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Posts Tagged ‘early detection’


Populations with Low Cancer Risk, Implications for Early Detection Research

Curator: Stephen J. Williams, Ph.D.

Amish Have Lower Rates Of Cancer, Ohio State Study Shows

Report from Ohio State University
COLUMBUS, Ohio – When Ohio State University cancer researchers first began studying a large sect of Amish living in Ohio, they theorized they would find higher incidence rates of cancer. That’s because Amish religious beliefs and traditions limit contact with mainstream society, and intermarriage within this relatively small population could increase the incidence of cancer-related gene mutations.

Instead, they found just the opposite, said Dr. Judith Westman, division director of Human Genetics at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC-James).

The study of Amish suggests that clean living can lead to healthier life. Overall cancer rates in this population were 60 percent of the age-adjusted rate for Ohio and 56 percent of the national rate. The incidence of tobacco-related cancers in the Amish adults was 37 percent of the rate for Ohio adults, and the incidence of non-tobacco-related cancer was 72 percent.

“The Amish are at an increased risk for a number of genetic disorders but they probably have protection against many types of cancer both through their lifestyle – there is very little tobacco or alcohol use and limited sexual partners – and through genes that may reduce their susceptibility to cancer,” said Westman, who co-authored the study with OSUCCC-James researcher Amy K. Ferketich, who specializes in epidemiology.

The findings were reported in a recent issue of the journal Cancer Causes & Control. The study, which spanned 1996-2003 and is the first of its kind, looked at the incidence of 24 types of cancer in the Amish population. Of the 24 types of cancer studied, the incidence of seven of them – cervical, laryngeal, lung, oral cavity/pharyngeal, melanoma, breast and prostate – was low enough compared with the Ohio rate to be statistically significant.

Westman and Ferketich chose to study the Amish to gain a better understanding of the contributions of environment and genetics to developing cancer. Ohio is home to the largest Amish population in the world, and of the approximately 26,000 Amish living in Holmes County, all descended from the same 100 people who immigrated here 200 years ago.

Researchers interviewed 92 Amish families as part of a cross-sectional household survey and charted their family cancer histories obtaining cancer information on all relatives back three generations and as far forward as possible. For example, researchers interviewing a set of grandparents could gather cancer information on both their ancestors and descendants, said Ferketich.

The study population consisted of 9,992 Amish adults residing in the Holmes County area. Researchers also collected death certificates and cross-checked cancer cases reported to the Ohio Cancer Incidence and Surveillance System. Between 1996 and 2003, there were 191 incident cancer cases identified.

“Because this is a small, relatively closed population, we needed to interview just 92 families to cover 90 percent of the population in Holmes County,” said Ferketich.

The low cancer incidence in the Ohio Amish may be partially explained by lifestyle factors such as limited tobacco consumption and lack of sexual promiscuity. The Amish, as a whole, consume very little tobacco and alcohol, and they lead active, labor-intensive lives as farmers, construction laborers and factory workers.

“One of the things we can learn from the Amish is that they don’t typically smoke or use tobacco products,” Westman said. “They have limited sexual partners and monogamous relationships, so they don’t have some of the cancers that are related to sexual promiscuity.”

Even skin cancer rates are lower for Amish, despite the fact though many Amish make their living working outdoors where they are exposed to sunlight and UV rays.

“They are typically covered and dress to work in the sun the way that is recommended by wearing wide-brimmed hats and generally wearing long sleeves to protect their arms,” Westman said.

Other Ohio State researchers involved in the study include Steven N. MacEachern, J.R. Wilkins III, Robert T. Pilarski, Rebecca Nagy, Stanley Lemeshow, Albert de la Chapelle and Clara D. Bloomfield.

The study was funded by the Ohio Division of the American Cancer Society, National Institutes of Health and the Leukemia Clinical Research Foundation.

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Author/ Curator:  Tilda Barliya PhD

I was recently amazed to read about a young teen who scooped the headlines with his story: Jack Andraka created an early detection test for pancreatic cancer (PC) (1). While we extensively discussed pancreatic cancer in previous posts (1b), this one deserve it’s on attention.

