Genetic polymorphisms of RANTES, IL1-A, MCP-1 and TNF-A genes in patients with prostate cancer.
BACKGROUND
Inflammation has been implicated as an etiological factor in several human cancers, including prostate cancer. Allelic variants of the genes involved in inflammatory pathways are logical candidates as genetic determinants of prostate cancer risk. The purpose of this study was to investigate whether single nucleotide polymorphisms of genes that lead to increased levels of pro-inflammatory cytokines and chemokines are associated with an increased prostate cancer risk.


METHODS
A case-control study design was used to test the association between prostate cancer risk and the polymorphisms TNF-A-308 A/G (rs 1800629), RANTES-403 G/A (rs 2107538), IL1-A-889 C/T (rs 1800587) and MCP-1 2518 G/A (rs 1024611) in 296 patients diagnosed with prostate cancer and in 311 healthy controls from the same area.


RESULTS
Diagnosis of prostate cancer was significantly associated with TNF-A GA + AA genotype (OR, 1.61; 95% CI, 1.09-2.64) and RANTES GA + AA genotype (OR, 1.44; 95% CI, 1.09-2.38). A alleles in TNF-A and RANTES influenced prostate cancer susceptibility and acted independently of each other in these subjects. No epistatic effect was found for the combination of different polymorphisms studied. Finally, no overall association was found between prostate cancer risk and IL1-A or MCP-1 polymorphisms.


CONCLUSIONS
Our results and previously published findings on genes associated with innate immunity support the hypothesis that polymorphisms in proinflammatory genes may be important in prostate cancer development.
Sáenz-López
Pablo
P
Servicio de Análisis Clínicos e Inmunología, Hospital Universitario Virgen de las Nieves, Granada, Spain. pablosaenz-lopez@hotmail.com
Carretero
Rafael
R
Cózar
José Manuel
JM
Romero
José Maria
JM
Canton
Julia
J
Vilchez
José Ramón
JR
Tallada
Miguel
M
Garrido
Federico
F
Ruiz-Cabello
Francisco
F
D000368:Aged; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000235:genetics*; D018946:Chemokine CCL5 / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D053582:Interleukin-1alpha / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics*; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
C111835:CCL2 protein, human; C483024:CCL5 protein, human; D018932:Chemokine CCL2; D018946:Chemokine CCL5; C508584:IL1A protein, human; D053582:Interleukin-1alpha; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha