Hypercoagulation Screening as Marker of Occult Cancer in a Population of Healthy Blood Donors: The Hypercan Prospective Study
Authors: Falanga Anna , Marchetti Marina , Gamba Sara , Russo Laura , Tartari Carmen Julia , Giaccherini Cinzia , Verzeroli Cristina , Piras Francesca , Milesi Viola , Vignoli Alfonso , Brevi Shenaz , Rio Francesca , Barcella Luca , Sampietro Giuseppe 
Published: October 2019

Abstract
INTRODUCTION and AIM: The HYPERCAN study is an ongoing prospective Italian multicenter trial, designed to test whether the persistence of a laboratory hypercoagulation abnormalities may predict early cancer diagnosis in healthy subjects (Project A), or prognosis and response to therapy in patients with cancer (Project B). The aim of this abstract is to present a preliminary analysis of data collected for project A.
MATERIAL AND METHODS: A large healthy population of Italian blood donors from Bergamo and Milan areas (North Italy) is prospectively enrolled after informed written consent and followed-up for 5 years for the occurrence of cancer. As established by a monitoring schedule, blood donors are periodically screened for a series of serological, biochemical and clinical parameters, and tested for viral infections. We plan to enroll 10,000 donors of both gender, age range 35-65, in 5 years. Blood samples from each study subject are collected at enrollment and after 8-10 months, and processed to obtain plasma, buffy coat, and serum subsamples, which are stored in a dedicated biobank until testing for hypercoagulation biomarkers. Demographic and clinical data are collected, including age, gender, body mass index (BMI), current medications, relevant comorbidities, routine hematological and biochemical workup. In addition, subjects are asked to fill in a questionnaire on lifestyle, smoke and dietary habits. An identification of all malignant tumors, according to the categories 140-208 (International Classification of Diseases) is carried out every 6 months.
RESULTS: Between April 2012 and June 2016, 6,607 blood donors (70% males; median age 48 years) have been recruited. Routine biochemical and hematological workups are into the normal range values in more than 90% of subjects. The analysis of questionnaires reveals that 57% of the donors were not smokers, 15% regular smokers, 28% ex-smokers; 49% of them were moderate/low alcohol consumer (≥ 2 drink/die). The crude incidence of all malignant cancers in the Bergamo/Milan area is 552 cases/100,000 persons/year in males and 382 cases/100,000 person/year in females. According to the Cancer Registry, 57 cancer cases (38 males and 19 females) are to be expected in the general population in the age range 35-65 years, after a median follow-up of 2.5 years. In our population, at June 2016, after a median follow-up of 2.5 years, we recorded a total of 46 cancer cases (35 M / 11 F). Five cases were excluded because diagnosis occurred within 6 months from enrollment (incident cancer cases); the remaining 41 cases included in the analysis were diagnosed with cancer 6-28 months from enrollment (median time to diagnosis = 24.8 months). Median age at diagnosis of cancer was 53 years. The most frequent tumor type in male donors was prostate cancer (25.8%), followed by colo-rectal (19.3%) and thyroid (12.9%) cancers. In female donors, breast cancer was the most frequent (40%). Currently, the enrollment of healthy donors and follow-up is ongoing, as well as the identification of new cancer cases. Next, according to the original plan, samples from 3 matched cancer-free donors for each cancer-case donor (cancer: non-cancer = 1:3 ratio) will be analyzed in parallel for hypercoagulation markers.
CONCLUSIONS: This preliminary analysis reveals that the distribution of tumor types in our population reflects the same as reported for the general population of the same geographic area. Second, in our population of healthy blood donors, the incidence of cancer diagnosis is lower than that predicted from epidemiological data. This message supports the concept that a healthy lifestyle can be effective to prevent cancer.
Project funded by AIRC "5xMILLE" n. 12237 grant from the "Italian Association for Cancer Research (AIRC)".

Disclosures
Falanga: Pfizer: Speakers Bureau; Aspen: Speakers Bureau; Janssen: Speakers Bureau.