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Unraveling the Genetic Secrets of Hereditary Diffuse Gastric Cancer: The Role of CDH1 and Beyond

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Ayanna Amadi
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Unraveling the Genetic Secrets of Hereditary Diffuse Gastric Cancer: The Role of CDH1 and Beyond

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Regarded as a significant global health burden, gastric cancer steals the lives of more than 7% of the global population who succumb to cancer each year. Of these cases, a distinct subset known as hereditary diffuse gastric cancer (HDGC) paints a chilling picture. Its pattern of familial clustering alludes to a deeper genetic mystery beneath the surface. As scientists unravel the secrets of HDGC, the role of the CDH1 gene has come to the fore, shedding light on potential avenues for prevention, treatment, and cure.

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The Genetic Basis of HDGC: The CDH1 Gene

The CDH1 gene is a crucial player in the story of HDGC. It encodes a protein that functions as a calcium dependent cell-cell adhesion glycoprotein. In layman's terms, CDH1 acts as the glue that binds cells together. However, when mutations in this gene occur, it disrupts this delicate balance, leading to uncontrolled cell growth and the progression of cancer. Such mutations contribute to the development of various cancers, including breast cancer, intestinal cancer, and most notably for our discussion, stomach cancer. The CDH1 gene is altered in over 3% of all cancers, with its status serving as an inclusion eligibility criterion in clinical trials for some types of cancer, including HDGC.

Further Complexity: CTNNA1 and MAP3K6

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As we delve deeper into the genetic landscape of HDGC, other genetic players such as CTNNA1 and MAP3K6 emerge. These genes also contribute to the development of HDGC, adding a layer of complexity to the genetic basis of this cancer. Further understanding of these genetic drivers could potentially open up new paths for targeted therapies.

The Life-Saving Option: Prophylactic Total Gastrectomy (PTG)

Despite the challenges associated with detecting HDGC and the complex genetic factors involved, there is a life-saving option for individuals with CDH1 mutations and a family history of HDGC: prophylactic total gastrectomy (PTG). This preventative surgical procedure involves the removal of the stomach before cancer has a chance to develop. In some cases, such as a reported case of a 24-year-old male with the CDH1 gene mutation, robotic surgery has been utilized for prophylactic gastrectomy, demonstrating the intersection of genetics and modern technology in the fight against HDGC.

The Ongoing Battle Against HDGC

As the scientific community continues to unravel the genetic mysteries of HDGC, the battle against this deadly cancer is far from over. The hope lies in continued research, unwavering dedication, and the potential for new preventative and curative avenues. With each new discovery, such as the role of CDH1 and other genetic factors, we move a step closer to rewriting the tragic narrative of HDGC with a triumphant chorus of prevention and cure.

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