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Region 2 of 8q24 is associated with the risk of aggressive prostate cancer in Caribbean men of African descent from Guadeloupe （French West Indies）

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Asian Journal of Andrology 2015年第1期17卷 117-119,I0010页

作者： geraldine cancel-tassin Marc Romana Cecile Gaffory Pascal Blanchet Olivier Cussenot Luc Multigner CeRePP Pitie-Salpetriere Hospital Paris 75013 France ER2 UPMC Univ Paris 6 Paris 75020 France 3U665 Inserm Pointe a Pitre 97159 Guadeloupe French West Indies Department of Urology Assistance Publique Hopitaux de Paris Tenon Hospital GHU Est Paris 75020 France U1085 - IRSET Inserm Pointe Pitre 97154 Guadeloupe French West Indies Department of Urology CHU Pointe--Pitre/Abymes Pointe Pitre 97159 Guadeloupe French West Indies.

Multiple regions of the genome have been associated with the risk of prostate cancer in Caucasians, particularly including several polymorphisms located at 8q24. Region 2 of 8q24 has been repeatedly found to be associated with the risk of prostate cancer among men of African descent, although one study performed in the Caribbean island of Jamaica did not report this finding. In this study, the single nucleotide polymorphism rs16901979, located in region 2 of 8q24, was genotyped in 498 cases of histologically confirmed prostate cancer and 541 controls from the French Caribbean islands of Guadeloupe, where the population is largely of African descent. The AA genotype and the A allele at rs16901979 were associated with elevated risks of prostate cancer （odds ratios [ORs] = 1.84, 95% confidence interval [95% CI] = 1.26-2.69, P= 0.002 and OR = 1.36, 95% CI = 1.13-1.64, P= 0.001, respectively）. Following stratification of the patients by disease aggressiveness, as defined by the Gleason score, the pooled genotypes AC ＋ AA were associated with a higher risk of a Gleasen score 〉7 at diagnosis （OR = 1.79, 95% CI = 1.17-2.73, P= 0.007）. In summary, the A allele at rs16901979 was associated with the risk of prostate cancer in the Caribbean population of Guadeloupe, confirming its involvement in populations of African descent. Moreover, our study provides the first evidence of an association between this variant and the risk of aggressive prostate cancer.

关键词： African Continental Ancestry Group aggressiveness Caribbean region genetic predisposition to disease prostaticneoplasms

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Quantitative proteomic determination of diethylstilbestrol action on prostate cancer

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Asian Journal of Andrology 2013年第3期15卷 413-420页

作者： Pierre Bigot Kevin Mouzat Muriel Bahut Nora Benhabiles geraldine cancel tassin Abdel-Rahmene Azzouzi Olivier Cussenot Department of Urology Angers University Hospital Angers 49933 France CeRePP Tenon Hospital Paris 75970 France Department of Biochemistry N'imes University Hospital NTmes 30029 France Plate-Forme Technologique de Biotechnologie Moleculaire Angers University Angers 49933 France 5CEA DSV IRCM SREIT Laboratoire de Cancerologie Experimentale Fontenay-aux-Roses 92265 France

Diethylstilbestrol （DES） has a direct cellular mechanism inhibition on prostate cancer. Its action is independent from the oestrogen receptors and is preserved after a first-line hormonal therapy. We aimed to identify proteins involved in the direct cellular inhibition effects of DES on prostate cancer. We used a clonogenic assay to establish the median lethal concentration of DES on 22RV1 cells. 22RV1 cells were exposed to standard and DES-enriched medium. After extraction, protein expression levels were obtained by two-dimensional differential in-gel electrophoresis （2D-DIGE） and isotope labelling tags for relative and absolute quantification （iTRAQ）. Proteins of interest were analysed by quantitative RT-PCR and western blotting. The differentially regulated proteins （P〈0.01） were interrogated against a global molecular network based on the ingenuity knowledge base. The 2D-DIGE analyses revealed DES-induced expression changes for 14 proteins （〉 1.3 fold; P〈0.05）. The iTRAQ analyses allowed the identification of 895 proteins. Among these proteins, 65 had a modified expression due to DES exposure （i.e., 23 overexpressed and 42 underexpressed）. Most of these proteins were implicated in apoptosis and redox processes and had a predicted mitochondrial expression. Additionally, ingenuity pathway analysis placed the OAT and HSBP1 genes at the centre of a highly significant network. RT-PCR confirmed the overexpression of OAT （P=0.006） and HSPB1 （P=0.046）.

关键词： cultured cells DES diethylstilbestrol ingenuity pathway analysis isotope labelling mass spectrometry prostate cancer proteomics

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