The total run time for our grid was 115 hours and 17 minutes since January 1st,  at 3:30 pm. The total points generated was 5,046 and we had 10 results returned. The link to the grid computing web page is:  http://www.worldcommunitygrid.org/viewLogin.do.

Heritability of Breast Cancer

Heritability of Breast Cancer

A study performed by Rowell et al. showed that the instances of monozygotic twins both having breast cancer is higher than the instances of dizygotic twins both having breast cancer.  This information is valuable to our discussion of heritability because twins show levels of concordance.  Monozygotic (identical) twins share 100% of their genes, while dizygotic twins share only about 50% of their genes.  This research indicates that 10% of all breast cancers are heritable because of the prevalence of familial cases. 

Familial cases of breast cancer are most often observed after menopause. Because of the late onset of breast cancer, it usually does not effect the reproductive period of females.  Therefore does not have an affect on the fitness of the affected individual.  Because most individuals have already reproduced offspring before signs of breast cancer appear, selection against traits that may cause breast cancer are not existent.  Many researchers have come to the conclusion that breast cancer is likely passed through autosomal inheritance. 

Another factor that may be a partial cause of breast cancer is dense breast tissue.  Dense breast tissue, when visible on a mammogram, is linked with higher risk of breast cancer.  A study was performed on twins in Australia, Canada, and the United States to find if dense breast tissue is a heritable trait.  The findings showed 65% of the variation in density was due to heritability. 

The gene that codes for breast cancer is believed to be on chromosome 11 in human genome.  Research has shown that deletion of traits of chromosome 11 have a strong correlation with tumors and breast cancer.  The deletion on the short arm of chromosome 11 suggests that recessive mutations may be the underlying cause of breast cancer.  Because cancer is thought to be caused by recessive traits, inbreeding will most likely cause breast cancer to be far more common among the population.

 

References:

Boyd NF, Dite GS, Stone J, Gunasekara A, English DR, McCredie MR, Giles GG, Tritchler D, Chiarelli A, Yaffe MJ,Hopper JL. Heritability of mammographic density, a risk factor for breast cancer.  N Engl J Med. 2002 Sep 19;347(12):886-94.  Division of Epidemiology and Statistics, Ontario Cancer Institute, Toronto, Canada.

Lippman, Marc E., Dickson, Robert Brent. Breast Cancer: Cellular and Molecular Biology.  Springer 1988

Mack, T M;  Hamilton, A S;  Press, M F;  Diep, A; and Rappaport, E B.  Heritable breast cancer in twins   British Journal of Cancer (2002) 87, 294–300. doi:10.1038/sj.bjc.6600429 www.bjcancer.com. Published online 23 July 2002

Rowell S, Newman B, Boyd J, King M-C (1994) Inherited predisposition to breast and ovarian cancer. Am J Hum Genet 55: 861–865 

Questions on Cancer Research

The following question/answer section is part of our Evolution Grid-Computing Project. They all deal with an article we read entitled, “Normal Stem Cells and Cancer Stem Cells: The Niche Matters” by Li and Neaves (2006).

1. In your interview, the oncology nurse agreed that stem cells may be the key to eradicating cancer. This article addresses this perspective as well as its antithesis, as it discusses the role of stem cells in cancer causation. It states that as few as 1 to 2 mutations can change a stem cell into a cancer cell. Remembering that mutations generate variation, how is cancer an evolutionary phenomenon?

The article talks about how somatic cells have to undergo six different mutations in order to become cancerous. This is different from stem cells which only have to undergo two mutations to become cancerous. Based on the principle of Ockham’s Razor, the simplest path is the correct path. This would mean that it is most likely that stem cells are the cells that become cancer cells because it is probably that a population of cells in an individual would undergo two mutations rather than six. Mutation is a form of evolution and if stem cells mutate into cancer cells, more cancer cells will be produced. However the evolution is occurring within an individual. If stem cells mutate into cancer cells, those cells will divide and produce more cancer cells. This will generate variation among the population of cells within an organ.

2. Most genes code for proteins. Given the information in this article and the above question, why is it important to look at protein folding and mis-folding when studying cancer?

By studying and understanding protein folding and mis-folding, researchers believe we can find the cure to many diseases, cancer being one, for example. Thus far this semester we have been involved in a grid-computing project. The efficiency of grid-computing is tremendous and enables many corporations, research teams, and everyday volunteers at home to use cutting-edge technology to aid in information processing. By participating in grid-computing and folding at home projects, everyday people are able to see the significance of protein folding and the consequences of mis-folding. Mis-folding is the result of an error in the genetic blueprint which leads to incomplete folding of that particular protein, which ultimately affects its function. As described in the paper, tumorigenesis is the result of mutations that interfere with the appropriate function of regulatory proteins. This deals with cancer in that tumor suppressors become inactive and lead to cancer as a loss of function phenotype. Therefore, by studying mis-folding of proteins and comparing normal protein folding, researchers can see what mutations are occurring and why. This can lead to more insightful information about cancer’s development and perhaps a cure.

3. In an evolutionary sense, why is it informative to study cancer and its implications in flies or, especially, in mice?

