Cancer sniffing dogs are in the news again, the result of several recently published studies that suggest that canine snouts can be trained to accurately diagnose cancer.

Dogs have a far stronger sense of smell than humans. While humans have roughly five million olfactory cells in their noses, dogs have about 200 million. Dogs are commonly used by the military and police to locate bombs, drugs, lost people and corpses. For a number of years now, research has also suggested that dogs may be able to accurately detect cancer.

In a relatively small trial published back in 2011, a trained dog was able to correctly identify prostate cancer in 30 out of 33 samples by odor. Urine was obtained from 66 patients referred for elevated PSA or abnormal digital rectal examination and who were then biopsied. Samples from the both groups were dog-tested: 33 patients with cancer and 33 controls whose biopsies were negative. One of those three false positives came from a patient who was later diagnosed with prostate cancer. [1]

Results from a new much larger trial were presented at annual meeting of the American Urological Association (AUA) in May 2014. Researchers at several Italian research institutions investigated the accuracy at which two highly-trained dogs could recognize prostate-cancer in urine samples. The study consisted of 677 participants who were placed in one of two groups: prostate cancer group (n=320) and control group (n=357). The prostate cancer group included patients with prostate cancer ranging from those at a very-low risk to metastatic. The control group included a diverse cohort of healthy subjects affected by non-neoplastic disease or non-prostatic tumors. Two dogs carried did the testing.

The two dogs were able to detect the trace odors left by prostate cancer in the urine of study subjects with an accuracy of 98 percent. Sensitivity and specificity for both were 99 percent and 97 percent respectively. One dog’s accuracy rate was 99%. Sensitivity was 100 %and specificity was 98 %. The second dog’s accuracy rate was 97%. Sensitivity and specificity were 99% and 96%.

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a dog’s nose

 A study from March suggests that dogs may also be able to detect lung cancer. Researchers conducted a prospective study of 93 patients consecutively admitted to hospital with suspected lung cancer. Exhaled breath and urine were sampled before the patients underwent bronchoscopy. A canine olfactory test was performed in a double-blinded manner. Sensitivity and specificity were outcome measures. With 99% sensitivity, the olfactory test demonstrated that dogs have the ability to distinguish cancer patients from healthy individuals. [2]

Cancer cells produce distinct odors that these dogs can smell. Cancer increases oxidative stress, which in turn increases the liver’s production of cytochrome P-450 oxidase enzymes. Cell membranes oxidize and the liver breaks down these rancid fats to excrete them faster. These chemicals known as Volatile Organic Compounds (VOCs), diffuse through the lungs, evaporate and flow out in the breath. Using sensitive instruments, researchers have been able to measure and identify different patterns of VOCs in breath samples from cancer patients compared to those who are cancer-free.

Once this was known, attempts were and still are being made to build machines to measure VOCs for cancer screening. A 2003 study reported that an instrumental breath screening to test for breast cancer was slightly better than mammograms (99.93% versus 99.89%) at saying when someone didn’t have cancer, but mammograms were still more accurate at saying when someone had cancer. [3] This breath test could potentially be employed as a preliminary screen for breast cancer. Starting in the late 1990s, several machines were tested to screen for lung cancer. [4,5]

These ‘electronic noses’ are now being researched to detect a range of cancers including liver [6] , colorectal [7] , head and neck [8] , lung [9] , and breast [10] .

Electronic noses don’t come cheap, these machines are expensive, fussy and constantly need maintenance to ensure their accuracy. Dogs on the other hand are pretty much the opposite of high-tech: they have powerful noses, and are able to detect chemicals in the parts per trillion range, and they come cheap. That dogs could be trained to detect cancer’s distinctive VOCs more accurately than an electronic instrument is not that far fetched an idea. Dogs certainly have proven their mettle at detecting hidden explosives and illicit drugs. No one would think of using a machine to track animals or fugitives cross-country.

The first paper we noticed on using dogs to detect cancer was back in 2004, a study published in the British Medical Journal in which researchers reported that their trained dogs could detect bladder cancer by smelling urine samples. Urine samples from 36 patients with bladder cancer and 108 control samples from cancer-free individuals were used. 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.

In their final exam, a double-blinded experiment, each dog underwent nine separate tests in which they were shown seven urine samples, one of which was cancerous, and told to lie down next to the cancerous one. The dogs correctly identified the cancer sample on 22 out of 54 occasions. This success rate of 41 percent was much higher than the 14 percent predicted from chance alone.[11]

As in the earlier prostate cancer trial, one patient with a still undiagnosed tumor was singled out by the dogs, in this case they were eventually diagnosed with kidney cancer.

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Skye, Poppy and Pace

 

Breath testing began replacing urine sniffing with the publication in March 2006 of the Pine Street Foundations study.

