Colorectal cancer screening with odour material by
canine scent detection
Hideto Sonoda,1,6Shunji Kohnoe,1,6Tetsuro Yamazato,2Yuji Satoh,3Gouki Morizono,4
Kentaro Shikata,5Makoto Morita,6Akihiro Watanabe,6Masaru Morita,1
Yoshihiro Kakeji,1Fumio Inoue,4Yoshihiko Maehara1
Objective Early detection and early treatment are of vital
importance to the successful treatment of various
cancers. The development of a novel screening method
that is as economical and non-invasive as the faecal
occult blood test (FOBT) for early detection of colorectal
cancer (CRC) is needed. A study was undertaken using
canine scent detection to determine whether odour
material can become an effective tool in CRC screening.
Design Exhaled breath and watery stool samples were
obtained from patients with CRC and from healthy
controls prior to colonoscopy. Each test group consisted
of one sample from a patient with CRC and four control
samples from volunteers without cancer. These five
samples were randomly and separately placed into five
boxes. A Labrador retriever specially trained in scent
detection of cancer and a handler cooperated in the
tests. The dog first smelled a standard breath sample
from a patient with CRC, then smelled each sample
station and sat down in front of the station in which
a cancer scent was detected.
Results 33 and 37 groups of breath and watery stool
samples, respectively, were tested. Among patients with
CRC and controls, the sensitivity of canine scent
detection of breath samples compared with conventional
diagnosis by colonoscopy was 0.91 and the specificity
was 0.99. The sensitivity of canine scent detection of
stool samples was 0.97 and the specificity was 0.99.
The accuracy of canine scent detection was high even
for early cancer. Canine scent detection was not
confounded by current smoking, benign colorectal
disease or inflammatory disease.
Conclusions This study shows that a specific cancer
scent does indeed exist and that cancer-specific
chemical compounds may be circulating throughout the
body. These odour materials may become effective tools
in CRC screening. In the future, studies designed to
identify cancer-specific volatile organic compounds will
be important for the development of new methods for
early detection of CRC.
Despite rapid progress in examination technology
and therapy for colorectal cancer (CRC), this
disease constitutes a significant proportion of the
global burden of cancer morbidity and mortality.1
Multiple professional organisations have recom-
mended screening for CRC1e5and many previous
studies have demonstrated the cost-effectiveness of
familial adenomatous polyposis or Lynch syndrome
are recommended to undergo frequent colonoscopy
to reduce the morbidity and mortality associated
with CRC.12e15Early detection and early treat-
ment are critical for the successful treatment of
cancer and are excellent means for reducing both
1Department of Surgery and
Science, Kyushu University at
Fukuoka, Fukuoka, Japan
2Department of Internal
Medicine, Arita Kyoritsu
Hospital at Arita, Saga, Japan
3St. Sugar Cancer Sniffing Dog
Training Center at
Minamibousou, Chiba, Japan
4Department of General
Surgery, Arita Kyoritsu Hospital
at Arita, Saga, Japan
5Department of Internal
Medicine, Fukuoka Dental
College Hospital at Fukuoka,
6Department of General
Surgery, Fukuoka Dental College
Hospital at Fukuoka, Fukuoka,
Dr Hideto Sonoda, Department
of Surgery and Science
Graduate School of Medicine
Kyushu University 3-1-1
812-8582, Japan; hsonoda@
Revised 23 November 2010
Accepted 7 December 2010
Published Online First
31 January 2011
This paper is freely available
online under the BMJ Journals
unlocked scheme, see http://
Significance of this study
What is already known about this subject?
< Canine olfactory detection of cancer has been
reported for melanoma as well as bladder, lung,
breast and ovarian cancer.
< It is reported that dogs can be trained to
distinguish breath samples of patients with lung
and breast cancer from those of control
volunteers and to distinguish ovarian cancer
tissues from control tissues with high accuracy.
< Several volatile organic compounds have been
identified as candidate substances for early
detection of cancer using gas chromatography/
mass spectroscopy in the exhaled breath of
patients with lung and breast cancer; while
these data are promising, they are preliminary
findings that should be interpreted with caution.
What are the new findings?
< In patients with colorectal cancer (CRC) and
controls, the sensitivity of canine scent detec-
tion of breath samples compared with conven-
tional diagnosis by colonoscopy was 0.91 and
the specificity was 0.99.
