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

Given the female predominance of thyroid cancer, particularly in the reproductive age range, female sex hormones have been proposed as an etiology; however, previous epidemiological studies have shown conflicting results. We conducted a pooled analysis using individual data from nine prospective cohorts in the Asia Cohort Consortium to explore the association between 10 female reproductive and hormonal factors and thyroid cancer risk. Using Cox proportional hazards models, cohort-specific hazard ratios (HR) and 95% confidence intervals (CI) were estimated and then pooled using a random-effects model. Analyses were stratified by country, birth years, smoking status, and body mass index, and thyroid cancer risk based on age of diagnosis was also examined. Among 259,649 women followed up for a mean of 17.2 years, 1,353 incident thyroid cancer cases were identified, with 88% (n = 1,140) being papillary thyroid cancer. Older age at first delivery (>= 26 vs. 21-25 years) was associated with increased thyroid cancer 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 thyroid cancer 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 thyroid cancer 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 nonsignificant inverse associations for China and Japan. Contextual and macrosocial changes in reproductive factors in Asian countries may influence thyroid cancer risk. Prevention Relevance: This analysis of prospective cohort studies across three Asian countries highlights that older age at first birth is linked to increased thyroid cancer risk. As women delay motherhood, understanding these trends is vital for public health strategies addressing reproductive factors influencing thyroid cancer risk in these populations.