Active and Passive Smoking, BRAF(V600E) Mutation Status, and the Risk of Papillary Thyroid Cancer: A Large-Scale Case-Control and Case-Only Study

PURPOSE: The association between tobacco smoking and thyroid cancer remains uncertain. We evaluated the associations of active and passive smokingwith the risk of papillary thyroid cancer (PTC), the most common type of thyroid cancer, and with the BRAF(V600E) mutation, the most common oncogenic mutation in PTC related to poor prognosis. MATERIALS AND METHODS: We conducted this study with newly diagnosed PTC patients (n=2,142) and community controls (n=21,420) individually matched to cases for age and sex. Information on active and passive smoking and potential confounders were obtained from structured questionnaires, anthropometric measurements, and medical records. BRAF(V600E) mutation status was assessed in PTC patients. We evaluated the associations of active and passive smoking with PTC and BRAF(V600E) mutation risk using conditional and unconditional logistic regression models, respectively. RESULTS: We did not find associations between exposure indices of active and passive smoking and PTC risk in both men and women, except for the association between current smoking and lower PTC risk. Cumulative smoking ≥ 20 pack-years was associated with lower BRAF(V600E) mutation risk in male PTC patients (odds ratio [OR], 0.55; 95% confidence interval [CI], 0.30 to 1.00). The CI for the association was wider in female PTC patients (OR, 0.23; 95% CI, 0.02 to 2.62), possibly owing to a smaller sample size in this stratum. CONCLUSION: We did not find consistent associations between active and passive smoking and PTC risk. Cumulative smoking ≥ 20 pack-years was associated with lower BRAF(V600E) mutation risk in male PTC patients.