< The sensitivity of canine scent detection of
watery stool samples was 0.97 and the
specificity was 0.99.
< The accuracy of canine scent detection was
even higher for early-stage cancers.
< Canine scent detection was not confounded by
current smoking, benign colorectal disease,
inflammatory disease or the presence of
human haemoglobin or transferrin.
How might it impact on clinical practice in the
< Odour materials may become effective tools in
CRC screening. In the future, studies designed
to identify cancer-specific
compounds will be important for the develop-
ment of new methods for early detection of
< Identification of cancer-specific volatile organic
compounds will lead to solving the biological
character of cancer.
814Gut 2011;60:814e819. doi:10.1136/gut.2010.218305
the economic burden and mortality. CRC therefore represents an
excellent example of the value of early detection.
The faecal occult blood test (FOBT) is currently the most
economic and non-invasive screening method for CRC, and
many patients with positive results subsequently undergo total
colonoscopy leading to a reduced incidence and mortality of
CRC.2 3 6 16However, the positive predictive value of FOBT for
CRC is approximately 10%,17e20 16 21considering the impact of
closer examination by colonoscopy or barium enema. The devel-
opment of a novel more effective CRC screening method that is
as economical and non-invasive as FOBT is therefore needed.
There have been several anecdotal reports of canine scent
detection of skin cancer.22 23Moreover, Willis et al reported that
dogs can distinguish urine from patients with bladder cancer
with a mean success rate of 41%,24while McCulloch et al
reported that ordinary household dogs can be trained to distin-
guish breath samples of patients with lung and breast cancer
from those of control volunteers with high accuracy (sensitivity
and specificity of 0.99 and 0.99 in lung cancer and 0.88 and 0.98
in breast cancer, respectively).25Horvath et al reported that,
among ovarian cancer tissues and control tissues, the sensitivity
was 100% and the specificity was 97.5%.26
In the present study we have confirmed the accuracy of canine
scent detection of breath samples and evaluated canine scent
detection of watery stool samples from patients with CRC. We
also examined whether the diagnostic performance of dogs is
affected by age, smoking, disease stage, cancer site, inflamma-
tion or bleeding in patients with cancer or control individuals.
Patient and control sample donors
Patients were enrolled from 20 June 2008 to 20 May 2009 at the
Fukuoka Dental College Medical and Dental Hospital and Arita
Kyoritsu Hospital. To prepare for colonoscopy, subjects ingested
2 l of a balanced electrolyte and polyethylene glycol 4000 solu-
tion (Niflec, Ajinomoto Pharma, Tokyo, Japan). Patients were
required to be >20 years old. Patients and controls completed
a questionnaire about factors that could influence volatile
molecules in the breath or watery stool samples including age,
physical symptoms (eg, abdominal pain or distention, bloody
faeces, constipation, diarrhoea, body weight loss and abdominal
tumour), history of cancer treatment, present use of anticoagu-
lants and smoking within the previous 2 weeks. Colorectal
diseases diagnosed primarily by colonoscopy were recorded in
detail and pathological examination of biopsy samples was
performed if necessary. Patients who had undergone cancer
surgery within the previous year, those who did not undergo
examination for cancer recurrence despite having undergone
cancer surgery more than 5 years previously and those currently
receiving chemotherapy were excluded. A serial number was
written on each sample at the time of collection to identify
Breath samples were acquired from the beginning to the end of
exhalation. Each subject exhaled between 100 and 200 ml into
a breath sampling bag (Otsuka Pharmaceutical Company, Tokyo,
ordinary grocery store Ziploc-style bags at 48C until presentation
to the dog. Only one sample was collected from each participant.
Watery stool sampling
A 50 ml watery stool sample was obtained by suction during
colonoscopy using a trachea aspirator kit (Sumitomo Bakelite
Company, Tokyo, Japan) between the rectum and descending
colon and preserved at ?808C until filtration. The sample was
filtered with qualitative filter paper No. 2 (diameter 110 mm;
Tokyo Roshi Kaisha, Tokyo, Japan) and further filtered by Millex
GP filter (pore size 0.22 mm, diameter 33 mm, non-sterile type;
Millipore Co, Corrigiwohill, Co. Cork, Ireland). Next, 1 ml of
filtrated watery stool samples was enclosed in a 5 ml brown
glass screw cap bottle, sealed in an ordinary grocery store small
Ziploc-style bag and enclosed in a 50 ml polypropylene screw
cap tube and kept at ?208C until presentation to the dog. Only
one sample was collected from each participant.
