Perinatal Risk Factors of Pediatric and Early-Onset Thyroid Cancer: A Population-Based Record-Linkage Study in California
Nicole C. Deziel, Rong Wang, Kai Chen, Joshua L. Warren, Xin Meng, Catherine A. Dinauer, Joseph L. Wiemels, Catherine Metayer, Xiaomei MaBackground:
Thyroid cancer is the second most common cancer among individuals <40 years. The young diagnosis age and slow tumor growth suggest that early-life factors may contribute to risk.
Methods:
We conducted a population-based nested case–control study within a cohort of individuals <40 years old born in California, United States (1982–2017), using linked birth and cancer registry data. The study included 5670 patients diagnosed with their first primary thyroid cancer at age 0–39 years (pediatric: age 0–19; early-onset: age 20–39) and 283,500 birth-year-matched controls (1:50). Multivariable conditional logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) for associations between birth and parental characteristics and thyroid cancer incidence overall and stratified by diagnosis age (0–19, 20–39 years), histological subtypes (papillary, follicular, medullary), and ethnicity (non-Hispanic White, Hispanic).
Results:
In the overall population, females had four times higher odds of thyroid cancer compared with males (OR: 4.00, 95% CI: 3.75–4.27), consistent with prior literature. Higher birth weight was associated with increased odds of thyroid cancer overall (OR per 500 g: 1.05, 95% CI: 1.02–1.08) and across age groups, histological subtypes, and ethnicities. Increased odds were also seen in relation to higher maternal educational attainment, higher parental ages, and lower neighborhood social vulnerability, factors linked to higher socioeconomic status. Hispanic ethnicity and maternal foreign-born status were associated with increased risk, factors sometimes correlated with greater social disadvantage. Inverse associations were observed for higher birth order and Black (vs. non-Hispanic White) individuals. Age-stratified analyses were similar except for social vulnerability, which was positively associated among pediatric cases (OR: 1.28; 95% CI: 1.09–1.50) but inversely associated among early-onset cases (OR: 0.83; 95% CI: 0.76–0.90). Results stratified by histological subtype were generally consistent with the overall results or null. Most risk factors, including maternal foreign-born status, remained in ethnicity-based strata.
Conclusions:
Multiple perinatal factors were associated with pediatric and early-onset thyroid cancer, underscoring the importance of the early-life time window. Consistent relationships between birth weight and thyroid cancer support a role for