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

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.