Miller G J, Bauer K A, Howarth D J, Cooper J A, Humphries S E, Rosenberg R D
Medical Research Council Cardiovascular Group, Wolfson Institute of Preventive Medicine, Barts, UK.
J Thromb Haemost. 2004 Dec;2(12):2107-14. doi: 10.1111/j.1538-7836.2004.01011.x.
Thrombin promotes angiogenesis and cell proliferation in cancer. Whether thrombin turnover influences cancer incidence is unknown.
To explore the relation between the status of the coagulant pathway and cancer incidence by population survey.
Of 4,009 middle-aged men clinically free of malignancy, 3052 (76.1%) were recruited. Measurements of hemostatic status were made annually for 4 years, and follow-up for morbidity and mortality was maintained thereafter. Persistent activation of the coagulant pathway was diagnosed when prothrombin fragment 1+2 and fibrinopeptide A concentrations exceeded the upper quartiles of the population distribution in two consecutive annual examinations. Cancer incidence rates in men developing persistent activation (taking the time of onset of activation as baseline) were compared with those in men remaining free of this condition.
Persistent activation of the hemostatic pathway was a distinct entity found in 111 men [43 expected by chance alone (P <0.001)], and associated with activation throughout the coagulation pathway. Total mortality (/1000 person-years) was higher in those with persistent activation than in others (17.1 and 9.7, respectively, P=0.015), owing to a higher mortality from all cancers (11.3 and 5.1, respectively, P=0.01), due in turn largely to a higher mortality from cancers of the digestive tract (6.3 and 1.9, respectively, P=0.004). Trends were similar for non-fatal cancers.
Persistent activation of the coagulant pathway plays a role in the preclinical phase of cancer and is associated with an increased incidence of clinical malignancy, especially of the digestive tract.
凝血酶可促进癌症中的血管生成和细胞增殖。凝血酶的周转是否影响癌症发病率尚不清楚。
通过人群调查探讨凝血途径状态与癌症发病率之间的关系。
在4009名临床上无恶性肿瘤的中年男性中，招募了3052名（76.1%）。连续4年每年测量止血状态，此后对发病率和死亡率进行随访。当凝血酶原片段1+2和纤维蛋白肽A浓度在连续两次年度检查中超过人群分布的上四分位数时，诊断为凝血途径持续激活。将发生持续激活的男性（以激活开始时间为基线）的癌症发病率与未出现这种情况的男性的癌症发病率进行比较。
止血途径的持续激活是在111名男性中发现的一种独特现象[仅偶然预期为43例（P<0.001）]，并与整个凝血途径的激活相关。持续激活者的总死亡率（/1000人年）高于其他人（分别为17.1和9.7，P=0.015），这是由于所有癌症的死亡率较高（分别为11.3和5.1，P=0.01），而这又主要归因于消化道癌症的死亡率较高（分别为6.3和1.9，P=0.004）。非致命性癌症的趋势相似。
凝血途径的持续激活在癌症的临床前期起作用，并与临床恶性肿瘤尤其是消化道恶性肿瘤的发病率增加有关。
