Infections to Cancer

Chronic Infections = Cancer ( 15% of global cancer burden)

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Abstract

Despite awards of 5 Nobel prizes to 9 leading biomedical scientists, the concept of treating some cancer as infectious diseases has not yet gained the public and media attention or acceptance. Infections cause about 21% of the global cancer burden. The carcinogenic infections are caused by mainly herpes viruses, papilloma viruses, retroviruses, hepatitis viruses, bacteria helicobacter pylori and liver flukes and worms. These infectious cancer can be prevented with vaccines and treated with antiviral, antibacterial and antiparasitical agents in a cost effective manner than traditional costly and toxic anticancer drugs. Once again the burden is higher in poor and developing countries (40% of cancer burden) in comparison with Western developed countries (10% of cancer burden). These cancer can be reduced by existing treatment and vaccines and funding new R&D for new safe and effective drugs.

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Introduction

About 21% of global cancer burden is caused by  infections. The incidence of infections related cancer is only 10% in the Western or developed countries. The incidence is a high 40% in Asian, African and Latin American developing countries. In general society and persons living in poor sanitary and hygiene conditions are at higher risk of getting carcinogenic infections. Chronic infections can lead to cancer. The key factors increasing cancer risk are : age of infection, co-infection, smoking, immunocompromised status, malnutrition and poor hygiene. Development of vaccines and antiviral and antiparasitic agents can offer a cost effective treatment and prevention to high cost anticancer drugs. Herpes, Papilloma and retroviruses are the most important human infectious carcinogens. Chronic infection with the bacteria Helicobacter pylori causes stomach cancer.
Header - Cancer can be prevented
World Cancer Day - February 4th

World Cancer Day 4 February, 2011  UICC/WHO

By the year 2020, there will be 16 million new cases of cancer/year, out of which 70% in developing countries.



Each year, over 12 million people receive a cancer diagnosis and 7.6 million die of the disease.

The good news is that approximately 40% of cancers are potentially preventable.


The risk of developing cancer can significantly be reduced through simple measures:

  • Stop tobacco use and avoid exposure to second-hand smoke
  • Limit alcohol consumption
  • Avoid excessive sun exposure
  • Maintain a healthy weight, through eating healthily and exercising regularly
  • Protect against cancer-causing infections

Peyton Rous in 1911 was the first pioneer to show development of chicken sarcoma due to virus infection in 1911. John Bittner in 1936 described the mouse mammary tumor virus. Denis Burkitt described the childhood lymphoma in 1958 and Michael Epstein, Yvonne Barr and Bert Achong identified the etiological agent the herpes virus in 1964. Johannes Fibiger, Denmark won the Nobel prize in 1926 for the role of nematode Ganglyonema neoplasticum in rat tumors. These findings have not been replicated and thus the Nobel prize was a mistake. The involvement of parasites in human cancer is relatively new area. Numerous reports and case reports linking parasites, Schistosoma trematoads and liver flukes with human cancer were published.  Although hepatitis B and C  vaccines were developed to prevent highly prevalent infections, these vaccines have reduced the incidence of liver cancer after years of use in some developing countries.
Harald zur Hausen 
Infections Causing Human Cancer. was 2007. Wiley-VCH: Weinheim. 532p. ISBN: (Hardcover) 9783527310562. US $215



Harold zur Hausen


There are several human cancer where virus infection is suspected and yet to be identified.
These cancer are

Maybe due to HPV type of viruses

Squamous cell carcinoma
Skin cancer
Oral Cavity, tongue, Larynx, Esophagus
Head and Neck


A simian type of SV 40 polyoma virus may be involved in

Brain Tumors
Islet tumors
Testicular cancer

Viral link with medulloblastoma
 
Colon cancer linked to Fusobacteria.
An analysis of these microbial genes in CRC patients showed that a type of bacterium, Fusobacterium, was abundant in the tumors although it normally is not among the more prominent species in the gut. 

Genomic analysis identifies association of Fusobacterium with colorectal carcinoma

  • Aleksandar D. Kostic
  • Dirk Gevers
  • Chandra Sekhar Pedamallu,
  • Monia Michaud
  • Fujiko Duke
  • Ashlee M. Earl
  • Akinyemi I. Ojesina,
  • Joonil Jung
  • Adam J. Bass
  • Josep Tabernero
  • José Baselga
  • Chen Liu,
  • Ramesh A. Shivdasani
  • Shuji Ogino
  • Bruce W. Birren
  • Curtis Huttenhower,
  • Wendy S. Garrett
  • and Matthew Meyerson

Genome Res. Published in Advance October 18, 2011,doi:10.1101/gr.126573.111

Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma

  • Mauro Castellarin
  • René L. Warren
  • J. Douglas Freeman
  • Lisa Dreolini,
  • Martin Krzywinski
  • Jaclyn Strauss
  • Rebecca Barnes
  • Peter Watson,
  • Emma Allen-Vercoe
  • Richard A. Moore
  • and Robert A. Holt

Genome Res. Published in Advance October 18, 2011,doi:10.1101/gr.126516.111





Copy From NCI Visuals Online Images

AV Number: AV-8000-0617

Electron Micrograph Epstein Barr Virus



preview

From CDC PHIL 2982

Leukemia Cells containing Epstein Barr Virus

Nobel Prize Awards in Infections and Cancer

Despite awards of 5 Nobel Prizes to 9 leading medical scientists and current acceptance by the mainstream scientists, the public has still not accepted the perception of cancer as a preventable chronic infection.

