Association between polymorphisms in the leptin promoter and leptin receptor genes and cancer in a mediterranean population of the PREDIMED study

Background

Leptin is a hormone produced mainly by the adipose tissue and related in the regulation of food intake and energy balance. Elevated leptin levels and obesity has been shown to increase breast cancer risk in postmenopausal women. Our objective has been to estimate the risk of cancer arising from the common polymorphism within the 5' unstranslated region of the leptin gene (-2,548G/A) and Q223R polymorphisms in the LEPR gen, which has been associated with leptin levels, in a Mediterranean population.

Methods

The PREDIMED Study is a multi-center, randomized trial aimed at assessing the effects of the Mediterranean Diet on cardiovascular primary prevention. We analyzed 1108 participants (404 men and 704 women) high cardiovascular risk subjects (67 ± 6 years) were selected from a Spanish Mediterranean population. Demographic, clinical, biochemical, anthropometric, genetic and life-style variables were obtained.

Results

84 (7.6%) of the 1108 participants suffered from cancer after a median follow up of 4.8 years. The group of cancer patients showed 42.9% of current or former smokers versus 33.9% in the non cancer participants group (p = 0.003). Prevalence of the -2,548G/A genotypes were: 21.4% GG, 49.7% GA, 28.9% AA (allele frequencies, G = 0.463 and A = 0.537) and of the Q223R genotypes were: 13.6% QQ, 47.7% QR, 38.7% RR (allele frequencies, Q = 0.375 and R = 0.625). Interestingly, we found a consistent association of the SNP in the leptin gene with lower cancer risk. The lower risk of cancer associated with the A allele remained significant (OR = 2.21; 95% CI, 1.04-4.72) after adjustment for gender, age and tobacco smoking.

Conclusions

The allele A in the polymorphism -2,548G/A of the leptin gene is associated with lower cancer risk in this Mediterranean population.

Clinical trial identification

ISRCTN.org Identifier: ISRCTN35739639

Legal entity responsible for the study

Universitat de València

Funding

Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo

Disclosure

All authors have declared no conflicts of interest.