Andraka tells the audience about his journey from learning about a the  family member  diagnosed with PC, to a flash insight while learning about carbon nanotubes during a biology class, through the screening and finding one protein out of thousands and all the way up his final discovery. His journey wasn’t easy to say the least, he story though deserve all the applause.

Starting with his journey, Andraka began by “looking for a protein in the bloodstream that would be a biomarker for pancreatic cancer, one that would be found in all cases, even in the earliest stages”. He finally narrowed it down to the one that could work – Mesothelin.

So what is mesothelin?

Model for peritoneal metastasis of ovarian tumors. A model showing the importance of MUC16-mesothelin interaction in the peritoneal metastasis of ovarian tumors is shown.

Gubbels JA, et al. Mol. Cancer (2006). Model for peritoneal metastasis of ovarian tumors.

Mesothelin is a 4o kDa secreted protein expressed in normal mesothelial cells and over-expressed in several human tumors including mesothelioma, ovarian and pancreatic adenocarcinoma (2,3). Although the full mechanism by which mesothelin work is still unsolved, it is postulated thought, that mesothelin growth and apoptosis of pancreatic cancer cells by a p53 -dependent and independent pathways (7).

Andraka’s method:

human mesothelin-specific antibodies  were mixed with single walled carbon nanotubes and used to coat strips of ordinary filter paper. This made the paper conductive. The optimal layering was determined using a scanning electron microscope.  Cell media spiked with varying amounts of mesothelin was then tested against the paper biosensor and any change in the electrical potential of the sensor strip (due to the changing conductivity of the nanotubes) was measured, before and after each application.

The antibodies would bind to the mesothelin and enlarge. These beefed-up molecules would spread the nanotubes farther apart, changing the electrical properties of the network: The more mesothelin present, the more antibodies would bind and grow big, and the weaker the electrical signal would become.

A dose-response curve was constructed with an R2 value of .9992. Tests on human blood serum obtained from both healthy people and patients with chronic pancreatities, pancreatic intraepithelial neoplasia (a precursor to pancreatic carcinoma), or pancreatic cancer showed a similar response. The sensor’s limit of detection sensitivity was found to be 0.156 ng/mL; 10 ng/mL is considered the level of overexpression of mesothelin consistent with pancreatic cancer. Andraka’s sensor costs $0.03 (to compare to a $800 cost of a standard test) and 10 tests can be performed per strip, taking 5 minutes each. The method is 168 times faster, 26,667 times less expensive, and 400 times more sensitive than ELISA, and 25% to 50% more accurate than the CA19-9 test (5).

More so, Wang K and colleagues showed that inhibition of mesothelin may be used as novel strategy for targeting cancer cells (6). The authors showed that silencing the MSLN gene, encoding for mesothelin, inhibits cell proliferation and invasion. While this work is very impressive, the authors haven’t evaluated the potential use these siRNA in animal studies.

In summary:

It is very exiting to know that we may now have a simple and cheap blood test that has the huge potential to save many lives. All we need to do now is to conduct a multinational large scale screening for potential patients.

Andraka on his part is very hopeful, he believes  “it could potentially be used to test for ovarian and lung cancer too. And by switching out the protein the test reacts to, it could — down the road — be used for diseases as varied as heart disease and HIV/AIDS”.

Ref:

1. By: Kate Torgovnich . An early detection test for pancreatic cancer: Jack Andraka at TED2013.http://blog.ted.com/2013/02/27/an-early-detection-test-for-pancreatic-cancer-jack-andraka-at-ted2013/

1b. By; Tilda Barliya PhD. Pancreatic Cancer: Genetics, Genomics and Immunotherapy. https://pharmaceuticalintelligence.com/2013/04/11/update-on-pancreatic-cancer/

2. Mesothelin. http://en.wikipedia.org/wiki/Mesothelin

3. Nathalie Scholler. Mesothelin. http://www.med.upenn.edu/schollerlab/user_documents/Scholler%20Encyclopedia%20of%20Cancer%202008.pdf