Tumor Viruses

1. Peyton Rous, Rockefeller University  identified the first transmissible avian tumor virus in 1910 and showed the cell free transmission of sarcoma in chickens in 1911. 
Rous proof of concept was not accepted by the mainstream science. He was awarded the Nobel Prize  in medicine in 1966, almost 55 years  after the discovery.
Rous sarcoma virus

2. 1975 Nobel Prize in Medicine for interactions between tumor virus and host cells



David Baltimore

David L. Baltimore
Born 7 March 1938
New York City, New YorkUSA
Nationality United States
Fields Biology
Institutions Massachusetts Institute of Technology
Rockefeller University
California Institute of Technology
Alma mater Swarthmore College
Rockefeller University
Known for Reverse transcriptase
Notable awards Nobel Prize in Physiology or Medicine(1975)


http://en.wikipedia.org/wiki/David_Baltimore


http://baltimorelab.caltech.edu/


Howard Martin Temin

Howard Martin Temin
Born December 101934
Philadelphia
Died February 91994
Nationality United States of America
Institutions University of Wisconsin–Madison
Alma mater California Institute of Technology
Known for reverse transcriptase
Notable awards 1975 Nobel Prize in Physiology or Medicine






3. In 1989, J. Michael and Harold Varmus were awarded the Nobel Prize in medicine for the discovery of retroviral oncogenes
Harold Varmus                                      Michael Bishop 
Harold Varmus             bishop1
4. From NobelPrize.org 

The Nobel Assembly at Karolinska Institutet has today decided to award 
The Nobel Prize in Physiology or Medicine for 2008 with one half to

Harald zur Hausen

for his discovery of “human papilloma viruses causing cervical cancer”

and the other half jointly to

Françoise Barré-Sinoussi and Luc Montagnier

for their discovery of “human immunodeficiency virus”


Herald zur Hausen in Heidelberg during the 1972-1980 period, first isolated the HPV type 6 in human genital warts and later detected the presence of HPV 16 in 50% of cervical cancer cells and HPV 18 in 17-20% of cancer cells. The advent of PCR  resulted in rapid detection of the HPV types in cervical cancer and so far over 106 types of viruses have been described. A pharmaceutical company turned down zur Hausen request to develop a vaccine in 1984. It was only in 1991 that the idea of HP virus as a leading cause of cervical vaccine was accepted and industry started development of HPV vaccine.  
Finding the viral link: the story of Harald zur Hausen
Infections Causing Human Cancer (2006) (Print ISBN 9783527310562; Online ISBN 9783527609314)

Harald zur Hausen

Born March 11, 1936 (age 73)
GelsenkirchenGermany
Nationality German
Fields Virology
Institutions German Cancer Research Center
Known for Discovery that HPV can causecervical cancer
Notable awards 2008 Nobel Prize in Physiology or Medicine

From NobelPrize.org

Distribution of cervical cancer

Map

The global public health burden attributable to human papilloma virus is considerable. More than 5% of all cancers worldwide are caused by persistent infection with this virus. Infection by the human papilloma virus is the most common sexually transmitted agent, afflicting 50-80% of the population.

 

YouTube Video

Copy From NCI Visuals Online Images
Human Papilloma Virus
 
 

 

preview     

           

Tumor Bacteria  Helicobacter pylori

5. Robin Warren in 1979 first observed the bacteria in 50% of biopsy samples from patients who had died due to ulcer. A new biopsy study was done by Barry Marshall and Robin Warren in 100 Australian patients to confirm the earlier findings. The bacterium was isolated and cultured for the first time in 1982, Helicobacter pylori, bacteria on the surface of the gastric 

mucosa, are able to survive and persist in spite of gastric acidity and the strong immune response.  They showed that drinking a solution of the bacterium caused strong stomach reaction and it was identified as a cause of chronic inflammatory diseases such as 
gastroduodenal ulcer disease.  

 

This milestone discovery was largely ignored as ulcers were easily cured by 1-2 weeks treatment with H2 blockers and later proton pump inhibitors like Tagamet, Zantac, Prilosec and Nexium. These treatments had high rates of recurrence or relapse or second ulcer. It was only several years later than the merits of it chronic bacterial infection widely accepted, especially in Europe and France in 1995. 

