Risk Model for Prostate Cancer Using Environmental and Genetic Factors in the Spanish Multi-Case- Control (MCC) Study

Prostate cancer (PCa) is the second most common cancer among men worldwide. Its etiology remains largely unknown compared to other common cancers. We have developed a risk stratification model combining environmental factors with family history and genetic susceptibility. 818 PCa cases and 1,006 healthy controls were compared. Subjects were interviewed on major lifestyle factors and family history. Fifty-six PCa susceptibility SNPs were genotyped. Risk models based on logistic regression were developed to combine environmental factors, family history and a genetic risk score. In the whole model, compared with subjects with low risk (reference category, decile 1), those carrying an intermediate risk (decile 5) had a 265% increase in PCa risk (OR = 3.65, 95% CI 2.26 to 5.91). The genetic risk score had an area under the ROC curve (AUROC) of 0.66 (95% CI 0.63 to 0.68). When adding the environmental score and family history to the genetic risk score, the AUROC increased by 0.05, reaching 0.71 (95% CI 0.69 to 0.74). Genetic susceptibility has a stronger risk value of the prediction that modifiable risk factors. While the added value of each SNP is small, the combination of 56 SNPs adds to the predictive ability of the risk model. Biological samples were stored at the biobanks supported by Instituto de Salud Carlos III- FEDER: Parc de Salut MAR Biobank (MARBiobanc) (), ‘Biobanco La Fe’ () and FISABIO Biobank (), as well as at the Public Health Laboratory of Gipuzkoa, the Basque Biobank, the ICOBIOBANC (sponsored by the Catalan Institute of Oncology), the IUOPA Biobank of the University of Oviedo, and the ISCIII Biobank. SNP genotyping services were provided by the Spanish ‘Centro Nacional de Genotipado’ (CEGEN-ISCIII). We thank all the subjects who participated in the study and all MCC-Spain collaborators. This work was supported by the ‘Acción Transversal del Cancer’, approved by the Spanish Ministry Council on the 11th October 2007, by the Instituto de Salud Carlos III, co-founded by FEDER funds –‘a way to build Europe’ (grants , , , , , , , , , , ,, , , , , , , , , and ). Support was also provided by the Fundación Marqués de Valdecilla (grant ); the Junta de Castilla y León (grant ); the Consejería de Salud of the Junta de Andalucía (); the Conselleria de Sanitat of the Generalitat Valenciana (grant ); the Recercaixa (grant ); the Regional Government of the Basque Country; the Consejería de Sanidad de la Región de Murcia; European Commission grants ; the Spanish Association Against Cancer (AECC) Scientific Foundation; the Catalan Government DURSI (grant ); the Fundación Caja de Ahorros de Asturias; the University of Oviedo; Societat Catalana de Digestologia; and COST action Eucolongene. The authors thank the “Bioinformatics and Research Group in Genetic and Environmental Epidemiology” (BRG-GEE) of the Cancer and Environmental Epidemiology Unit in III Institute of Health (ISCIII), Spain, for their technical scientific support (Group consisting of Pablo Fernández-Navarro (group leader), Mario González-Sánchez (bioinformatic), Javier González-Palacios (bioinformatic)). Sí