characterization for risk stratification, therapeutic target identification and appropriate treatment selection [2].…”

Combined exposure to X-irradiation followed by N-ethyl-N-nitrosourea treatment alters the frequency and spectrum of Ikaros point mutations in murine T-cell lymphoma

“…Molecular epidemiological data for human cancers have been analyzed to establish causation, and several chemical carcinogen signatures have been identified [43][44][45][46]. However, only a limited number of controversial radiation signatures have been reported in human cancers, such as a p53 mutation in lung tumors of miners heavily exposed to radon [47] and a possible distinct pattern of RET oncogene rearrangement in post-Chernobyl thyroid tumors [48].…”

The Mediterranean Diet and Breast Cancer Risk

“…Elucidation of the mechanisms involved will aid in the identification of biomarkers of the exposure as well as biomarkers of the disease: these findings will in turn add weight to the association helping researchers assign causality. Vineis and Perera [50] propose the use of complementary study designs to establish new biomarkers that lie on the causal pathway between exposure and disease. For example, identification of biomarkers that in prospective studies are shown to be associated with adherence to the Mediterranean diet and evidence from nested case-control studies that these same biomarkers are predictive of breast cancer risk, will be sufficient to classify these biomarkers as part of the mechanistic pathway linking exposure to disease and to regard this association as causal (Figure 4).…”