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  • Type 1 plasminogen activator inhibitor as a common risk factor for cancer and ischaemic vascular disease: the EPICOR study

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Epidemiology
Research
Type 1 plasminogen activator inhibitor as a common risk factor for cancer and ischaemic vascular disease: the EPICOR study
  1. Licia Iacoviello1,
  2. Claudia Agnoli2,
  3. Amalia De Curtis1,
  4. Augusto di Castelnuovo1,
  5. Maria Concetta Giurdanella3,
  6. Vittorio Krogh2,
  7. Amalia Mattiello4,
  8. Giuseppe Matullo5,6,
  9. Carlotta Sacerdote5,7,
  10. Rosario Tumino3,
  11. Paolo Vineis5,8,
  12. Giovanni de Gaetano1,
  13. Salvatore Panico4,
  14. Maria Benedetta Donati1
  1. 1Laboratory of Molecular and Nutritional Epidemiology, Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo Neuromed, Pozzilli, Italy
  2. 2Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
  3. 3Cancer Registry, Ragusa, Italy
  4. 4Dipartimento di Medicina Clinica e Chirurgia, University of Naples “Federico II”, Napoli, Italy
  5. 5Human Genetics Foundation, HuGeF, Torino, Italy
  6. 6Department of Medical Sciences, University of Torino, Torino, Italy
  7. 7Department of Cancer Epidemiology, CPO-Piemonte, Torino, Italy
  8. 8Department of Epidemiology & Biostatistics, Faculty of Medicine, School of Public Health, Imperial College, London, UK
  1. Correspondence to Professor Licia Iacoviello; licia.iacoviello{at}neuromed.it

Abstract

Objectives We examined the association of plasminogen activator inhibitor-1 (PAI-1) levels with colorectal cancer, breast cancer, acute coronary syndrome (ACS) and ischaemic stroke.

Design Nested case-cohort study.

Setting The European Prospective Investigation into Cancer and Nutrition-Italy cohort.

Participants A centre-stratified random sample of 850 participants (286 men, 564 women) was selected as subcohort and compared with 303 colorectal cancers, 617 breast cancers, 688 ACS and 158 ischaemic strokes, in a mean follow-up of 9.11 years.

Main outcomes and measures Primary incident cases of colon cancer, breast cancer, ACS and ischaemic stroke. PAI-1 levels were measured in citrated plasma by ELISA. HR and 95% CI, adjusted by relevant confounders and stratified by centre, were estimated by a Cox regression model using Prentice method.

Results Individuals in the highest compared with the lowest quartile of PAI-1 had significantly increased risk of colorectal cancer (RR=2.28; 95% CI 1.46 to 3.55; P for trend<0.0012), breast cancer (HR=1.70; 95% CI 1.21 to 2.39; p<0.0055), ACS (HR=2.57; 95% CI 1.75 to 3.77; p<0.001) and ischaemic stroke (HR=2.27; 95% CI 1.28 to 4.03; p<0.0017), after adjustment for sex and age. Additional adjustment for disease-specific confounders, insulin or other metabolic variables did not modify the associations. Risk of colon cancer was stronger for men and for whole and distal colon localisation. Risk for breast cancer was stronger in postmenopausal women.

Conclusions Our data provide the first evidence that elevated levels of PAI-1 are potential risk factors for colorectal and breast cancer and a common pathway for cancer and cardiovascular disease.

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/

https://doi.org/10.1136/bmjopen-2013-003725

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