Several major cancer types exhibit significant sex dimorphism in incidence and survival. Whether and how sex as a biological factor impacts tumorigenesis, progression, and survival warrants full investigation, as such knowledge may lead to novel, precise prevention and treatment strategies. We reviewed epidemiological and molecular data on sex differences in cancers of the esophagus, bladder, head and neck, lung, liver, kidney, stomach, and skin melanoma, as well as the potential role of androgens and androgen receptor (AR) activity in these cancers. The potential molecular mechanisms are briefly discussed. Elevated testosterone (T) levels seemed to be associated with increased liver cancer and cutaneous melanoma incidences, and with reduced esophageal cancer risk. AR activity does not always correlate with T levels in tumorigenesis and progression. Higher AR expressions are associated with poorer survival in ESCC, whereas the role of AR in the survival of HNSCC and melanoma patients is inconsistent. The molecular impact of AR in liver cancer, kidney cancer, melanoma, and lung cancer is controversial. However, AR is likely to promote tumor growth and/or progression in esophagus, bladder, head and neck, and stomach cancers, and thus is associated with poor survival. Patients diagnosed with a tumor in this latter group could potentially benefit from therapeutic approaches targeting AR. Overall, the research on sex hormone androgens and AR in these cancers is limited. Further research is needed to determine a possible U-shaped relationship of T with cancer risk, and to decipher the role of testosterone and AR in some of these tumors to facilitate our understanding of sex dimorphism and to explore novel T/AR-based treatment options.
多种主要癌症类型在发病率和生存率方面表现出显著的性别差异。性别作为生物学因素是否以及如何影响肿瘤发生、进展和生存值得深入研究，因为这类知识可能催生新颖、精准的预防和治疗策略。我们综述了食管癌、膀胱癌、头颈癌、肺癌、肝癌、肾癌、胃癌和皮肤黑色素瘤中性别差异的流行病学和分子数据，以及雄激素和雄激素受体（AR）活性在这些癌症中的潜在作用。文中简要讨论了潜在的分子机制。睾酮（T）水平升高似乎与肝癌和皮肤黑色素瘤发病率增加相关，而与食管癌风险降低相关。在肿瘤发生和进展过程中，AR活性并不总是与T水平相关。较高的AR表达与食管鳞状细胞癌较差的生存率相关，而AR在头颈鳞状细胞癌和黑色素瘤患者生存中的作用则不一致。AR在肝癌、肾癌、黑色素瘤和肺癌中的分子影响存在争议。然而，AR很可能促进食管癌、膀胱癌、头颈癌和胃癌的肿瘤生长和/或进展，因此与较差的生存率相关。被诊断为后一组肿瘤的患者可能从靶向AR的治疗方法中获益。总体而言，关于性激素雄激素和AR在这些癌症中的研究有限。需要进一步研究以确定T与癌症风险之间可能存在的U型关系，并阐明睾酮和AR在其中一些肿瘤中的作用，以促进我们对性别差异的理解，并探索基于T/AR的新型治疗方案。
肿瘤(癌症)患者之家