Tobacco smoking and risk of thyroid cancer according to BRAFV600E mutational subtypes

Clin Endocrinol (Oxf). 2021 Dec;95(6):891-900. doi: 10.1111/cen.14545. Epub 2021 Jul 4.

Abstract

Objective: Smoking has been associated with a reduced risk of thyroid cancer, but whether the association varies between higher- and lower-risk cancers remains unclear. We aimed to assess the association between smoking and risk of thyroid cancer overall as well as by tumour BRAF mutational status as a marker of potentially higher-risk cancer.

Design and patients: We recruited 1013 people diagnosed with thyroid cancer and 1057 population controls frequency-matched on age and sex.

Methods: Multivariable logistic regression was used to assess the association overall and in analyses stratified by tumour characteristics. We used sensitivity analysis to assess the potential for selection bias.

Results: We found little evidence of an association with current smoking (odds ratio [OR] = 0.93; 95% confidence interval [CI]: 0.69-1.26; current vs. never smoking), but a higher number of pack-years of smoking was associated with a lower risk of thyroid cancer (OR = 0.75; 95% CI: 0.57-0.99; ≥20 pack-years vs. never). However, after correcting for potential selection bias, we observed a statistically significant inverse association between current smoking and risk of thyroid cancer (bias-corrected OR = 0.65; 95% CI: 0.51-0.83). Those with BRAF-positive cancers were less likely to be current smokers than those with BRAF-negative cancers (prevalence ratio: 0.79; 95% CI: 0.62-0.99).

Conclusion: We found smoking was inversely related to thyroid cancer risk and, in particular, current smoking was associated with a reduced risk of potentially more aggressive BRAF-positive than the likely more indolent BRAF-negative papillary thyroid cancers.

Keywords: BRAF-mutation; bias analysis; population-based sample; thyroid cancer; tobacco smoking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Logistic Models
  • Proto-Oncogene Proteins B-raf* / genetics
  • Thyroid Cancer, Papillary
  • Thyroid Neoplasms* / etiology
  • Thyroid Neoplasms* / genetics
  • Tobacco Smoking

Substances

  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf