Advancing environmental epidemiologic methods to confront the cancer burden

Abstract

Even though many environmental carcinogens have been identified, studying their effects on specific cancers has been challenging in nonoccupational settings, where exposures may be chronic but at lower levels. Although exposure measurement methods have improved considerably, along with key opportunities to integrate multi-omic platforms, there remain challenges that need to be considered, particularly around the design of studies. Cancer studies typically exclude individuals with prior cancers and start recruitment in midlife. This translates into a failure to capture individuals who may have been most susceptible because of both germline susceptibility and higher early-life exposures that lead to premature mortality from cancer and/or other environmentally caused diseases like lung diseases. Using the example of breast cancer, we demonstrate how integration of susceptibility, both for cancer risk and for exposure windows, may provide a more complete picture regarding the harm of many different environmental exposures. Choice of study design is critical to examining the effects of environmental exposures, and it will not be enough to just rely on the availability of existing cohorts and samples within these cohorts. In contrast, new, diverse, early-onset case-control studies may provide many benefits to understanding the impact of environmental exposures on cancer risk and mortality. This article is part of a Special Collection on Environmental Epidemiology.

Keywords: cancer; environmental carcinogens; environmental epidemiology; genetic susceptibility; study design.

Figure 1

Theoretical age distribution (A) and mutational burden (B) of incident cancers in a cohort study with recruitment in midlife. The graph shows the age distribution of incident cancer cases in a hypothetical cohort with recruitment from age 40 years to age 64 years, assuming equal recruitment numbers for each age group (40-44, 45-49, 50-54, 55-59, and 60-64 years). Age-specific cancer incidence rates are estimated using age-specific cancer incidence data from the Centers for Disease Control and Prevention’s National Program of Cancer Registries and the Surveillance, Epidemiology, and End Results program (2001-2019 data representative of all 50 US states). A) Example of age distribution of incident cancer cases in a cohort with recruitment at ages 40-64 years; B) distribution of germline and somatic mutations by age group at diagnosis (adapted from Qing et al⁹⁹). The germline variant burden in cancer genes correlates with age at diagnosis and somatic mutation burden.

Figure 2

Schematic overview of cohorts enriched for cancer susceptibility, environmental exposures, or neither.

Figure 3

Applications of the case-control study design for studying environmental exposures and cancer.

Figure 4

Approaches for environmental epidemiology across the cancer control continuum.