Oncogenetics

Determining whether a hereditary cancer predisposition is present, is important for both the cancer patient and his family. It is relevant for surveillance and prevention or early detection of new tumours, treatment options and issues surrounding the desire to have children. For this reason, it must be ensured that for every patient with cancer (now or in the past) referral for genetic testing is considered. In this article we indicate how to take a family history and where to find and how to apply referral criteria if such a question arises in clinical practice. The consequences of a genetic diagnosis are illustrated by a breast cancer case

Statin use is not associated with improved progression free survival in cetuximab treated KRAS mutant metastatic colorectal cancer patients: results from the CAIRO2 study.

Statins may inhibit the expression of the mutant KRAS phenotype by preventing the prenylation and thus the activation of the KRAS protein. This study was aimed at retrospectively evaluating the effect of statin use on outcome in KRAS mutant metastatic colorectal cancer patients (mCRC) treated with cetuximab. Treatment data were obtained from patients who were treated with capecitabine, oxaliplatin bevacizumab ± cetuximab in the phase III CAIRO2 study. A total of 529 patients were included in this study, of whom 78 patients were on statin therapy. In patients with a KRAS wild type tumor (n = 321) the median PFS was 10.3 vs. 11.4 months for non-users compared to statin users and in patients with a KRAS mutant tumor (n = 208) this was 7.6 vs. 6.2 months, respectively. The hazard ratio (HR) for PFS for statin users was 1.12 (95% confidence interval 0.78-1.61) and was not influenced by treatment arm, KRAS mutation status or the KRAS*statin interaction. Statin use adjusted for covariates was not associated with increased PFS (HR = 1.01, 95% confidence interval 0.71-1.54). In patients with a KRAS wild type tumor the median OS for non-users compared to statin users was 22.4 vs. 19.8 months and in the KRAS mutant tumor group the OS was 18.1 vs. 14.5 months. OS was significantly shorter in statin users versus non-users (HR = 1.54; 95% confidence interval 1.06-2.22). However, statin use, adjusted for covariates was not associated with increased OS (HR = 1.41, 95% confidence interval 0.95-2.10). In conclusion, the use of statins at time of diagnosis was not associated with an improved PFS in KRAS mutant mCRC patients treated with chemotherapy and bevacizumab plus cetuximab

Patient Characteristics.

<p>Patient Characteristics.</p

Kaplan-Meier plots for progression free survival for patients with KRAS wild type (19 statin-users and 145 nonusers) and KRAS mutant (16 statin-users and 83 nonusers) tumors treated with capecitabine, oxaliplatin, bevacizumab and cetuximab.

<p>Kaplan-Meier plots for progression free survival for patients with KRAS wild type (19 statin-users and 145 nonusers) and KRAS mutant (16 statin-users and 83 nonusers) tumors treated with capecitabine, oxaliplatin, bevacizumab and cetuximab.</p

Overview of the mevalonate pathway and the inhibition of HMG-CoA by statins.

<p><i>Mevalonate pathway causes prenylation of ras, N-glycosylation of EGFR and membrane and steroidsynthesis. Statins have inhibitory effects on the mevalonate pathway and thus on prenylation of k-ras. Abbreviations: Acetyl-CoA, Acetyl coenzyme A; EGFR, epidermal growth factor receptor; FTase, farnesyltransferase; GTase, geranylgeranyltransferase; HMG-CoA (reductase), 3-hydroxy-3-methyl-glutaryl-CoA reductase; -PP, -pyrophosphate.</i></p

Statin Use Is Not Associated with Improved Progression Free Survival in Cetuximab Treated KRAS Mutant Metastatic Colorectal Cancer Patients: Results from the CAIRO2 Study

Statins may inhibit the expression of the mutant KRAS phenotype by preventing the prenylation and thus the activation of the KRAS protein. This study was aimed at retrospectively evaluating the effect of statin use on outcome in KRAS mutant metastatic colorectal cancer patients (mCRC) treated with cetuximab. Treatment data were obtained from patients who were treated with capecitabine, oxaliplatin bevacizumab ± cetuximab in the phase III CAIRO2 study. A total of 529 patients were included in this study, of whom 78 patients were on statin therapy. In patients with a KRAS wild type tumor (n = 321) the median PFS was 10.3 vs. 11.4 months for non-users compared to statin users and in patients with a KRAS mutant tumor (n = 208) this was 7.6 vs. 6.2 months, respectively. The hazard ratio (HR) for PFS for statin users was 1.12 (95% confidence interval 0.78-1.61) and was not influenced by treatment arm, KRAS mutation status or the KRAS*statin interaction. Statin use adjusted for covariates was not associated with increased PFS (HR = 1.01, 95% confidence interval 0.71-1.54). In patients with a KRAS wild type tumor the median OS for non-users compared to statin users was 22.4 vs. 19.8 months and in the KRAS mutant tumor group the OS was 18.1 vs. 14.5 months. OS was significantly shorter in statin users versus non-users (HR = 1.54; 95% confidence interval 1.06-2.22). However, statin use, adjusted for covariates was not associated with increased OS (HR = 1.41, 95% confidence interval 0.95-2.10). In conclusion, the use of statins at time of diagnosis was not associated with an improved PFS in KRAS mutant mCRC patients treated with chemotherapy and bevacizumab plus cetuximab