Overexpressing leptin genetic polymorphism (-2548 G/A) is associated with susceptibility to prostate cancer and risk of advanced disease.
BACKGROUND
Leptin has been consistently associated with angiogenesis and tumoral growth. A G/A single nucleotide polymorphism (SNP) at the -2548 site in leptin gene (LEP) is associated with overexpression of leptin (A-allele).


METHODS
We evaluated DNA samples from 268 (536 alleles) unrelated individuals, 118 healthy controls (HCs) and 150 prostate cancer (PC) patients, for leptin gene (LEP) locus -2548 genotypes.


RESULTS
We found an overrepresentation of the A-allele in PC patients and that there is a significantly higher risk for PC among A carriers (OR = 1.60; confidence interval (CI), 1.13-2.28, P = 0.008). Linear trend analysis showed that quantitative increase of A-allele presence was associated with significantly higher risk for PC (P = 0.003) in heterozygous (OR = 2.11; CI, 1.20-3.71) and homozygous (OR = 2.93; CI, 1.27-6.75) genotypes. Furthermore, the AA and AG genotypes represent significantly higher risk (OR = 4.67; CI, 1.69-12.88 and OR = 2.58; CI, 1.19-5.58, respectively) for advanced disease.


CONCLUSIONS
According to our results we hypothesize that the polymorphism in LEP gene may be relevant to PC risk and progression, supporting the hypothesis for leptin involvement in cancer ethiopathogenesis.
Ribeiro
Ricardo
R
Molecular Oncology Unit, Instituto Português de Oncologia, Porto, Portugal.
Vasconcelos
André
A
Costa
Sandra
S
Pinto
Daniela
D
Morais
Antonio
A
Oliveira
Jorge
J
Lobo
Francisco
F
Lopes
Carlos
C
Medeiros
Rui
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D004273:DNA, Neoplasm / Q000032:analysis; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D020738:Leptin / Q000096:biosynthesis* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D018570:Risk Assessment
D004273:DNA, Neoplasm; D020738:Leptin