Mice and flies are inexpensive and easy to handle and so are often used in experiments. Also flies and mice reproduce quickly and many generations can be observed. Also there are no laws protecting mice and flies so researchers can do any sort of test without having to document the animals’ safety. There have been several experiments done with mice that have proven that stem cells play a part in perpetuating cancer in organs such as the breasts and the brain. In observing generations of flies and or mice one can see the heritability in cancer and see if cancer undergoes evolution. It is especially informative when studies are done on mice because they have a genome that is closer to ours as humans and we can conclude that the cancer that is observed in mice will react similar to human cancers. Orthology refers to genes in different species that derive from a common ancestor and can be applied to mice and humans. However, these orthologous genes may or may not have the same function.

4. What is a niche in the context of an ecosystem? Is the stem cell “niche” similar, in that different niches impose different selection pressures on the stem cells? Explain how niche control of stem cells is like natural selection.

In terms of an ecosystem, a niche describes how an organism or population responds to the distribution of resources and competitors. A stem cell niche is a special environment in which stem cells reside. The stem cell niche sends signals to the stem cells to inhibit or promote proliferation. We know that stem cells are dependant on the niche because when the niche is lost many stem cells are lost. There are special adhesion molecules that connect a stem cell to its niche. The niche is hypothesized to control stem cells and when they should divide. Niche control is like natural selection because the niche can control which stem cells to divide. Just like natural selection can show selection for or against an allele, the niche can show selection for healthy stem cells or cancerous stem cells to divide and reproduce.

Update!

Our grid has been running very well and we got our first update! the grid that we are running is helping find a cure for childhood cancers! One of these cancers are called Neuroblastoma which arises in children under the age of two with only a 40% survival rate. As we explained the grids were helping scientist learn more about the proteins that help cancer grow. They have completed that research and found that there are three proteins. Now scientist need to search the three million drug candidates for a treatment. Our computer will be helping with just that.
To learn more about Neuroblastoma you can check our our grid Evolution2009 at www.worldcommunitygrid.org.

Interview with Cancer Expert

For our interview with a cancer expert, we chose to interview Barbara Hedgpeth, (RN, OCN) a Radiation-Oncology Nurse at the Kansas City Cancer Center.  This interview took place at 12pm on Sunday, February 15, 2009.

What type of cancer does your team help treat?

I work in radiation/oncology, and we treat solid tumors with radiation. 

 

Can you describe the process of cancer treatment if someone were to obtain it at an early stage?

There are 3 basic ways to treat cancer: surgery, chemotherapy, and/or radiation.  The patient's treatment depends on type of cancer.  A patient may have just one type of treatment, or all 3 depending on the type, location, and the stage.  Stages are 1-4:  1 is early and localized; stage 4 means that the cancer has spread to distant areas of the body.

 

Have you seen a drastic increase in the number of patients you treat with cancer throughout the years?

No, I have not.  The numbers usually remain rather constant.

 

With that said, do you think people are being cautious of cancer and seeing the doctor regularly for check-ups for possible early detection of cancer?

Yes, screenings and treatments for cancer are improving every day.

 

Can you describe the more harsh symptoms of cancer? Have they worsened as time goes on or stayed the same?

The hardest symptoms to see are people in pain or that have trouble breathing.  Symptoms are much better treated with medications.  Pain, nausea, and anti-anxiety medicines are much better and patients are much more comfortable.

 

What makes cancer dangerous? 

Cancer is an uncontrolled growth of cells.  So the abnormal cancer cells interfere with the normal healthy cells in the body.  Cancer can spread from the primary site to other areas in the body and make it very difficult to control. 

 

Are they still finding new types of cancer?  Is this evidence of evolution in cancer? 

 I do not know of any new types of cancer.  There are trends where some types of cancer become more prevelent.  Certain types of cancer are more common in certain age groups, gender, and ethnic groups.  This may be evidence of evolution due to certain traits being carried on in certain people.  For example prostate cancer is more common in African American men.  Asian people have lower rates of cancer.

 

What are some misconceptions about cancer or breast cancer? 

 Cancer is not one disease.  It is many different diseases.  Even in Breast Cancer there are many different cell types, grades, and stages of disease.  The cell type and other factors determine the treatment you will get. 

 

Any interesting stories involving patients with cancer and recovery?   

Every cancer patient has a story, and that is what makes caring for them so interesting.  It is nice to see patients and their families show strength and courage to fight their disease.

 

What made you want to nurse?  Did you ever experience a personal story with relation to cancer that made you want to help others?

I liked biology and have always been a natural care giver.  I enjoy helping and taking care of people.  I decided that I wanted to work with cancer because as a nursing student I worked with cancer patients.  I found that the patients and their families inspired me. 

 For more information or to get in contact with Barbara Hedgpeth, you can email her at barbara.hedgpthe@usoncology.com

Description of Project

In this project, we will download a grid computing application to help aid in the search for a cure for cancer.  We chose this topic to grid compute because breast cancer is a disease that we hold dear to our hearts because it is the national philanthropy of our sorority, Zeta Tau Alpha.  Through our years in Zeta here at Rockhurst we have raised a great deal of money for the Susan G. Komen Foundation for Breast Cancer Research as well as spreading education about the disease to our peers and professeurs.  

There are many grid computing projects already in progress.  Grid computing is a linkage of personal computers to solve complex equations to help find cures for many diseases and other problems.  For this particular project, we downloaded a grid computing application that will process 86 million images of proteins that have been screened in the high-throughput crystallization pipeline.  If you would like to know more, you can visit the grid's website at http://www.worldcommunitygrid.org/projects_showcase/hcc1/viewHcc1Faq.do?shortName=hcc1#313.