NCT Research

Program

Mission and Strategy

The Cancer Prevention, Control and Outcomes Program aims to use state-of-the-art methods and technologies to identify cancer risk factors and preventive strategies. Population-wide detection and screening programs develop preventive measures against cancer causes.

Cancer Prevention
 

Program researchers have made outstanding contributions to Primary Prevention by targeting infection-related cancers (Knebel-Doeberitz); by defining risk and preventive factors for a multitude of cancer types in the >500,000-person EPIC cohort, as well as multiple international consortia investigating genome-wide risk factors (Kaaks, Ulrich, Brenner, Chang-Claude, Risch); by establishing tobacco prevention activities (Thomas, Ferth); and by pursuing personalized prevention strategies with non-steroidal anti-inflammatory drugs (Ulrich). The new 200,000-person National Cohort, a Helmholtz project, will provide important insights into cancer etiology and prevention. In Secondary Prevention, which refers to early-detection strategies for precursor lesions or early cancers. Program researchers are leaders in early detection/screening of colorectal cancer and have translated basic science research on HPV and mismatch repair-deficient colorectal cancer into two phase I/II clinical trials of peptide-based HPV vaccines, as well as worldwide-used diagnostic tests (Knebel-Doeberitz). Tertiary Prevention encompasses treatment tailoring through prognostic markers and health behavior changes among cancer survivors to improve their clinical outcomes. Program researchers coordinate and participate in national and international consortia in tertiary prevention and pharmacogenetics for colorectal cancer (Ulrich, Brenner, Chang-Claude), in the NCI Cohort Consortium (Kaaks), and in the increasingly important area of physical activity/metabolic syndrome and cancer (Steindorf, Ulrich, Chang-Claude). Program Members also hold leadership positions in the German Consortia for Cancer Research and for Lung Research.

Achievements

We have demonstrated that familial risk of cancer affects not only young patients (Kharazmi BMJ 2012), that TERT promoter mutations are the most common feature of sporadic melanoma (Horn Science 2013, Fig. 6), that translocations may have a genetic origin (Weinhold Nature Genet 2013), and have defined four new genetic susceptibility loci for multiple myeloma (Chubb Nature Genet 2013). Program researchers have defined genome-wide changes in DNA methylation in breast and prostate cancer in preclinical rodent models and human samples and identified epigenetic changes as early diagnostic markers and as potential targets for cancer prevention (Faryna FASEB J 2012; Weischenfeldt Cancer Cell 2013). We have also developed a novel staining technique that makes it possible to unequivocally identify HPV-related lesions in tissue sections as well as in cytololgy samples, which is now used on a global scale (p16INK4a/Ki67 double staining technique; Reuschenbach Int J Cancer 2012; Ikenberg J Natl. Cancer Inst 2013). Based on the basic research of the Knebel group, two phase I/II clinical trials have been initiated to test peptide-based vaccines against (a) p16INK4a overexpressing HPV-related cancers and (b) frameshift peptides (FSPs) induced by deficient DNA mismatch repair in MSI-high cancers. With respect to colorectal cancer, the group has contributed significantly to the evaluation of effectiveness and cost-effectiveness of colonoscopy-based colorectal cancer early detection and prevention, appropriate screening intervals, and quality aspects of colorectal cancer screening (Brenner JNCI 2010; Brenner Ann Intern Med 2011/2012; Brenner J Clin Oncol 2011/2012; Brenner Gut 2011). We have identified a novel pre-malignant lesion in colorectal cancer patients affected by Lynch syndrome or hereditary non-polyposis colorectal cancer, and characterized immunological phenotypes and diagnostic approaches to characterize microsatellite-unstable colorectal cancers (Kloor Lancet Oncol 2012; Michel Int J Cancer 2010; Kloor J Clin Oncol 2011). We have demonstrated that use of aspirin or NSAID and genetic variability in prostaglandin synthesis is associated with risk and survival of colorectal neoplasia. Pharmacogenetic interactions exist for NSAID use, highlighting the potential for personalized prevention strategies based on inherited genetic characteristics. Proof of concept has been shown in a clinical trial (Coghill Gut 2011; Seufert Carcinogenesis 2013; Coghill Clin Canc Res 2011; Kraus Pharmacogen Genom 2013; Haug Genes Chrom Cancer 2012). We have helped identify and characterize lung, ovarian, breast, endometrial, pancreatic, and colorectal cancer risk loci as part of genome-wide association consortia (e.g., Gray-McGuire Cancer Res 2010; Peters Hum Genet 2012; Truong J Natl Cancer Inst 2010; Timofeeva Hum Mol Genet 2012; Pharaoh Nat Genet 2013; Bojesen Nat Genet 2013; Petersen Nat Genet 2010; Canzian Hum Mol Genet 2010; Campa JNCI 2011). Similarly, we have reported on hormonal, metabolic, and other biomarkers as key risk factors for multiple cancer types, including as part of the NCI-directed Cohort Consortium (Endog. Horm. & Br. Ca Coll. Group Lancet Oncology 2010/2013; Toniolo Cancer Res 2010; Grote Diabetologia 2011). Finally, we have shown that exercise intervention programs significantly reduce biomarkers of cancer risk both in plasma and directly in adipose tissue (Imayama Cancer Res 2012; Abbenhardt J Int Med 2013; Campbell Ca Prev Res 2013; Med Sci Sports Exerc 2010; J Appl Physiol 2010).

Pedigree of melanoma-prone family with TERT promoter mutations

Figure 6: Pedigree of melanoma-prone family with TERT promoter mutations (Horn Science 2013)

Goals

The Cancer Prevention, Control, and Outcomes Program leverages close interaction with NCT groups to pursue transdisciplinary and translational research. The program builds on existing and new study populations and unique biorepositories. Specific goals include:

  • Identification of genetic, behavioral, and environmental cancer risk factors to develop public health recommendations and tailored prevention strategies (e.g., Miller & Ulrich, Lancet 2013; Rudolph Cancer Res 2013; Horn Science 2013).
  • Development of biomarkers and diagnostic tests for cancer prevention and prognosis (e.g., Kloor Lancet Oncol 2012; Buck J Clin Oncol 2011).
  • Evaluation of physical activity, energy balance, and metabolic syndrome in prevention, prognosis, and treatment response (e.g., Wiskemann Blood 2010).
  • Development of new early-detection modalities for colorectal cancer, and evaluation of efficacy and cost-effectiveness (e.g., Brenner JNCI 2010).