Gender is an age-specific effect modifier for papillary cancers of the thyroid gland

Abstract

Background: Thyroid cancer incidence rates have increased worldwide for decades, although more for papillary carcinomas than other types and more for females than males. There are few known thyroid cancer risk factors except female gender, and the reasons for the increasing incidence and gender differences are unknown.

Methods: We used the National Cancer Institute's Surveillance, Epidemiology, and End Results 9 Registries Database for cases diagnosed during 1976-2005 to develop etiological clues regarding gender-related differences in papillary thyroid cancer incidence. Standard descriptive epidemiology was supplemented with age-period-cohort (APC) models, simultaneously adjusted for age, calendar-period and birth-cohort effects.

Results: The papillary thyroid cancer incidence rate among females was 2.6 times that among males (9.2 versus 3.6 per 100,000 person-years, respectively), with a widening gender gap over time. Age-specific rates were higher among women than men across all age groups, and the female-to-male rate ratio declined quite consistently from more than five at ages 20-24 to 3.4 at ages 35-44 and approached one at ages 80+. APC models for papillary thyroid cancers confirmed statistically different age-specific effects among women and men (P < 0.001 for the null hypothesis of no difference by gender), adjusted for calendar-period and birth-cohort effects.

Conclusion: Gender was an age-specific effect modifier for papillary thyroid cancer incidence. Future analytic studies attempting to identify the risk factors responsible for rising papillary thyroid cancer incidence should be designed with adequate power to assess this age-specific interaction among females and males.

Figure 1. Papillary thyroid cancer incidence rates in the SEER 9 database by gender

A) Age-adjusted trends, 1976–80 to 2001–05. B) Age-specific incidence rates for females and males during 1976–2005 in the SEER 9 database.

Figure 2. Age-specific incidence rates for females and males by calendar period and birth cohort (SEER 9: 1976–2005)

A) Female rates stratified by calendar period year of diagnosis. B) Male rates stratified by calendar period year of diagnosis. C) Female rates stratified by cohort year of birth. D) Male rates stratified by cohort year of birth.

Figure 3. APC fitted age-at-onset curves and age-specific trends for females and males

A) Fitted age-at-onset curves derived for females and males with papillary thyroid cancer from 1976–2005. B) Age-specific temporal trends and net drift among females. C) Age-specific temporal trends and net drift among males. See text for further details.

Figure 4. Age-specific female-to-male incidence rate ratios (IRR_FM)

for the periods of diagnosis, 1976–80 to 2001–05, and the average over the six 5-year periods.