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

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.

The case-case-time-control study design / 中华流行病学杂志

Although the ‘self-matched case-only studies' (such as the case-cross-over or self-controlled case-series method) can control the time-invariant confounders (measured or unmeasured) through design of the study,however,they can not control those confounders that vary with time.A bidirectional case-crossover design can be used to adjust the exposure-time trends.In the areas of pharmaco-epidemiology,illness often influence the future use of medications,making a bidirectional study design problematic.Suissa' s case-time-control design combines the case-crossover and the case-control design which could adjust for exposure-trend bias,but the control group may reintroduce selection bias,if the matching does not go well.We propose a "case-case-time-control" design which is an extension of the case-time-control design.However,rather than using a sample of external controls,we choose those future cases as controls for current cases to counter the bias that arising from temporal trends caused by exposure to the target of interest.In the end of this article we will discuss the strength and limitations of this design based on an applied example.