Introduction
The cell is considered a bundle block of life. Similarly, cellular function and physiological function of the body are regulated by genes. Functions like metabolisms, enzymatic activity, and synthesis of biomolecules are regulated by genetic factors. These genetic activities are influenced by heredity and familial factors. Over the years, researchers have identified several genetic factors that are linked to gastrointestinal conditions. Not only diseases but also treatment outcomes is influenced by this.
What Is the Role of Genetic Testing in Colorectal Cancer?
Colorectal cancer is the third most prevalent cancer in the world. The number of deaths associated with colorectal cancer is the second highest in the world. Colorectal cancers are mainly of two types: colon cancer and cancer of the rectum. Colon cancer again can be of several types, like sigmoid colon cancer, ascending colon cancer, transverse colon cancer, descending colon cancer, and cancer of cecum.
Hereditary colon cancer cases can be categorized as polyposis and non-polyposis conditions. Several polyposis syndromes are associated with this, which are responsible for at least 1 percent of cases of colorectal cancers. Adenomatous polyposis syndrome is an autosomal dominant disorder. Patients suffering from this familial condition often complain of the presence of solid connective tissue tumors, gastric and duodenal polyps. APC gene, which acts as a tumor suppressor gene. Mutation of this gene in chromosome 5 is associated with colorectal cancer. In this condition, MYH base-excision repair gene mutation is seen. In some cases, mutation of the POLE or POLD1 gene can also be seen.
Lynch syndrome is another common disorder that is associated with colorectal carcinoma. This is known as hereditary non-polyposis colorectal cancer and is one of the commonest causes of colorectal cancer. This is also associated with an increased risk of cancer in other locations, such as the endometrium, ovary, biliary tract, stomach, and small intestine. This is also an autosomal variant condition. Mutation of genes like MLH1, MSH2, MSH6, or PMS2 or by an EPCAM is associated with this condition.
Juvenile polyposis syndrome is characterized by the presence of hamartomatous polyps in the gastrointestinal tract. This condition usually appears by the age of 20 with the presence of polyps in the colon, rectum, small intestine, and stomach. Variation in the genes such as SMAD4 or BMPR1A is associated with this condition.
What Is the Application of Genetic Testing to Inflammatory Bowel Disease?
Inflammatory bowel disease is a chronic inflammatory disease of the small intestine. This condition is usually caused by Crohn's disease (inflammatory disease of the bowel) or ulcerative colitis (inflammation of the colon and rectum). Abdominal pain, diarrhea, increased bowel movement, and abdominal bloating are the causative factors for this condition. Genetic alteration and homogeneous mutation of inflammatory receptors like IL (interleukin)-10 are associated with this condition. Though genetic alterations have minimal effect on this condition, such alterations may affect treatment procedures.
Azathioprine (AZA) is the key drug used in this disease. This drug helps to cure the inflammation of the gastrointestinal tract. This is also used as a steroid-sparing agent. As a result, the potentially harmful effect of steroids can be avoided. Thiopurine-S-methyltransferase (TPMT) is the primary liver enzyme that is useful in the digestion process of these drugs. Polymorphism of the gene present in chromosome 6 is associated with altered drug activity. As a result, decreased metabolism of Azathioprine causes the accumulation of metabolites like 6-mercaptopurine (6-MP). This has cytotoxic effects and causes suppression of the bone marrow. Apart from this, polymorphism of chromosome 20 is responsible for the altered functioning of the enzyme inosine triphosphate pyrophosphatase (ITPA). This enzyme is associated with the metabolism of Azathioprine. Decreased metabolism of Azathioprine leads to the accumulation of a substance known as 6-inosine triphosphate (ITP). Patients with such complications show symptoms of rash and flu-like symptoms. Apart from this, genetic alterations are also associated with decreased functioning of Infliximab.
What Is the Effect of Genetics On Pancreatic Cancer?
Pancreatic cancer is a relatively rare form of cancer with a high mortality rate. As these cancers arise from pancreatic duct cells, these cancers are known as pancreatic ductal carcinoma. Various risk factors like smoking, alcoholism, Helicobacter pylori infection, obesity, chronic pancreatitis, and cirrhosis of the liver are associated with this type of cancer. Genetic influence, in some cases, can also be observed.
Peutz–Jeghers syndrome is a condition in which gastrointestinal polyposis and mucocutaneous pigmentation can be seen. This condition most commonly affects the small intestine. Apart from this, the stomach, large intestine, and gallbladder are also affected by this condition. Mutation of the STK11 gene is responsible for this condition and pancreatic cancer.
Ataxia Telangiectasia is a rare condition that affects the nervous system and immunity. It is an autosomal recessive condition characterized by neurological dysfunctions, abnormal muscle movement, and muscle twitching. Mutation of ATM genes is associated with this condition. Several cancerous conditions like pancreatic cancer, leukemia, and lymphoma.
What Are the Effects of Genetics on Liver Diseases?
Metabolic liver diseases are one of the main causes of liver damage. Wilson’s disease is a major liver disorder characterized by the accumulation of excessive copper in the body. This condition is caused by defects in the ATP7B gene. Gilbert’s syndrome (disease of improper bile production) is another genetic condition that causes hyperbilirubinemia (high bilirubin level in the blood). Accumulation of the bile is caused by a genetic mutation of UGT1A1.
Cyclosporine and Tacrolimus are often prescribed to liver transplant patients to fight against any infections. Cytochrome P450 3A4 enzymes expressed from the liver and intestinal epithelial cells are responsible for the metabolism of these drugs. The gene known as CYP3A4, located in chromosome seven, is associated with the secretion of this enzyme. But in some cases, there are two variations that can be seen in this gene. This causes lower genetic transcription and lower drug levels. As a result, an increased amount of drugs is needed in such patients.
Conclusion
Genes regulate the physiologic action of biomolecules. Alteration in the genetic structure is known as mutation. This mutation is linked to several pathological conditions. Gastrointestinal cancers, polyps, liver disorders, and disorders of the bowel are related to abnormal genetic functioning. Also, genetic functioning influences the actions of several drugs. As a result, the treatment of several disorders is hampered. Thus, genetic analysis is importent for the successful treatment of gastrointestinal conditions.
