ORF12-08 - Reproductive Milestones and Thyroid Cancer Risk in Women: Evidence from a Nationwide Cohort

Background

Thyroid cancer occurs more frequently in women than in men, suggesting a potential role of reproductive and hormonal factors in thyroid carcinogenesis. However, epidemiologic evidence regarding the association between female reproductive factors and thyroid cancer risk remains inconsistent.

Methods

We conducted a population-based retrospective cohort study using data from the Korean National Health Insurance Service (NHIS), which provides universal health insurance coverage to the entire Korean population and contains comprehensive healthcare information. The study population comprised women aged ≥40 years who participated in the national breast and cervical cancer screening programs between 2010 and 2011, during which reproductive factors were collected using standardized questionnaires. Incident thyroid cancer was identified using the International Classification of Diseases, 10th Revision (ICD-10) code C73 in NHIS claims data. Participants were followed until the diagnosis of thyroid cancer, death, or the end of follow-up in 2023. Because the NHIS covers the entire population, loss to follow-up was negligible. Associations between reproductive factors and the incidence of thyroid cancer were evaluated using Cox proportional hazards regression models. Multivariable models were adjusted for age, smoking status, alcohol consumption, regular physical activity, body mass index, hypertension, diabetes mellitus, dyslipidemia, history of cancer, and household income level.

Results

A total of 5,659,432 women were included in the analysis. During follow-up, the incidence rate of thyroid cancer was 2.4 per 1,000 person-years. A longer reproductive span was associated with a progressively increased risk of thyroid cancer, with adjusted hazard ratios (HRs) of 1.09 (95% CI, 1.06–1.12) for ≥30 years, 1.19 (95% CI, 1.16–1.22) for ≥35 years, and 1.30 (95% CI, 1.25–1.35) for ≥40 years. Use of hormone replacement therapy (HRT) was also associated with an increased risk of thyroid cancer, with a stronger association observed among women who received HRT for ≥5 years (HR, 1.25; 95% CI, 1.19–1.31). Although parity did not show a clear association with thyroid cancer risk, a history of lactation was associated with a reduced risk, particularly among women who breastfed for ≥1 year (HR, 0.94; 95% CI, 0.90–0.98).

Conclusions

Female reproductive factors were associated with thyroid cancer risk, supporting a potential role of cumulative endogenous hormonal exposure in thyroid carcinogenesis. These findings may help explain the marked female predominance of thyroid cancer and provide insights into risk stratification based on reproductive history.

[This research was supported by the Basic Science Research Program through a grant from the National Research Foundation of Korea (NRF) funded by the Ministry of Education (RS-2023-00245534).]