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01.12.2015 | Research article | Ausgabe 1/2015 Open Access

BMC Public Health 1/2015

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

BMC Public Health > Ausgabe 1/2015
Rafael Meza, Joanne T. Chang
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s12889-015-2108-4) contains supplementary material, which is available to authorized users.

Competing interests

The authors declared that they have no competing interests.

Authors’ contributions

JTC performed the analysis, analyzed the results and drafted the manuscript; R.M. conceived the study, analyzed the results and drafted the manuscript. All authors read and approved the manuscript.



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.
Additional file 1: Table S1. Trends of thyroid cancer incidence by gender, race, histology and stage –Joinpoint analyses 1973-2010. Figure S1. Thyroid cancer incidence period and cohort trends by gender and stage – TSCE-P-C thyroid cancer model. Figure S2. Thyroid cancer age-adjusted incidence rates by gender, race and stage. Table S2. Akaike information criteria (AIC*) values for Age-Period-Cohort models relative to the AC model**. Figure S3. Age effects by race and sex (all cases)- Age-period-cohort models. Figure S4. Age-effects by tumor stage (all cases)- Age-period-cohort models. Figure S5. Thyroid cancer incidence period and cohort trends by gender and race – Age-period-cohort models. Figure S6. Thyroid cancer incidence period and cohort trends by gender and stage – Age-period-cohort models. Figure S7. Observed versus fitted thyroid cancer incidence by gender in Whites. Figure S8. Observed versus fitted thyroid cancer incidence by gender in Blacks. Figure S9.Observed versus fitted thyroid cancer incidence among papillary histology by gender. Figure S10. Observed versus fitted thyroid cancer incidence among follicular histology by gender. (PDF 1164 kb)
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