Dog and training
A specially trained 8-year-old female black Labrador retriever
from the St Sugar Cancer Sniffing Dog Training Center (Chiba,
Japan) participated in the study. The dog was trained for water
rescue beginning in 2003 and then began training as a cancer
detection dog in 2005.
Each cancer detection training session was considered
complete when the dog could correctly distinguish between
breath samples from a cancer patient and four controls consec-
utively in dozens of trials. The fundamental training method
was a reward-based approach in which the correct behaviour is
rewarded by simultaneous play with a tennis ball. The breath
samples used in the training steps beginning in 2005 were
collected from several hundred patients with cancer and about
500 healthy volunteers recruited using the internet.
In the first training step in 2005, breath samples from one
patient with oesophageal cancer and four controls were used.
The samples were removed from the breath-sampling bag and
placed into a paper cup which was then covered with a paper
filter for 2 days. The five sample cups were placed on the floor by
the handler. First, the dog smelled the standard breath sample
from the patient with oesophageal cancer and then tried to
identify the cup containing the oesophageal cancer scent from
among the five sample cups. If the dog correctly identified the
cancer sample it was rewarded with a tennis ball. A similar
training session was conducted using breath samples from
patients with lung cancer on the following day and was
performed again using breath samples from patients with gastric
cancer 2 days later.
In the second step the breath-sampling bag was used with the
end cap on. Breath-sampling bags containing oesophageal, lung
or gastric cancer scents originating from the same patient in
the first step were chosen randomly for the 1-month training
In the third step the dog first smelled the breath sample from
one type of cancer as a standard sample and then tried to
identify the bag with the scent of another cancer. The training
was then continued by adding samples of other types of cancers
as well as controls.
The dog was already able to detect the following types of
cancer in patient breath samples prior to initiation of the present
study: oesophageal cancer, breast cancer, lung cancer, gastric
angiocarcinoma, colorectal cancer, prostate cancer, uterine
cancer, ovarian cancer and bladder cancer.
Training and test room
The training and testing of the dog were conducted in
a 4.8 m38.0 m room with vinyl tiling and overhead fluorescent
and natural window lighting. The room was not climate
controlled and average ambient temperatures during the study
(November 2008 through June 2009) ranged from 98C to 208C.
Gut 2011;60:814e819. doi:10.1136/gut.2010.218305 815
At the end of each study day the floor was wiped with water
and a damp mop.
Five sample stations were positioned on the floor of the room in
a single straight line spaced 52 cm apart. Each station consisted
of a light blue painted wooden storage container measuring
27 cm wide, 30 cm long and 20 cm high. Each station also
contained a wall 10 cm deep in which the breath sample bags or
the watery stool sample bottles were placed. The top of each
box was covered with metal netting to prevent the dog from
directly contacting the samples.
Breath and watery stool sample locations
In a single trial, the dog passed and sniffed each of the five
stations (one cancer sample and four control samples). Both
patient and control samples were replaced with new samples
after the dog had sniffed all five sample stations. Two to four
trials were performed on each day of testing.
The dog handler called the dog into the room and encouraged
the dog to sniff the stations with the command ‘Search!’ after
smelling the standard breath sample from the patient with CRC
at each test. No other people were in the room.
Classification of the dog’s response
Correct responses were (1) indication by sitting down in front of
a sample station containing a cancer sample (a true positive in
sensitivity calculations): and (2) sniffing but not indicating on
a control sample (true negative). Incorrect responses were (1)
indicating on a control sample (false positive); (2) sniffing but
not indicating on a cancer sample (false negative); and (3)
hesitation, considered to be an incomplete reaction to either
cancer or control samples (either false positive or false negative
depending on whether hesitation was on a cancer or control
Tests were conducted from 13 November 2008 to 15 June 2009
because the dog’s concentration tends to decrease during the hot
summer season. For each test, completely new samples were
used for both cases and controls; thus, each sample was only
used a single time. For each trial we used a random number table
to determine the location of the sample being tested in the line-
up. Before the tests the sample was placed in either a new bag or
new bottle to avoid contamination of the smell under preser-
vation, and the number described in the sample was converted
from the serial number into the test number at the same time.