From Royal Perth Hospital 

2005 Nobel Laureates, Professor Barry Marshall (left) and Dr Robin Warren (right)

2005 Nobel Laureates, Professor Barry Marshall and Dr Robin Warren
    
Image Electron Micrograph of Helicobacter pylori
Source 

File:EMpylori.jpg


    The bacteria probably spread directly from person to person orally and is acquired during birth from mother to child.  If an individual is not infected before the age of 10 years, he has very little risk of being later.  Helicobacter pylori are detected in more than 90% of people with duodenal ulcers and in about 80% of those with gastric ulcer.  Infection with Helicobacter pylori is one of the most chronic infections throughout the world: 20 to 90% of adults are infected in different countries.  The infection is more common in developing countries (60 to 80% of the population affected), while it is lowest in the industrialized countries (20 to 50% of the population that is affected, especially those disadvantage).  

A sharp rise in the elderly population is observed.

 

 C – A cancer of the stomach:   

Lymphoma of MALT (Mucosa Associated Lymphoid Tissue) even rarer was his prognosis changed 

since the knowledge of Helicobacter pylori.  




NCI Visuals Online  

AV Number: AV-8000-0285

Endoscopy Diagnosis

  

preview


Worms causing Human Sufferings

Roundworms
Hookworms
Whipworms
Poor sanitation Lack of clean and treated drinking water, treatment of human sewage 
3 billion persons infected mostly in poor developing countries.
Hookworms
Can get into the human body through sweet glands or hair follicles
WHO data   740 million persons infected mostly in Asia, Latin America and Africa
Ascaris Roundworms
WHO  infects 1.5 billion persons
Ascariasis causes 60,000 deaths per year
Whipworm
NIAID
Trichuris trichiura infects 800 million and is linked with Crohn’s disease.
Lymphatic filariae
WHO 120 million infected 40 million disfigured
Schistosomes
200 million infected mostly in Africa
Trichinella, Tapeworm and Pinworm  

Liver Flukes  From UICC 

Opisthorchis viverrini, Opisthorchis felineus, and Clonorchis sinensisis are food-borne flukes that infect the human liver. Opisthorchis viverrini causes cancer in humans.
• Infection occurs by eating raw or undercooked freshwater fish containing the flukes.
• In East Asia and Eastern Europe, liver fluke infection is endemic in many regions. Approximately 600 million people are estimated to be infected.
• Cholangiocarcinoma (cancer of the bile ducts) is a glandular cancer caused by liver fluke infection resulting from chronic inflammation or obstruction of the bile ducts.
• There is no cure for cancer of the bile ducts.
• Prevention and control of infection can be achieved through behavioural changes in diet and health education. 


Causes of worm infections in humans

Poor sanitation
Unsafe water for drinking
Consumption of unwashed fruits, salads and vegetables
Consumption of raw or uncooked meats or fish like Suchi
Treatment of worm infections
R&D for new drug discovery and development limited
Lack of funding
Newer ivermectins not available
Difficult to eliminate parasites due to different life stages
Eggs almost very difficult to eliminate.
WHO emphasis on getting free drug from Merck failed to attract new R&D in antiparasites.



Fact sheets from WHO/TDR: UICC

Schistosomiasis and Bladder Cancer


Schistosomiasis, or bilharzia, is a parasitic disease caused by trematode flatworms of the genus Schistosoma

In the body, the larvae develop into adult schistosomes, which live in the blood vessels. The females release eggs, some of which are passed out of the body in the urine or faeces. 

In urinary schistosomiasis, there is progressive damage to the bladder, ureters and kidneys. 

In intestinal schistosomiasis, there is progressive enlargement of the liver and spleen, intestinal damage, and hypertension of the abdominal blood vessels.

Control of schistosomiasis is based on drug treatment, snail control, improved sanitation and health education.

Schistosomiasis is a parasitic disease that occurs in tropical and subtropical areas of the world. It is the major health risk in the rural areas of Central China and Egypt and continues to rank high in other developing countries.

• Some 600 million people are at risk of becoming infected. It is estimated that 200 million people are already infected.

• Schistosomiasis contributes to 27.6% of bladder cancer. Over 350’000 new cases of bladder cancer are recorded worldwide.

• Extreme poverty, the unawareness of the risks, the inadequacy or total lack of public health facilities plus the unsanitary environment are all factors contributing to the risk of infection.

• Schistosomiasis is an avoidable risk factor which could reduce the burden of bladder cancer in developing

Schistosomiasis by Sherif El Saadany

Histopathological and Immune-Pathological Changes in the Prostates of Golden Hamsters Experimentally Infected With Sc…


http://www.who.int/wormcontrol/en/

Chagas disease (Region of the Americas – PAHO) 

http://www.paho.org/english/hcp/hct/dch/chagas.htm


CDC PHIL 11201 

 Schistosoma mansoni trematodes

PHIL Image 11201



Parasites Causing Cancer

Cancer Drugs#58 Books and MonographsCancer Drugs#58 Books and Monographs

References, Direct Links and Knols 





Updated
Sources, data and images cited and used are mainly from WHO, CDC, NIH  or World Health Day related to the disease

Parasitic Diseases




Links to Official Sites for Cancer an…