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Regulation Of Gene Expression » Regulation Of Prokaryotic Gene Expression

Major Discovery: How Carcinogens Cause Cancer

Hunting for Genetic Mutations and Cancer
A little background:


1. What is a gene? A gene is an assembly line that produces a protein. A gene is made out of DNA.
2. What are proteins? Proteins are the major building blocks of cells.
3. What is a mutated gene? A mutated gene is a modified assembly line. A modification can take many forms, such as removing an essential part of the assembly line, replacing an important part with junk, etc. Very rarely a mutation is beneficial to the organism (X-Men, Evolution, Lance Armstrong?). In all other cases, a mutated gene is considered damaged DNA.


Current belief:


What is the cause of cancer? The word cause has two meanings. The first refers to the elements in the environment which impact our body, for instance, tobacco, x-ray radiation, asbestos, other chemicals, etc. These elements are usually called carcinogens. Today, hundreds of substances and mixtures are classified as carcinogens. The other meaning of the word cause refers to the internal element of the body which is the first to collapse under the attack of the carcinogens. Let us call this element our "Achilles heel."


The current belief in medical research holds that most cancers are caused by exposure to carcinogens, and that carcinogens cause cancer by mutating genes. In other words, according to the current belief, the structural integrity of our genes is our Achilles heel, and therefore, the first internal element to collapse under the attack of the carcinogens. This belief is so ingrained that the National Human Genome Research Institute (NHGRI), an institute at the NIH, recently stated that "all cancers are based on genetic mutations in body cells." Moreover, a search on PubMed, the search engine for scientific papers in life science, with the keywords "Mutation" AND "cancer" produced 86,490 papers and 12,238 reviews. Mutation hunting is also a big business. Look at the NIH budget allocated to discoveries of genetic mutations, the number of biotech companies chasing genetic mutations, the magnitude of the licensing agreements between biotech and pharmaceutical companies aimed to utilize newly discovered genetic mutations, and the number of stories in the media on genetic mutations and their so-called "link" to disease. However, this huge effort and billions of dollars has produced few discoveries and little benefits to the public. The reason for this limited success is simple. The cause of most cancers is not a genetic mutation. Our Achilles heel is not the structural integrity of our genes.


The story of the BRCA1 gene is a typical example of mutation hunting.


The Mystery of BRCA1
Genes, in general, produce proteins, which are the building blocks of cells. The concentration of proteins is tightly regulated. A mutated or physically altered gene produces an abnormal concentration of its protein, which may lead to disease. In 1994, Mark Skolnick, PhD, discovered the BRCA1 gene (BRCA1 is short for BReast CAncer 1). Following the discovery, scientists observed an abnormally low level of the BRCA1 protein in breast cancer tissues. The BRCA1 protein is a cell cycle suppressor, which means that the protein prevents cell replication. This observation created a lot of excitement. At the time, scientists believed that they were on the verge of finding the cause of breast cancer. The reasoning was that breast cancer patients must have a mutated BRCA1 gene, that is, a defected BRCA1 assembly line, which would explain the decreased production of the protein, and the excessive replication of breast cancer cells in tumors.


In the United States, 180,000 cases of breast cancer are diagnosed each year. However, the BRCA1 gene is mutated in less than 5% of these cases. In more than 95% of breast cancer patients the gene is not mutated, the assembly line is not defected.


So here is the mystery. If the gene is not mutated in the great majority of the breast cancer patients, why are the tumors showing low levels of the BRCA1 protein? Today, this is one of the biggest mysteries in cancer research.


The BRCA1 gene is not unique. Many normal (perfect shape, non-mutated) genes exhibit a mysterious abnormal (increased or decreased) production of proteins in cancer. Moreover, studies also report abnormal gene expression of normal genes in other diseases, such as atherosclerosis, obesity, osteoarthritis, type II diabetes, alopecia, type I diabetes, multiple sclerosis, asthma, lupus, thyroiditis, inflammatory bowel disease, rheumatoid arthritis, psoriasis, atopic dermatitis, and graft versus host disease.


According to Dr. Raxit J. Jariwalla in his European Journal of Cancer paper: (Jariwalla RJ. Microcompetition and the origin of cancer. Eur J Cancer. 2005 Jan;41(1):15-9): "The prevalent view of the nature of cancer holds that it is a complex genetic process resulting from the progressive accumulation of mutations in specific cellular genes, such as proto-oncogenes or tumor-suppressor genes, leading to perturbations in processes involving signal transduction, cell cycle regulation, and/or apoptosis. Genetic instability in tumors has been known for decades, however, the role of genomic instability in causing and promoting tumor growth remains controversial. Furthermore, although many studies report abnormal gene expression in cancer cells, often, no mutations or chemical modifications are observed around the locus of the dysregulated gene(s), suggesting that a genetic alteration is not the initiating event of cancer."


So what is the cause of most cancers, and how do carcinogens cause cancer? You can find the answer to these questions at http://www.causeofcancer.org/


John S. Boyd, Ph.D.
The Center for the Biology of Chronic Disease (see http://www.cbcd.net/), and causeofcancer.org (see http://www.causeofcancer.org/), Rochester, NY


We are a 501(c)3 not-for-profit organization that specializes in researching the biology of chronic disease. By "the biology of chronic disease" we mean the original disruption that causes the disease, and the sequence of events that lead from the original disruption to the development of clinical symptoms. We hope that once the biology is clear, pharmaceutical and biotech companies will be able to formulate drugs that reverse the effects of the disruption, and therefore cure the disease, or even block the original disruption, and therefore prevent the disease from developing in healthy individuals.


Source: www.ezinearticles.com