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

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.