Obesity Is Associated with BRAFV600E-Mutated Thyroid Cancer

Abstract

Background: Thyroid cancer incidence has increased in many parts of the world since the 1980s, as has the prevalence of obesity. Evidence suggests that people with greater body size have higher thyroid cancer risk. However, it is unclear whether this association is causal or is driven by over-diagnosis of indolent cancers, because overweight/obese people use health services more frequently than those of normal weight, thus conferring greater opportunity for incidental diagnosis. Assessing whether obesity is associated with higher-risk thyroid cancers might help clarify this issue. Methods: We recruited 1013 people diagnosed with thyroid cancer between 2013 and 2016 and 1057 population controls, frequency matched by sex and age group. We used logistic regression to assess the association between body mass index (BMI) and overall thyroid cancer risk as well as by tumor BRAF mutational status as a marker of potentially higher-risk cancer. Results: Overall, obesity was associated with greater risk of thyroid cancer (odds ratio [OR] = 1.72; 95% confidence interval [CI 1.37-2.16] for obese vs. normal BMI). The association with obesity was significantly stronger for BRAF-mutation positive than BRAF-negative papillary thyroid cancers (PTCs; OR = 1.71 [CI 1.17-2.50] for BRAF-positive vs. BRAF-negative cancers). The increased risks associated with overweight/obesity did not vary by histological subtypes or presence/absence of adverse tumor histologic features. Conclusions: Greater risk of BRAF-mutated PTCs among those with high BMI suggests that the association may not merely reflect greater health care service use and indicates an independent relationship between obesity and clinically important thyroid cancer.

Keywords: BRAF mutation; body mass index; obesity; over-diagnosis; thyroid cancer.