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Effect of Genetic Variability within 8q24 on Aggressiveness Patterns at Diagnosis and Familial Status of Prostate Cancer

Authors' Affiliations: ¹ CeRePP, Tenon Hospital; ² Assistance Publique-Hôpitaux de Paris, Departments of Urology and Pathology, Tenon and Pitie-Salpetriere Hospitals, GHU Est, University Paris VI, Paris, France; ³ Department of Urology, CHU d'Angers, Angers, France; ⁴ Department of Urology, CHU Brabois, Nancy, France; ⁵ Department of Urology, Hopital de la Cavale Blanche, Brest, France; ⁶ Bayesia SA, Laval, France; and ⁷ Department of Pathology, Hopital de la Miletrie, Poitiers, France

Requests for reprints: Olivier Cussenot, Hôpital TENON, Service d'Urologie-Batiment Gabriel, 4 rue de la Chine, 75020 Paris, France. Phone: 33-1-56-01-64-95; Fax: 33-1-56-01-76-47; E-mail: olivier.cussenot{at}tnn.aphp.fr.

Purpose: Recently, two independent loci located at 8q24 that contribute to prostate cancer risk in men of European origin were identified.

Experimental Design: Using Bayesian probability network and logistic regression model, we searched for associations between 34 single-nucleotide polymorphisms (SNP) located at 8q24 and the aggressiveness patterns of prostate adenocarcinoma or familial history of cancers in 823 White Caucasian French men.

Results: Probability network according to the Markov chain algorithm separated the SNPs into two main groups: The first one was linked to the locus marked by rs6983267 and the second one was linked to the locus marked by rs1447295. When the patients were stratified according to tumor stage and prostate-specific antigen value, the association between the variant genotypes from six SNPs located in the second network and prostate cancer risk was strongest or confined to the patients from the more aggressive classes. However, the association between prostate cancer risk and the CC genotype of rs7841264, which marked the recombination hotspot at 8q24, was confined to patients with the highest Gleason score (odds ratio, 2.15; 95% confidence interval, 1.27-3.64; P = 0.004). Interestingly, the G allele of rs6983267 was associated with familial prostate cancer risk.

Conclusions: Our data further support that variability at 8q24 is associated with a high risk of aggressive prostate cancer at diagnosis and is linked with familial history of prostate cancer. These results corroborate that 8q24 SNPs must be evaluated in terms of prostate cancer aggressiveness markers to optimize early diagnosis procedures and management of the disease.