Shobab Leila, Burman Kenneth D, Wartofsky Leonard
MedStar Washington Hospital Center, Washington, District of Columbia, USA.
Medstar Health Research Institute, Washington, District of Columbia, USA.
Thyroid. 2022 Mar;32(3):224-235. doi: 10.1089/thy.2021.0361.
Sex dimorphism strongly impacts tumor biology, with most cancers having a male predominance. Uniquely, thyroid cancer (TC) is the only nonreproductive cancer with striking female predominance with three- to four-fold higher incidence among females, although males generally have more aggressive disease. The molecular basis for this observation is not known, and current approaches in treatment and surveillance are not sex specific. Although TC has overall good prognosis, 6-20% of patients develop regional or distant metastasis, one third of whom are not responsive to conventional treatment approaches and suffer a 10-year survival rate of only 10%. More efficacious treatment strategies are needed for these aggressive TCs, as tyrosine kinase inhibitors and immunotherapy have major toxicities without demonstrable overall survival benefit. Emerging evidence indicates a role of sex hormones, genetics, and the immune system in modulation of both risk for TC and its progression in a sex-specific manner. Greater understanding of the molecular mechanisms underlying sex differences in TC pathogenesis could provide insights into the development of sex-specific, targeted, and effective strategies for prevention, diagnosis, and management. This review summarizes emerging evidence for the importance of sex in the pathogenesis, progression, and response to treatment in differentiated TC with emphasis on the role of sex hormones, genetics, and the immune system.
性别二态性对肿瘤生物学有强烈影响，大多数癌症在男性中更为常见。独特的是，甲状腺癌（TC）是唯一一种非生殖系统癌症，女性发病率显著高于男性，女性发病率是男性的三到四倍，尽管男性的疾病通常更具侵袭性。这种现象的分子基础尚不清楚，目前的治疗和监测方法并非针对性别。虽然甲状腺癌总体预后良好，但6%至20%的患者会发生局部或远处转移，其中三分之一对传统治疗方法无反应，10年生存率仅为10%。对于这些侵袭性甲状腺癌，需要更有效的治疗策略，因为酪氨酸激酶抑制剂和免疫疗法有严重毒性，且未显示出总体生存获益。新出现的证据表明，性激素、遗传学和免疫系统在以性别特异性方式调节甲状腺癌风险及其进展方面发挥作用。深入了解甲状腺癌发病机制中性别差异的分子机制，有助于制定性别特异性、靶向性和有效的预防、诊断及管理策略。本综述总结了新出现的证据，强调了性别在分化型甲状腺癌发病机制、进展及治疗反应中的重要性，重点关注性激素、遗传学和免疫系统的作用。
