Reproductive and Hormonal Factors and Thyroid Cancer Risk: Pooled Analysis of Prospective Cohort Studies in the Asia Cohort Consortium

Cancer Prev Res (Phila). 2025 Jan 23. doi: 10.1158/1940-6207.CAPR-24-0330. Online ahead of print.

Abstract

Given the female predominance of thyroid cancer (TC), particularly in the reproductive age range, female sex hormones have been proposed as an aetiology; however, previous epidemiological studies have shown conflicting results. We conducted a pooled analysis using individual data from 9 prospective cohorts in the Asia Cohort Consortium, to explore the association between 10 female reproductive and hormonal factors and TC risk. Using Cox proportional hazards models, cohort-specific hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated and then pooled using a random-effects model. Analyses were stratified by country, birth years, smoking status, body mass index, and TC risk based on age of diagnosis was also examined. Among 259,649 women followed for a mean 17.2 years, 1,353 incident TC cases were identified, 88% (n=1,140) being papillary TC. Older age at first delivery (≥26 vs 21-25 years) was associated with increased TC risk (p-trend=0.003, HR=1.16, 95% CI:1.03-1.31), particularly when diagnosed later in life (≥55 vs <55 years) [p-trend=0.003; HR=1.19, 95% CI:1.02-1.39]. Among younger birth cohorts, women with more number of deliveries showed an increased TC risk [p-trend=0.0001, HR=2.40, 95% CI:1.12-5.18 (≥5 vs 1-2 children)], and there was no substantial trend in older cohorts. Distinct patterns were observed for the number of deliveries and TC risk across countries, with a significant positive association for Korea [p-trend=0.0008, HR=1.89, 95% CI:1.21-2.94 (≥5 vs 1-2 children)], and non-significant inverse associations for China and Japan. Contextual and macrosocial changes in reproductive factors in Asian countries may influence thyroid cancer risk.