On pages 172-173, Dr. Moalem discusses the recent research that has linked methylation to cancer. The addition of methyl groups to DNA has been found to affect gene expression. This research a part of the study of epigenetics. Scientists have discovered that women with high methylation of the gene, PTX2, have a larger chance of breast cancer recurrence. Also, over many years, a habitual smoker gains massive build up of methyl around genes that naturally fight cancer. This is called hypermethylation. Longtime exposure to carcinogens can cause hypermethylation of genes that supress tumors, repair DNA, and detect cancer cells. Methylation of these genes stops gene expression and presents a person with high risk of getting cancer. This topic relates to big idea 3 because methylation of certain genes regulates their expression in an organism. Methylation of a gene to regulate gene expression is one of the ways an organism can respond and adapt to its environment.
Because there has been a strong correlation discovered between methylation and cancer, what types of carcinogens might cause hypermthylation? What specific genes would be methylated, and how does their lack of expression potentially cause cancer? If the lack of expression in these genes causes cancer, is there a specific type? Also, how can our knowledge of methylation in genes help lower the number of cancer patients in the future?
(Vivian To vivto4@students.d125.org)
Moalem describes a potential carcinogen in bethel nuts and how "a lifetime of betel nut chewing can lead to hypermethylation of three cancer-fighting genes—one that suppresses tumors, one that repairs DNA, and one that hunts out lone cancer cells and gets them to self-destruct" (Moalem 173). According to the article "Association of Betel Nut with Carcinogenesis: Revisit with a Clinical Perspective," the carcinogen is mainly alkaloids, and a gene that was affected is the p53 gene (Rajeshwar et al.). According to the article "p53 : The Most Frequently Altered Gene in Human Cancers," the p53 gene is a tumor suppressor gene and is repressed by the MDM2 protein (Vogelstein, Sur, and Prives). Veogelstein, Sur, and Prives explain that people with p53 gene mutations are unable to induce MDM2 which causes "relatively high levels of p53 in tumors" (Vogelstein, Sur, and Prives). According to Rajeshwar et al., a "common trend observed among the varying populations was p53 overexpression and nuclear accumulation of p53 protein" leading to oral cancer. According to Rajeshwar et al., many different DNA repair genes are affected by Betel nuts depending on ethnic background. These genes would be "XRCC4 in Taiwanese population and XRCC1 and XPD in Indian population" (Rajeshwar et al.). The methylation of DNA repair genes would allow many mutations to occur in various genes like the p53 tumor suppressor gene. The tumor suppressor gene may be mutated by a missense mutation that changes an amino acid in the p53 protein which allows tumors to grow. The methylation of genes that hunt out cancer cells would allow a single cancer cell to reproduce causing tumors which would lead to a resurgence of cancer.
ReplyDeleteMoalem explains how doctors can determine the methylation of cancer fighting genes to "decide if chemotherapy is necessary after the tumor is removed" (Moalem 172). This would prevent unnecessary cell death with chemotherapy and would result in personalized treatment. Also by determining if cancer fighting genes are methylated, doctors can demethylate those genes and prevent cancer. People can also avoid things that hypermethylate their genes and thus prevent cancer that way.
This idea relates to Big Idea 3, living systems store, retrieve, transmit, and respond to information essential to life process, because MDM2 turns off p53 expression which shows an example of negative feedback. The cell determines when there is enough p53 and then uses MDM2 to stop producing p53. This also relates to Big Idea 4, biological systems interact, and these systems and their interactions possess complex properties, because p53 reacts to an overabundance of cells by inducing apoptosis to prevent tumors.
Association of Betel Nut with Carcinogenesis: Revisit with a Clinical Perspective:
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0042759
p53 : The Most Frequently Altered Gene in Human Cancers:
http://www.nature.com/scitable/topicpage/p53-the-most-frequently-altered-gene-in-14192717
(Name: Will Han email: wihan4@students.d125.org)