TGFBR1 gene Increases Risk of Colon Cancer

Researchers have identified a genetic abnormality that makes a person about nine times more likely to develop colorectal cancer.

Researchers studied 242 people in central Ohio with colorectal cancer and 195 people who did not have the disease. The researchers found that people who had defective transforming growth factor beta receptor 1 (TGFBR1) genes were 8.7 times more likely to develop colorectal cancer than those who lacked the abnormality.

The TGFBR1 gene normally helps protect against cancer. People inherit two copies of this gene (one from their mother and one from their father), and they usually produce equal amounts of the RNA that is needed to make the TGFBR1 protein. But in some people, one of these two genes is less active than the other. According to the study, 10-21 percent of people with colorectal cancer and 1-3 percent of the general population have this genetic abnormality.

An estimated one million people develop colon cancer each year worldwide. It is the third-most-common cancer in the United States, with 149,000 new cases and 50,000 deaths from the disease expected this year.

Colon cancer is difficult to detect, particularly in the early stages of the disease, because it often does not cause symptoms. The authors of this study suggest that simple blood tests that look for the genetic mutation may help diagnose colon and rectal cancer early in the disease, when it is most treatable. 

However, the study results need to be confirmed in larger trials that include more diverse populations.

Comments

[wendy]

What are the implications of this study? It seems that these types of studies will pave the path to genetic testing and then gene therapy. These options scare me - partly because I am unfamiliar with them and their consequences + side effects. What are the options then? If I have this mutated gene - will I have to get gene therapy? Ayurveda - which translates to "the science of life" - teaches that cancer is more a product of lifestyle and diet than genetic makeup. When we do not provide ideal environments for our bodies, cancer develops. In this regard, I hope that studies of this nature that provide early detection can be used by Dietitians and Lifestyle counselors to help people understand they have a choice in treatment and prevention options.

[hoart]

Besides colon cancer, TGF beta 1 has been proved to be associated with Loeys-Dietz aortic aneurysm syndrome, an autosomal dominant genetic syndrome with characteristics that include orbital hypertelorism, cleft palate and aortic or arterial aneurysm of the arteries. In addition, TGFBR1 was once thought to link to an increased risk in prostate cancer. However, that was then proved to be a false hypothesis.

[Ann]

It is good that researchers found the gene that can cause colon cancer. Genetics is one risk factor. Others include age, Crohn’s disease, diabetes, radiation therapy for cancer, etc. It is recommend that people who are older than 50 get colonoscopies.

[ATAD]

I know that colorectal cancers have been a major public concern because it is the second-leading cause of cancer death in adult Americans. I think this new discovery will be able to enhance better preventative treatment and maybe eventually even a cure. However, altered genes trigger all forms of cancers, so I am not surprised that this is the cause of this form of cancer. I do find it quite interesting that TGFBR1 gene tests are currently not recommended, but I am sure that years down the road this test will be part of the clinical practice of routinely evaluating a patient’s risk for colon cancer.

[Lindsey]

Diet is another risk factor for colon cancer. A diet high in fat, especially from animal sources, may increase the risk of colorectal cancer. Poor food choices may result in a deficiency of nutrients, such as calcium, magnesium, pyridoxine (vitamin B6) and folic acid, and these nutrients may be helpful in reducing the risk of colorectal cancer.

Consuming moderate to heavy amounts of alcohol, such as more than one drink a day for women and two for men, may also increase the risk of developing colon cancer. This is particularly true if the individual has a close relative, such as a parent, child or sibling with cancer.

[Heidi]

I have read that probiotics, the beneficial bacteria that help maintain a healthy GI tract, may help reduce the recurrence of colorectal tumors in patients who have previously undergone surgery for colon cancer. Most probiotics come from food sources, especially cultured milk products. Studies have noted benefits with Lactobacillus casei specifically. Long-term consumption of probiotics is considered safe and well tolerated. Diarrhea may be a sign of too many probiotics.

[colleen]

This is very interesting, but there’s a lot of info that is not yet available. For instance, how many people with the gene do NOT develop colon cancer and why? I wonder how alternative therapies that have been studied for the prevention or treatment of colon cancer fit into this picture. Might probiotics or calcium, for example, modify the TGFBR1 gene in a way that it is not expressed and does not cause cancer?

[Raymond]

Certain studies show that having a diet with a large amount of red meats and low amounts of vegetables, fiber-containing foods and fish increases one’s risk for colon cancer also. In the future, if TGFBR1 screenings are to be done, those identified with this gene abnormality should be instructed to focus more on their diets, to decrease the consumption of red meats and increase their dietary intake of vegetables, dietary fiber and fish. However, at this point, as the author stated, further studies need to be done to verify if this potential link between TGFBR1 abnormality and colon cancer actually exists.

[Annie C.]

A study conducted at the Ohio State University shows that the gene variation that increases the risk of inherited cancer can also arise during the development of spontaneous, or non-inherited, tumors. TGFBR1 6A is the variant that increases the risk of breast, colon and ovarian cancers. It is generally carried by nearly one in seven Americans and by one in six people with cancer. It can also arise as a gene mutation during cancer development. This enhances tumor growth and spread. The 6A variant was found in half of the metastatic liver tumors the researchers at OSU examined. The liver metastases had acquired the variant as a mutation during cancer progression.

