肿瘤细胞治疗研究
英文原题：Obesity and Cancer: A Translational Science Review.
超重和肥胖与更高的癌症发病率相关，在美国每年占新发癌症诊断的10%。减重可能通过减轻肥胖的不良影响来降低癌症风险，但可能需要减重超过10%才能降低癌症风险。
肥胖与多种癌症风险增加相关，包括子宫内膜癌、食管癌、胃癌、肾癌、结直肠癌、肝癌、胆囊癌、胰腺癌、前列腺癌、绝经后乳腺癌、卵巢癌和甲状腺癌。在美国，超重和肥胖约占每年新发癌症诊断的10%，在子宫内膜癌和肝胆癌等某些癌症中占比高达50%。观察：超重定义为体重指数（BMI）25至29.9，肥胖定义为BMI 30或以上。肥胖和超重的特征是脂肪组织过度积累，破坏了其能量储存的主要功能。以游离脂肪酸形式存在的过剩能量被转移至正在发展的癌细胞，并通过氧化应激和DNA损伤导致的基因组不稳定性刺激癌症发展。脂肪组织功能障碍的其他定义性特征包括炎症和激素产生改变，如雌激素和瘦素增加、脂联素减少。炎症性脂肪组织与全身炎症介质升高相关，如前列腺素E2、细胞因子白细胞介素1β和白细胞介素6以及肿瘤坏死因子α。这些介质直接或间接促进肿瘤生长，途径包括刺激雌激素生物合成——这可促进乳腺癌、卵巢癌和子宫内膜癌等激素敏感性癌症的增殖——或通过髓源性抑制细胞的积累以及细胞毒性T细胞和NK 细胞数量和功能的减少，抑制免疫介导的对发展中的癌细胞的清除。炎症和氧化应激也由肥胖相关的肠道共生菌种（如 Akkermansia muciniphila）耗竭以及与临床前模型中癌症发展相关的细菌种群（如 Bilophila）过度增殖所激发。在观察性研究中，通过减重手术（n = 30 318）或使用胰高血糖素样肽 1 受体激动剂（n = 1 651 452）减重超过 10% 的患者，肥胖相关癌症发病率有适度降低（绝对变化，-0.02% 至 -0.5%）。
IMPORTANCE: Obesity is associated with increased risk of cancer, including endometrial, esophageal, gastric, kidney, colorectal, liver, gallbladder, pancreas, prostate, postmenopausal breast, ovarian, and thyroid cancers. Overweight and obesity account for approximately 10% of new cancer diagnoses annually in the US and up to 50% of certain cancers such as endometrial and hepatobiliary cancer. OBSERVATIONS: Overweight is defined as body mass index (BMI) of 25 to 29.9 and obesity as BMI of 30 or greater. Obesity and overweight are characterized by excess accumulation of adipose tissue, which disrupts its primary function of energy storage. Excess energy, in the form of free fatty acids, is transferred to developing cancer cells and stimulates cancer development through genomic instability caused by oxidative stress and DNA damage. Other defining features of adipose tissue dysfunction include inflammation and altered hormone production such as increased estrogens and leptin and decreased adiponectin. Inflamed adipose tissue is associated with systemic elevations in inflammatory mediators, such as prostaglandin E2, the cytokines interleukin 1β and interleukin 6, and tumor necrosis factor α. These mediators promote tumor growth directly or indirectly by stimulating estrogen biosynthesis, which can promote proliferation of hormone-sensitive cancers such as breast, ovarian, and endometrial cancer, or by suppressing immune-mediated elimination of developing cancer cells through accumulation of myeloid-derived suppressor cells and reductions in the amount and function of cytotoxic T cells and natural killer cells. Inflammation and oxidative stress are also stimulated by obesity-associated depletion of gut commensal bacteria species (eg, Akkermansia muciniphila) and overgrowth of bacterial populations associated with cancer development in preclinical models (eg, Bilophila). In observational studies, patients who lost more than 10% of body weight through bariatric procedures (n = 30 318) or with glucagon-like peptide 1 receptor agonists (n = 1 651 452) had modest reductions in obesity-associated cancer incidence (absolute change, -0.02% to -0.5%). CONCLUSIONS AND RELEVANCE: Overweight and obesity are associated with higher rates of cancer and account for 10% of new cancer diagnoses annually in the US. Weight loss may reduce cancer risk by attenuating adverse effects of obesity, but greater than 10% weight loss may be necessary to reduce cancer risk.
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