Stomach cancer is a significant global health burden, accounting for over 7% of cancer-related deaths annually. While only 1-3% of cases have a genetic basis, understanding these genetic drivers is crucial for developing preventative strategies.
Stomach cancer, a formidable foe in the global health arena, casts a long shadow on the lives of millions of people every year. Among its wide-reaching ramifications, a specific subgroup – hereditary diffuse stomach cancer (HDGC) – proves itself to be an especially aggressive and enigmatic adversary. Comprising about 10% of all stomach cancer cases, this group displays a startling pattern of familial clustering, indicating a deeper genetic tune playing beneath the surface.
Deciphering the secrets of HDGC has led scientists to a key player: the CDH1 gene. This gene, the blueprint for a protein called E-Cadherin, acts as a glue that holds cells together, forming the tight-knit communities that healthy tissue consists of.
Mutations in CDH1 disrupt this delicate dance, causing cells to lose their grip and embark on a journey of uncontrolled growth – the hallmark of cancer. Over 100 unique mutations in CDH1 have been identified, each representing a conflicting note in the symphony of a healthy genome. In about 40% of families affected by HDGC, these mutations act as conductors, guiding the tragic course of the disease.
However, the story of HDGC is not only etched into the pages of the CDH1 gene. Other actors such as CTNNA1 and MAP3K6 join the chorus, adding further complexity to the genetic landscape of this cancer. Like misplaced instruments, each gene mutation contributes to the disharmony that defines HDGC.
Understanding this complex interplay of genetic factors remains a central challenge, but holds great promise for unlocking new preventive and treatment options.
Despite the remaining secrets, a glimmer of hope shines through – prophylactic total gastrectomy (PTG). While this surgical intervention is drastic, it provides a life-saving option for individuals with a ticking time bomb of CDH1 mutations and a family history of HDGC. By removing the stomach, the potential breeding ground for cancer, PTG effectively silences the discordant melody and prevents the tragic symphony from playing out. Although PTG has its own challenges, it is the only definitive preventive measure currently available for these high-risk individuals.
The fight against HDGC is far from over. Deciphering the complexity of its genetic drivers, unraveling the supporting roles of other genes, and refining our understanding of the interplay between genetics and the environment are crucial steps in the battle. With continued research and unwavering commitment, we can hope to one day rewrite the script of HDGC and replace its tragic verses with a triumphant refrain of prevention and healing.
Erstes Krankenhaus der Universität Jilin
Mokhtari-Esbuie, F., et al. (2023). Bahnbrechender Einsatz der genetischen Analyse von CDH1 zur Identifizierung von Kandidaten für eine prophylaktische totale Gastrektomie zur Vorbeugung von erblich bedingtem diffusem Magenkrebs. eGastroenterologie. doi.org/10.1136/egastro-2023-100017.