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Cancer Detection: Sometimes The Nose Knows

Cancer stinks more than we do – really. And apparently it stinks so much that some dogs can be trained to smell it.

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Body odor is a billion-dollar industry. Perfumes, deodorants, cosmetics: We spend a tremendous amount of time and money eradicating body odor.

OK, why in the world are we discussing BO in Oncology Outlook?  Cancer stinks more than we do – really. And apparently it stinks so much that some dogs can be trained to smell it.

Body odors are unique among individuals and the type of odor is influenced by a specific pattern of antigens arising from the major histocompatibility complex (MHC) genes. While many of us know about the role of MHC proteins in host immunity, there is a growing body of evidence suggesting that the pattern of MHC proteins may help us diagnose cancer.

The MHC patterns of proteins are known to differ within the bodily fluids (urine, sweat, saliva) and offer a new opportunity for cancer screening.

As a cancer grows, invades surrounding tissues or metastasizes, it creates an inflammatory environment. Cell walls are destroyed and numerous lymphocytes and macrophages are attracted to the region. Additional cytokines and lymphokines are released, affecting cellular metabolism in various  locations, such as in the liver's production of cytochrome P-450 oxidase enzymes.

Cell-membrane fragments are broken down into fatty acids. The peroxidation of the polyunsaturated fatty acids in the liver produces alkanes and methylalkanes. These volatile organic compounds dissolve in body fluids (blood, urine, sweat) and evaporate easily within the lung.

Dogs have a keen sense of smell.  For centuries, they have tracked prey, missing children, weapons of mass destruction and gels in your carry-on luggage.  Dogs can detect certain chemicals in the parts per trillion range.

So the notion that dogs could detect VOCs more accurately than a machine has intrigued many investigators. In late 2005, researchers in Portugal demonstrated that dogs could detect VOCs in the breath of people with cancer.

Changes in the breath pattern of VOCs were associated with different cancers. In one evaluation, the VOC pattern was slightly better in testing for breast cancer in women than was a mammogram. Lung cancer also produces distinctive VOC patterns and a mechanical method of detection is under development.

The British Medical Journal published a report in 2004 after researchers trained dogs to detect bladder cancer from urine samples. Six dogs of varying ages and breeds underwent a seven-month training course in cancer detection, carried out by trainers from Hearing Dogs for the Deaf.

The group used urine samples from 36 patients with bladder cancer and 108 control samples from cancer-free individuals.

Using a food reward system, dogs were shown seven urine samples and told to lie next to the cancerous one. In the final double-blind study, each dog underwent nine separate tests.  The dogs correctly identified the cancer sample more than 50 percent of the time, more than the 14 percent expected by random chance.

Interestingly, the dogs identified one control urine sample as positive, with the investigators later finding out that the control person had kidney cancer.

The newest cancer sniffing study published in the March 2006 issue of the Journal Integrative Cancer Therapies builds on these prior studies. This study is the first to test whether dogs can detect cancers reliably by sniffing the exhaled breath of cancer patients.

Over a three-week period, five household dogs were trained to detect lung or breast cancer by sniffing the breath of participants. The experiment included 86 cancer patients (55 with lung cancer and 31 with breast cancer) and control samples from 83 healthy patients. Complete staging had been performed by conventional methods (mammogram, CT scan) and none had prior exposure to chemotherapy. Breath samples were collected.

As in the urine study, dogs were asked to lie down next to the sample from cancer patients.

The results were amazing. The dogs correctly identified 99 percent of the lung cancer samples and 88 percent of the breast cancer samples after only three weeks of training.

It's not only cancer that stinks.

A quick search of the research literature shows many other conditions where cell degradation and the release of VOCs could be detected by dogs, such as organ transplant rejection, tuberculosis and congenital neurological disorders.

So when will we see cancer sniffing dogs in the hospital? Can they sniff out canine cancers, too?
The body of work is very new but opens up an exciting area of research for cancer detection and treatment. It lends a new definition to the word "aromatherapy."

Kevin A. Hahn, DVM, Ph.D., Dipl. ACVIM (Oncology), is director of Oncology Services at Gulf Coast Veterinary Specialists, Houston (www.gcvs.com/oncology), and is the oncology consultant for YourNetVet (www.yournetvet.com).

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