Multistage carcinogenesis and the incidence of thyroid cancer in the US by sex, race, stage and histology

Rafael Meza, Joanne T. Chang

Thyroid cancer has the fastest growing incidence in the US. However, the underlying causes are still under debate. We analyzed thyroid cancer incidence in the SEER-9 registry from 1973-2010 using multistage carcinogenesis and age-period-cohort models. Multistage models were used to investigate differences in initiation, promotion and malignant conversion rates of thyroid tumors by sex, race, stage, and histology. Models were adjusted for period and cohort trends to investigate the contributions of each factor, and determine whether birth- or diagnosis-year better correlate with observed incidence patterns. Significant increases in thyroid cancer incidence by period or calendar-year were found for all sex, race, stage and histology combinations, particularly for localized cases (a 3- and 4-fold increase from 1973-2010 for females and males, respectively). Multistage analyses suggest that the 3-fold higher incidence in women could be explained by 1.5-fold higher initiation and promotion rates. Analyses by race suggest that the lower incidence in blacks can be attributed to lower promotion rates versus whites. Analysis by histology showed considerable decreases in follicular cancer incidence by birth-cohort since the early 1900s. Multistage modeling suggests that variations in thyroid cancer initiation and promotion can explain the observed differences in incidence by sex, race and histology. The consistent increases in incidence by calendar-year for all sex-race-histology-stage combinations suggest that the rise may be predominantly due to more intensive screening-diagnostics, although an environmental factor may be also at play. Our analyses constitute a first step towards the development of thyroid cancer natural history models.