Association of Preexisting Thyroid Autoimmunity With Risk of Papillary Thyroid Cancer

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In a case-control study among U.S. active-duty personnel reported in the Journal of Clinical Oncology, McLeod et al found that preexisting thyroid autoimmunity was associated with an increased risk of developing papillary thyroid cancer. 

The study included 451 randomly selected personnel serving between 1996 and 2014 with a diagnosis of papillary thyroid cancer and stored serum samples collected 7 to 10 years prior to the date of diagnosis (index date) who were sex- and age-matched with 451 controls without a cancer diagnosis; controls were assigned the same index date. Thyroid peroxidase antibody status in serum was assessed for relationship to risk of cancer diagnosis. 

Key Findings

Among the 451 cases of papillary thyroid cancer and matched controls (median age = 36 years, 61.4% men), thyroid peroxidase antibody positivity vs negativity at 7 to 10 years prior to index data was associated with an increased risk of thyroid cancer (odds ratio [OR] = 1.90, 95% confidence interval [CI] = 1.33–2.70). Exploratory analysis indicated an increasing risk with increasing thyroid peroxidase antibody titer; odds ratios were 2.95 (95% CI = 1.37–6.36) with titers of 550 to 1,399 IU/mL and 3.91 (95% CI = 1.66–9.24) with titers ≥ 1,400.

Exploratory analysis showed that thyroid peroxidase positivity was associated with greater risk among women (OR = 2.48, 95% CI = 1.35–4.54) than men (OR = 1.62, 95% CI = 1.03–2.55). However, the interaction term was not significant (P = .22).

Overall, 85% of cases (379 of 451) had a thyroid-related diagnosis recorded prior to their index date. In analysis including only cases with no history of thyroid autoimmunity diagnosis, the adjusted odds ratio for thyroid peroxidase antibody positivity 7 to 10 years pre–index date was 1.61 (95% CI = 1.06–2.44). In mediation analysis, a significant direct effect of thyroid peroxidase antibody status 7 to 10 years pre–index date was observed (OR = 1.59, 95% CI = 1.09–2.31), with it being estimated that approximately 35% of the total effect (OR = 2.03, 95% CI = 1.39–2.96) was mediated by contemporaneous diagnosis of autoimmunity.  

Cases with a diagnosis of autoimmunity vs no diagnosis had smaller tumor size, with 58% of cancers being ≤ 10 mm in diameter.

The investigators concluded, “Longstanding prior thyroid autoimmunity up to 10 years before thyroid cancer diagnosis was associated with papillary thyroid cancer risk. The results could not be fully explained by diagnosis of thyroid autoimmunity, although when autoimmunity had been identified, thyroid cancers were diagnosed at a very early stage.”

Donald S.A. McLeod, MBBS, PhD, of the Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the National Health and Medical Research Council of Australia, Walton Family Foundation, and others. For full disclosures of the study authors, visit

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