4. Argani P, Iacobuzio-Donahue C, Ryu B, Rosty C, Goggins M, Wilentz RE, Murugesan SR, Leach SD, Jaffee E, Yeo CJ, Cameron JL, Kern SE and Hruban RH. Mesothelin is overexpressed in the vast majority of ductal adenocarcinomas of the pancreas: identification of a new pancreatic cancer marker by serial analysis of gene expression (SAGE). Clin Cancer Res. 2001 Dec;7(12):3862-3868. http://clincancerres.aacrjournals.org/content/7/12/3862.long

5. Jack Andraka and Glen Burnie, MD. A Novel Paper Sensor for the Detection of Pancreatic Cancer. http://apps.societyforscience.org/intelisef2012/project.cfm?PID=ME028&CFID=28485&CFTOKEN=10931553

6. Wang K, Bodempudi V, Liu Z, Borrego-Diaz E, Yamoutpoor F, et al. (2012) Inhibition of Mesothelin as a Novel Strategy for Targeting Cancer Cells. PLoS ONE 7(4): e33214. doi:10.1371/journal.pone.0033214. http://www.plosone.org/article/info:doi/10.1371/journal.pone.0033214

7.  Zheng C, Jia W, Tang Y, Zhao HL, Jiang Y and Sun S.  Mesothelin regulates growth and apoptosis in pancreatic cancer cells through p53-dependent and -independent signal pathway. Journal of Experimental & Clinical Cancer Research 2012, 31:84.  http://www.jeccr.com/content/pdf/1756-9966-31-84.pdf

Other related articles on this open Access Online Scientific Journal, include the following:

I. Pancreatic cancer genomes: Axon guidance pathway genes – aberrations revealed.

Aviva Lev-Ari, PhD, RN, 10/24/2012

https://pharmaceuticalintelligence.com/2012/10/24/pancreatic-cancer-genomes-axon-guidance-pathway-genes-aberrations-revealed/

II. Biomarker tool development for Early Diagnosis of Pancreatic Cancer: Van Andel Institute and Emory University.

Aviva Lev-Ari PhD,RN, 10/24/2012

https://pharmaceuticalintelligence.com/2012/10/24/biomarker-tool-development-for-early-diagnosis-of-pancreatic-cancer-van-andel-institute-and-emory-university/

III. Personalized Pancreatic Cancer Treatment Option.

Aviva Lev-Ari PhD, RN, 10/16/2012

https://pharmaceuticalintelligence.com/2012/10/16/personalized-pancreatic-cancer-treatment-option/

IV. Battle of Steve Jobs and Ralph Steinman with Pancreatic cancer: How we lost.

Ritu Saxena PhD, 5/21/2012

https://pharmaceuticalintelligence.com/2012/05/21/battle-of-steve-jobs-and-ralph-steinman-with-pancreatic-cancer-how-we-lost/

V.  Early Biomarker for Pancreatic Cancer Identified.

Prabodh Kandala, PhD, 5/17/2012

https://pharmaceuticalintelligence.com/2012/05/17/early-biomarker-for-pancreatic-cancer-identified/

VI. Usp9x: Promising therapeutic target for pancreatic cancer.

Ritu Saxen PhD, 5/14/2012

https://pharmaceuticalintelligence.com/2012/05/14/promising-therapeutic-target-discovered-for-pancreatic-cancer/

VII. Issues in Personalized Medicine in Cancer: Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing.

Stephen J. Williams, PhD, 10/4/2013

https://pharmaceuticalintelligence.com/2013/04/10/issues-in-personalized-medicine-in-cancer-intratumor-heterogeneity-and-branched-evolution-revealed-by-multiregion-sequencing/

VIII. In Focus: Targeting of Cancer Stem Cells.

Ritu Saxena, PhD, 3/27/2013

https://pharmaceuticalintelligence.com/2013/03/27/in-focus-targeting-of-cancer-stem-cells/

IIX. New Ecosystem of Cancer Research: Cross Institutional Team Science.

Aviva Lev-Ari. PhD, RN, 3/24/2013

https://pharmaceuticalintelligence.com/2013/03/24/new-ecosystem-of-cancer-research-cross-institutional-team-science/

IX. In Focus: Identity of Cancer Stem Cells.

Ritu Saxena, PhD, 3/22/2013

https://pharmaceuticalintelligence.com/2013/03/22/in-focus-identity-of-cancer-stem-cells/

 

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