Increased incidence of neoplasia of the digestive tract in men with persistent activation of the coagulant pathway.
BACKGROUND
Thrombin promotes angiogenesis and cell proliferation in cancer. Whether thrombin turnover influences cancer incidence is unknown.


OBJECTIVE
To explore the relation between the status of the coagulant pathway and cancer incidence by population survey.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Miller
G J
GJ
Medical Research Council Cardiovascular Group, Wolfson Institute of Preventive Medicine, Barts, UK. g.miller@qmul.ac.uk
Bauer
K A
KA
Howarth
D J
DJ
Cooper
J A
JA
Humphries
S E
SE
Rosenberg
R D
RD
D003029:Coagulants / Q000378:metabolism*; D004067:Digestive System Neoplasms / Q000150:complications* / Q000453:epidemiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005164:Factor IX / Q000096:biosynthesis; D005167:Factor VII / Q000096:biosynthesis; D005344:Fibrinopeptide A / Q000096:biosynthesis; D005500:Follow-Up Studies; D006487:Hemostasis; D006801:Humans; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011516:Prothrombin / Q000096:biosynthesis; D013917:Thrombin / Q000378:metabolism; D013997:Time Factors
D003029:Coagulants; D005344:Fibrinopeptide A; D005167:Factor VII; D011516:Prothrombin; D005164:Factor IX; D013917:Thrombin