Department of Obstetrics and Gynecology, Women's Health Institute, Cleveland Clinic, Cleveland, Ohio.
Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
Endocrinology. 2018 Aug 1;159(8):3069-3080. doi: 10.1210/en.2018-00379.
It is well established that obesity increases the incidence and worsens the prognosis of women's cancer. For breast cancer, women with obesity exhibit more than a twofold increase in the odds of being diagnosed with cancer, with a greater risk of advanced stage at diagnosis, and ≤40% greater risk of recurrence and death than their normal-weight counterparts. These findings are similar in gynecologic cancers, where women who are obese with a body mass index (BMI) >40 kg/m2 have up to six times greater risk of developing endometrial cancer and a 9.2% increase in mortality with every 10% increase in BMI. Likewise, patients with obesity exhibit a twofold higher risk of premenopausal ovarian cancer, and patients who are obese with advanced stage ovarian cancer have shown a shorter time to recurrence and poorer overall survival. Obesity is accompanied by changes in expression of adipose factors that act on local tissues and systemically. Once obesity was recognized as a factor in cancer incidence and progression, the adipose cytokine (adipokine) leptin became the focus of intense investigation as a putative link, with nearly 3000 publications on the topic. Leptin has been shown to increase cell proliferation, inhibit apoptosis, promote angiogenesis, and increase therapeutic resistance. These characteristics are associated with a subset of cells in both liquid and solid tumors known as cancer stem cells (CSCs), or tumor initiating cells. We will review the literature discussing leptin's role in breast and gynecologic cancer, focusing on its role in CSCs, and consider goals for targeting future therapy in this arena to disrupt tumor initiation and progression in women's cancer.
肥胖症增加了女性癌症的发病率并降低了其预后，这一点已经得到充分证实。对于乳腺癌，肥胖女性患癌症的几率增加了两倍多，而且在诊断时更有可能处于晚期，复发和死亡的风险比正常体重的女性高 40%。在妇科癌症中也有类似的发现，体重指数（BMI）>40kg/m2 的肥胖女性患子宫内膜癌的风险增加了六倍以上，BMI 每增加 10%，死亡率就增加 9.2%。同样，肥胖症患者患绝经前卵巢癌的风险增加了两倍，而患有晚期卵巢癌的肥胖症患者复发时间更短，总体生存率更差。肥胖症伴随着脂肪因子表达的变化，这些因子作用于局部组织和全身。一旦肥胖被认为是癌症发病率和进展的一个因素，脂肪细胞因子（ adipokine ）瘦素就成为了一个潜在的关联的焦点，关于这个主题已经有近 3000 篇出版物。瘦素已被证明可增加细胞增殖、抑制细胞凋亡、促进血管生成并增加治疗耐药性。这些特征与液体和实体肿瘤中的一组细胞（称为癌症干细胞（CSC）或肿瘤起始细胞）有关。我们将回顾讨论瘦素在乳腺癌和妇科癌症中作用的文献，重点讨论其在 CSC 中的作用，并考虑在该领域靶向未来治疗的目标，以破坏女性癌症中的肿瘤起始和进展。