[Neil]

For colon cancer, chemotherapy is started when there is metastasis to the lymph nodes. This is also considered stage III. A commonly used combination of chemotherapy for colon cancer is called FOLFOX- which stands for 5-fluorouriacil (aka 5-FU), leucovorin (aka folinic acid), and oxaliplatin. Folinic acid is used in this case, not as a rescue agent, but more to intensify the effects of 5-FU. Bevacizumab is also added to help prevent the spread of the cancer. The mechanism of action of bevacizumab is to prevent capillary growth of tumors, therefore, preventing the transport of nutrients to the tumor site, leading to retardation of tumor growth.

[oliver m.]

The advances of genetic testing and discovery of genetic abnormalities are a bit intimidating. Knowledge is power, but what you don’t know can’t hurt you. I can’t help but think of the potential this knowledge could impact if standard testing for numerous abnormalities conducted prenatally becomes more popular and widespread. Would future parents more likely consider aborting the fetus with the thought that they do not want to bring a baby that has difficulties into the world? Will those known to have the mutations be afraid to reproduce in fear of their offspring also obtaining the gene? Maybe it’s just my paranoia talking, but one never knows!

[naomi]

Current studies provide limited support that the presence of the gene TGFBR1 increases the risk of colon cancer. Even though family history is an important risk factor for colon cancer, the majority of colon cancers (about 80%) occur without a family history. Therefore, further research needs to be done in order to solidify this claim.

[Jean S.]

In the way that some of us have predispositions to developing allergies, others will be genetically predisposed to some form of cancer. On the other hand, it is important that we not see these markers as the actual disease. There has to be some mental balance maintained between what can happen and what has not yet happened - because it may not happen at all. That is my concern. None of us needs to grow up believing that we will get a particular cancer or that we will get cancer at all. That kind of negative expectation can create all kinds of havoc in the way we lead our lives.

On the other hand, knowing that we could be vulnerable can give us a leg up on preventative health precautions such as monitoring and creating as stress free a life as possible. I know people with allergies who seem to be immune to them at certain times of their lives, but when they are under a significant degree of stress, they experience their allergies in the worst way. We may not be able to control our genetic inheritance, but we do have a choice in how we learn to cope with the challenges in life and how that response will affect our health.

[Lester G.]

I applaud all the gene therapy research relating to all the cancers. These markers are valuable clues that we need to have as we negotiate our lives. However, I begin to foresee a time when after the birth of each child, the parents will be handed their swaddled baby and a printout of possible genetic connections to the world’s diseases. Welcome to the world, and "watch out!" Where is the line to be drawn between the value of this interior, invisible information and an intrusion into the private life of the individual. It was not that long ago when a dictator could decide the right to life based on a person’s religious affiliation, sexual preference and disabilities. The negative implication of some of the truly virtuous research ongoing today is not to be ignored. Protection of such private information must be guaranteed and the process of creating a secure system needs to precede all the resulting information.

[Pete]

This is great! This means that this genetic abnormality can be known at birth. The people with this genetic abnormality can be routinely examined for the development of rectal cancer. If this cancer can be caught early, many lives will be saved. I wonder how close they are to finding genetic abnormalities for pancreatic cancer. Pancreatic cancer is hardly ever found in stage 1 and definitely needs a marker to give people a heads up. Not that much funding is provided to pancreatic cancer since its victims usually pass away within six months.

[G.P.]

Gene testing and therapy is the future of cancer research and treatment. While this study needs to be confirmed in a larger population, the implications of the knowledge that mutation of TGFBR1 can increase the risk of colon cancer are huge.

One must keep in mind that many cases of cancer are not genetic. With the breast cancer mutation gene BRCA1 and BRCA2, only a fraction of the cases in the 10,000 to 20,000 women with inherited breast cancer (of an estimated 212,900 cases of breast cancer in 2005) expressed the BRCA mutation. Those that have two or more first-degree relatives who have had breast or ovarian cancer should consider genetic testing. It is possible that one day these same recommendations could be made regarding colon cancer.

[Ree]

Many of you bring up a good point about the implications of lifestyles as possible factors. Gene identification is a good tool, but people with poor diets and who rarely exercise are equally at risk. Let’s not forget that there are screening tests, such as a colonoscopy, which is recommended once every 10 years, starting age 50. It may not be as comfortable, but it’s a lot less expensive and is often covered by insurance. This way, we won’t have the political impact of genetic testing at our rears!

[Sam]

I agree with Ree in that targeting this gene in future diagnostic tests is a good idea, but that routine tests like a colonoscopy should still be done. The TGFBR1 genetic abnormality was present only in 10-21 percent of people with colon cancer, so this just goes to show that genes are only one part of the diagnosis and onset of these diseases.

[Mary]

I know a few people, including one of my family members, who found they had cancer in its late stages and couldn't really do much to fight it off. Detecting gene abnormalities seems like a great tool to help in detecting cancer early and providing more treatment options for patients.

[kay kelley]

It would be great if these results were validated with another study in a different area in the United States and with a diverse population. The results in this study are based on the population in just one area: central Ohio. It is quite possible that environmental toxins also played a role in these results. Having a way to identify an early stage of colon cancer would be terrific!

[liz]

I share Lester’s concern. What kind of implication could it have on the healthcare system? Insurers and prospective employers could use it against those who have the gene abnormality. Although having the defective gene would put one at a higher risk, it does not necessarily mean one will definitely develop cancer. I am all for it if it is going to be used for early detection as well as a preventative treatment.