37P - Association of the rs4567312 variant in the leptin receptor gene with plasma leptin concentrations and lung cancer incidence in the PREDIMED study

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Cancer Aetiology, Epidemiology, Prevention
Lung and other Thoracic Tumours
Translational Research
Presenter Judith Begona Ramirez Sabio
Citation Annals of Oncology (2017) 28 (suppl_5): v1-v21. 10.1093/annonc/mdx361
Authors J.B. Ramirez Sabio1, J.V. Sorlí2, C. Ortega-Azorín2, P. Carrasco2, E.M. Asensio2, R. Barragán2, R. Fernández-Carrión2, C. Gallego2, J.I. González-Arráez2, J.A. Perez Fidalgo3, Ó. Coltell4, D. Corella2
  • 1Medical Oncology Unit, Hospital de Sagunt, 46520 - Pto. Sagunto/ES
  • 2Preventive Medicine And Ciber Fisiopatología De La Obesidad Y Nutrición, University of Valencia, 46010 - Valencia/ES
  • 3Medical Oncology, Hospital Clinico Universitario de Valencia, 46010 - Valencia/ES
  • 4Computer Languages And Systems. School Of Technology And Experimental Sciences, Jaume I University, Castellón/ES

Abstract

Background

Many studies have found leptin related genes involved in tumorigenesis and have suggested it may play a role in the pathogenesis of lung cancer. Leptin Receptor (LEPR) is expressed in many tissues and cells, including lung mucosal cells. LEPR was reported to be associated with tumor cell proliferation and angiogenesis. Our objective has been to estimate the association between the rs4567312-LEPR gene and lung cancer incidence in a Mediterranean population.

Methods

We analyzed 1094 participants (398 men, 696 women) recruited in the PREDIMED-Valencia Study. Participants were high cardiovascular risk subjects aged 67±6 years at baseline. PREDIMED is a multicenter randomized, controlled trial aimed at assessing the effect of the Mediterranean diet (MedDiet) on cardiovascular prevention (primary outcome). Cancer incidence was a secondary outcome in this trial. Demographic, clinical, life-style, biochemical, and genetic variables were obtained. Subjects were followed-up prospectively from 2003 to 2014 (in the extended-follow-up).

Results

We detected 12 new cases of lung cancer from 2003 to 2014 (1.1% cumulative incidence). Tobacco smoking was strongly associated with lung cancer incidence (91.7% of current or former smokers in lung cancer subjects vs 41.5% in the non-cancer participants (p = 0.001). In the whole population, prevalence of the rs4567312 polymorphism was: 95.5% CC, 4.4% CT and 0.1% TT. We also detected in the whole population an association between this polymorphism and plasma leptin concentrations, 26.9±22.9 ng/mL in CC vs 18.4±16.7 ng/mL in T carriers (p = 0.013). We found a strong association between the rs4567312-LEPR polymorphism and lung cancer risk, being higher in carriers of the T-allele. This association remained statistically significant (OR = 7.61; 95% CI: 1.74-33.37 for T-carriers vs CC) even after adjustment for gender, age, tobacco smoking, dietary intervention group (MedDiet vs control diet) and leptin levels.

Conclusions

T-carriers allele in the rs4567312-LEPR polymorphism presented a higher incidence of lung cancer in this Mediterranean population even after adjustment for tobacco smoking and dietary intervention.

Clinical trial identification

Controlled-trials.com number ISRCTN35739639

Legal entity responsible for the study

Instituto de Salud Carlos III and University of Valencia

Funding

Instituto de Salud Carlos III

Disclosure

All authors have declared no conflicts of interest.