The laboratory assistants replaced the samples. The identity of
the samples was blinded to the dog, the handler and the labo-
ratory assistants, thereby making the study double-blind. One
station contained a cancer sample and the remaining four
stations contained control samples. At the tests the dog smelled
the standard breath sample of CRC origin, after which the dog
passed the side of some boxes and sat down in front of the
station determined to contain a cancer scent, and then the
handler noted the result on an answer card on which the test
number was written. The card was transmitted to Fukuoka
Dental College by fax. After submission the answer was
explained to the handler and the dog as soon as possible because
the correct behaviour was rewarded with a tennis ball. The
cards were collected by mail. During the tests the dog did not
experience any adverse events, injuries or illness.
Occult blood test of watery stool samples
The ordinary FOBT kit, Quick Chaser Occult Blood Test Kit
(Mizuho Medy, Saga, Japan) was used for simultaneous detec-
tion of human haemoglobin and human transferrin in watery
stool samples. Watery stool samples were mixed with phosphate
buffered saline and reacted on the test plate. The test result was
judged by a laboratory medical technologist and a physician.
The result was defined as positive when human haemoglobin
and/or transferrin was positive.
Associations between questionnaire variables before colono-
scopy were tested by the Welch t test or c2test. All statistical
differences of p<0.05 were deemed significant. CRC staging was
based on Union Internationale Contre le Cancer (UICC) criteria.
During testing, experimenters monitored each trial and
recorded their observations on a digital versatile disc. The entire
dog performance dataset was audited for accuracy by comparing
answer cards with digital versatile disc records.
Diagnostic accuracy was calculated as sensitivity and speci-
ficity of the dog’s indication of samples compared with the true
diagnosis confirmed by colonoscopy. Thus, the sensitivity (or
the true positive rate) of the tests is the proportion of cancer
samples correctly identified by the dog while the specificity (or
the true negative rate) is the proportion of control samples
negatively indicated by the dog.
Forty-eight samples were obtained from patients with CRC, 203
samples from volunteers with no history of cancer and 55
samples from patients with a previous history of cancer. For
breath tests, 33 samples from patients with CRC and 132
samples from control volunteers were used and, for watery stool
tests, 37 samples were used from patients with CRC and 148
during testing. The background characteristics were well
matched between cancer patients and control individuals, except
for age (table 1). Approximately half of the controls (47% of
breath samples, 50% of watery stool samples) had colorectal
polyps and a small proportion of the controls (6.1% of breath
samples, 10.5% of watery stool samples) had bleeding or
inflammatory colorectal disease, including ischaemic colitis, non-
peculiar colitis or ulcer, ulcerative colitis, diverticular bleeding,
mesenteric panniculitis and chronic appendicitis (table 2).
Diagnostic accuracy: sensitivity and specificity in testing
To calculate sensitivity and specificity we designated the dog’s
response to each sample sniffed as the unit of analysis (defined
above). Comparison of the judgement of the canine scent in the
breath or watery stool samples with a colonoscopy-confirmed
conventional diagnosis among cancer patients and controls gave
an overall sensitivity for canine scent detection of 0.91 and 0.97,
respectively, while the overall specificity was 0.99 and 0.99,
respectively (table 3).
