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Gastric carcinoma

Clinical features and genetics

Sporadic or non-familial gastric carcinoma is the fourth most common form of cancer. In Germany alone, over 20,000 people develop gastric cancer each year. Sporadic gastric carcinoma occurs more frequently in older people, with a mean age of onset of 71 years in men and 76 years in women. In general, gastric cancer can be divided into two types. Intestinal type gastric carcinoma is the most common form. Here, the tumor tissue usually contains well-differentiated structures of the gastric mucosa. In contrast, diffuse type gastric carcinoma contains none of the structures of the gastric mucosa, and is characterized by infiltrative growth into the stomach tissue.

For both cancer types, the most important risk factor is infection with the bacterium Helicobacter pylori. A further key risk factor for gastric carcinoma is genetic load. The contribution of genetic factors to the development of sporadic gastric cancer is around 30%. Sporadic gastric cancer is a genetically complex disease that is characterized by the simultaneous presence of mutations or risk variants in multiple genes. These aggregates vary between individuals, and contribute to disease susceptibility via interacting effects. No specific risk genes for sporadic gastric cancer have yet been identified. However, their determination is crucial in terms of the development of novel treatment strategies.

Research concept

The goal of staR is to elucidate the cell biological causes of sporadic gastric cancer. Elucidation of disease-relevant processes could lead to the development of causal drug therapies. In addition, biomarkers could be developed to improve prevention for individuals who are at risk, and the assessment of prognosis for those affected. The decisive step in elucidating the cell biological causes lies in the identification of genetic risk variants.

In recent years, the elucidation of multifactorial disease has been facilitated by the introduction of the so-called genome-wide association study (GWAS) approach. We plan to use this molecular genetic method within staR. To date, no study has used the GWAS approach to investigate the causes of gastric cancer. Genetic association analyses are carried out in large cohorts of affected individuals and healthy controls in order to determine whether a specific allele of a genetic variant occurs more frequently in patients than in controls. If significant differences are apparent between the two groups, the allele that is overrepresented in the patient is considered to be the genetic risk factor. Association analyses can now be performed across the entire genome. The GWAS approach currently represents the state-of-the-art method for the elucidation of multifactorial disease. However, to identify disease-causing alleles with certainty, GWAS must be performed in relatively large case-control cohorts.

In the near future, Next Generation Sequencing (NGS) will become the state-of-the-art molecular genetic method for the analysis of multifactorial disease, and will allow complete sequencing (i.e., determination of the sequence of the bases) of the entire genome in large cohorts. NGS will enable the identification of risk variants for multifactorial diseases that cannot be identified via GWAS. Within the context of staR, NGS studies of sporadic gastric cancer will be performed at the earliest possible time-point.

Our research project does not end with the identification of risk genes, however. The detection of risk genes is a prerequisite for identifying pathways of relevance to sporadic gastric cancer via cell biological- and bioinformatic analyses.

Contact person

Prof. Dr. Johannes Schumacher

The staR website can be accessed under http://star-project.md/.

Selected Publications

Heinrichs SKM, Hess T, Becker J, Hamann L, Vashist YK, Butterbach K, Schmidt T, Alakus H, Krasniuk I, Höblinger A, Lingohr P, Ludwig M, Hagel AF, Schildberg CW, Veits L, Gyvyte U, Weise K,  Schüller V, Böhmer AC, Schröder J, Gehlen J, Kreuser N, Hofer S, Lang H, Lordick F, Malfertheiner P, Moehler M, Pech O, Vassos N, Rodermann E, Izbicki JR, Kruschewski M, Ott K, Schumann  RR, Vieth M, Mangold E, Gasenko E, Kupcinskas L, Brenner H, Grimminger P, Bujanda L, Sopeña F, Espinel J, Thomson C, Pérez-Aísa Á, Campo R, Geijo F, Collette D, Bruns C, Messerle K, Gockel I, Nöthen MM, Lippert H, Ridwelski K, Lanas A, Keller G, Knapp M, Leja M, Kupcinskas J, García-González MA, Venerito M, Schumacher J. Evidence for PTGER4, PSCA, and MBOAT7 as risk genes for gastric cancer on the genome and transcriptome level. Cancer Med. 2018 Oct;7(10):5057-5065.