Five household dogs were trained over a 3-week period to detect lung or breast cancer by sniffing the breath of cancer participants. The experiment included 86 cancer patients (55 with lung cancer and 31 with breast cancer) and a control sample of 83 healthy patients. All cancer patients had recently been diagnosed with cancer through biopsy-confirmed conventional methods such as a mammogram, or CAT scan and had not yet undergone any chemotherapy treatment. The dogs were presented with breath samples from the cancer patients and the controls.

The dogs correctly detected 99% of the lung cancer samples, and made a mistake with only 1% of the healthy controls. With breast cancer, they correctly detected 88% of the positive samples, and made a mistake on only 2% of the controls. The study also confirmed that the dogs could detect the early stages of lung cancer and early breast cancer.[12]

Cancer isn’t the only disease that stinks and dogs aren’t the only animal trained to detect disease. Angina produces it’s own smell via VOCs[13]. Schizophrenia[14]              and organ rejection in transplant recipients also produce distinctive VOCs [15]. And dogs aren’t the only animal being trained to detect disease. A giant African rat has been trained to smell out tuberculosis [16].

 

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Poppy and Flynn, Cherry Creek 2013

 

References:

1. Cornu JN, Cancel-Tassin G, Ondet V, Girardet C, Cussenot O. Olfactory detection of prostate cancer by dogs sniffing urine: a step forward in early diagnosis. Eur Urol. 2011 Feb;59(2):197-201. doi: 10.1016/j.eururo.2010.10.006. Epub 2010 Oct 15.

2. Amundsen T, Sundstrøm S, Buvik T, Gederaas OA, Haaverstad R. Can dogs smell lung cancer? First study using exhaled breath and urine screening in unselected patients with suspected lung cancer. Acta Oncol. 2014 Mar;53(3):307-15. doi: 10.3109/0284186X.2013.819996. Epub 2013 Aug 19.

3. Phillips, M. et al. Volatile markers of breast cancer in the breath. Breast J. Jul-Aug;9(4):345.2003.

4. Phillips, M. et al. Volatile organic compounds in breath as markers of lung cancer: a cross-sectional study. Lancet. Jun 5;353(9168):1897-81;1999.

5. Phillips, M. Detection of lung cancer with volatile markers in the breath. Chest. Jun;123(6);1788-92: 2003

6. Release and uptake of volatile organic compounds by human hepatocellular carcinoma cells Mochalski P, Sponring A, King J, Unterkofler K, Troppmair J, Amann A. (HepG2) in vitro. Cancer Cell Int. 2013 Jul 17;13(1):72.

7. de Meij TG, Larbi IB, van der Schee MP, Lentferink YE, Paff T, Terhaar Sive Droste JS, Mulder CJ, van Bodegraven AA, de Boer NK. Electronic nose can discriminate colorectal carcinoma and advanced adenomas by fecal volatile biomarker analysis: proof of principle study. Int J Cancer. 2014 Mar 1;134(5):1132-8.

8. Leunis N, Boumans ML, Kremer B, Din S, Stobberingh E, Kessels AG, Kross KW. Application of an electronic nose in the diagnosis of head and neck cancer. Laryngoscope. 2013 Oct 19.

9. Fu XA, Li M, Knipp RJ, Nantz MH, Bousamra M. Noninvasive detection of lung cancer using exhaled breath. Cancer Med. 2014 Feb;3(1):174-81.

10. Phillips M, Beatty JD, Cataneo RN, Huston J, Kaplan PD, Lalisang RI, Lambin P, Lobbes MB, Mundada M, Pappas N, Patel U. Rapid point-of-care breath test for biomarkers of breast cancer and abnormal mammograms. PLoS One. 2014 Mar 5;9(3):e90226.

11. Willis CM. et al. Olfactory detection of human bladder cancer by dogs: proof of principle study. BMJ. Sep 25;329(7468):715;2004.

12. McCulloch M, Jezierski T, Broffman M, Hubbard A, Turner K, Janecki T. Diagnostic accuracy of canine scent detection in early- and late-stage lung and breast cancers. Integr Cancer Ther. 2006 Mar;5(1):30-9.

13. Phillips M, Cataneo RN, Greenberg J, Grodman R, Salazar M. Breath markers of oxidative stress in patients with unstable angina. Heart Dis. 2003 Mar-Apr;5(2):95-9.

14. Phillips M, Erickson GA, Sabas M, Smith JP, Greenberg J. Volatile organic compounds in the breath of patients with schizophrenia. J Clin Pathol. 1995 May;48(5):466-9.

15. Studer SM, Orens JB, Rosas I, Krishnan JA, Cope KA, Yang S, Conte JV, Becker PB, Risby TH. Patterns and significance of exhaled-breath biomarkers in lung transplant recipients with acute allograft rejection. J Heart Lung Transplant. 2001 Nov;20(11):1158-66.

16. McKee M. Giant rats to sniff out tuberculosis. NewScientist.com news service 17:31 16 December 2003

 

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