Increasing efforts are being dedicated towards improving cancer care via personalized medicine. These efforts depend to a large degree on the availability of a knowledge foundation. Unfortunately, existing knowledge linking cancer drugs and potential efficacy biomarkers is in its infancy; and where links are known, they are frequently unstructured and poorly documented. We have developed a new open-access knowledgebase for precision cancer medicine (the PCM Wiki and Knowledgebase). This knowledgebase was constructed using an innovative, two-pronged approach involving a structured knowledgebase at the back-end, and an intuitive knowledge-sharing interface and user-friendly query engine in front. The knowledgebase was seeded with several patient case reports and information was mined via text-mining and literature review by human curators. Using our novel Wiki-based platform to present and share knowledge stored in the PCM knowledgebase, users are able to suggest corrections, propose additions or point to errors in the knowledgebase. The result is a community-driven evolving knowledgebase holding integrated and consolidated knowledge of markers and indications for personalized cancer medicine. We suggest that the PCM Knowledgebase and Wiki could serve as an important tool for the advancement of clinical trials and care in the field of precision cancer medicine.

We hypothesized that variants in genes expressed as a consequence of interactions between ovarian cancer cells and the host micro-environment could contribute to cancer susceptibility. We therefore used a two-stage approach to evaluate common single nucleotide polymorphisms (SNPs) in 173 genes involved in stromal epithelial interactions in the Ovarian Cancer Association Consortium (OCAC). In the discovery stage, cases with epithelial ovarian cancer (n = 675) and controls (n = 1,162) were genotyped at 1,536 SNPs using an Illumina GoldenGate assay. Based on Positive Predictive Value estimates, three SNPs-PODXL rs1013368, ITGA6 rs13027811, and MMP3 rs522616-were selected for replication using TaqMan genotyping in up to 3,059 serous invasive cases and 8,905 controls from 16 OCAC case-control studies. An additional 18 SNPs with P(per-allele)<0.05 in the discovery stage were selected for replication in a subset of five OCAC studies (n = 1,233 serous invasive cases; n = 3,364 controls). The discovery stage associations in PODXL, ITGA6, and MMP3 were attenuated in the larger replication set (adj. P(per-allele)>= 0.5). However genotypes at TERT rs7726159 were associated with ovarian cancer risk in the smaller, five-study replication study (P(per-allele)=0.03). Combined analysis of the discovery and replication sets for this TERT SNP showed an increased risk of serous ovarian cancer among non-Hispanic whites [adj. OR(per-allele) 1.14 (1.04-1.24) p = 0.003]. Our study adds to the growing evidence that, like the 8q24 locus, the telomerase reverse transcriptase locus at 5p15.33, is a general cancer susceptibility locus.