During the course of 74 tests, four discrepancies occurred
between colonoscopy and the canine scent detection results
(1/38 watery stool tests and 3/36 breath tests). The discrep-
ancies occurred in the 22nd, 26th, 33rd and 45th tests. Moreover,
these discrepancies occurred in any of four tests on the afore-
mentioned test days. Interestingly, the watery stool sample that
yielded a discrepancy came from an individual whose breath
sample also resulted in a discrepancy. Samples from the three
patients who did not have colon cancer but whose samples
yielded positive results in the watery stool and/or breath tests
816Gut 2011;60:814e819. doi:10.1136/gut.2010.218305
did not result in discrepancies on the other tests. These three
patients showed no signs of cancer during the 24 months
Comparison between FOBT results and the dog’s judgement
The results of watery stool tests and conventional FOBTs were
compared to determine whether canine scent judgement relied
on blood. No correlation between canine scent judgement and
FOBT results was observed in patients with cancer (p¼0.51) or
controls (p¼0.68, table 4). The sensitivity and specificity of
FOBT with respect to CRC detection was 0.70 and 0.85,
Mixture test of watery stool samples
To determine whether a specific cancer scent exists or if a partic-
ular natural scent vanishes in patients with cancer, we combined
five watery stool samples into single mixture samples. One of
the mixture samples was composed of one sample of cancer
origin and four control samples, while four mixture samples
times as described above. Cancer types included stage IIIa
ascending colon cancer, stage II transverse colon cancer and
stage 0 rectal cancer. The results of all three tests were correct.
We used the excellent ability of dogs to distinguish between
different scents to examine whether odour materials can be used
in the diagnosis of CRC. This study represents the first step
towards the development of an early detection system using
odour materials from patients with CRC.
McCulloch et al previously reported the use of canine scent
judgement of breath samples for distinguishing between
controls and patients with lung and breast cancer.25We there-
fore evaluated canine scent detection of CRC first with breath
samples and then with watery stool samples, which has not
been previously reported. We hypothesised that the watery stool
sample scent might be strong because the samples were collected
from nearer to the cancer than were the breath samples.
Conversely, the watery stool sample scents might have been
masked by various other scents such as short-chain fatty acids
and sulfides present in the stool. Moreover, we were able to
compare scent detection with the FOBT by using the same stool
sample and to inspect it more quantitatively than using breath
samples. Indeed, despite various disrupting scents, the watery
stool sample tests were superior to the breath sample tests.
We compared the accuracy of canine scent judgement with
colonoscopic diagnosis using breath samples and watery stool
samples from patients with CRC and controls. For breath tests,
the sensitivity and specificity was 0.91 and 0.99, respectively
and, for watery stool tests, the sensitivity and specificity was
0.97 and 0.99, respectively. Moreover, canine scent judgement
even appeared to be highly accurate for early-stage CRC.
Canine scent judgement was not confounded by current
smoking, benign colorectal polyps, inflammation or infection. A
statistically significant difference in age distribution was noted
between cancer patients and controls (p¼0.001 for breath tests,
p<0.05 for watery stool tests). We therefore reanalysed samples
from patients and controls aged <80 years. In this subset anal-
ysis, no correlation between age and cancer status was observed
(p¼0.09 for 19 breath tests, p¼0.93 for 24 watery stool tests).
The sensitivity and specificity in this subset analysis for breath
tests was 0.95 and 0.99, respectively, while the sensitivity and
specificity were both 1.00 for watery stool tests.
There were four discrepancies among the 74 tests including
one of 38 watery stool tests and three of 36 breath tests between
the colonoscopy and canine cancer detection results. It is diffi-
cult to specify the cause of these discrepancies owing to their
limited number. The discrepancies occurred in the 22nd, 26th,
33rd and 45th tests, not necessarily in the early tests. Moreover,
these discrepancies occurred in any of the four tests on the
aforementioned test days, not necessarily in those taken late in
the day. No correlation between the discrepancies and training
effect or fatigue was suspected. Interestingly, the watery stool
Background characteristics of participants
Breath samples Watery stool samples
(n[148)p Valuep Value
Complaint before colonoscopy
Abdominal pain or distention
Body weight loss
Past history of colorectal disease
Smoked within 2 weeks
Disease in control cases
Breath samples Watery stool samples
Non-peculiar colitis or ulcers
Multiple answers were allowed for benign disease.
Gut 2011;60:814e819. doi:10.1136/gut.2010.218305817
sample that yielded a discrepancy came from an individual
whose breath sample also resulted in a discrepancy. Moreover,
when the watery stool test was repeated with different controls,
the dog hesitated a few times and then barely detected the rectal
cancer sample, leading to negative results in both the breath and
watery stool tests. It is thought that some cancers are difficult to
detect by canine scent.
No correlation between canine scent judgement and human
haemoglobin and transferrin was observed. Thus, canine scent
judgement does not appear to depend on human haemoglobin or
transferrin scents. All canine scent judgements of watery stool
sample mixture tests were correct, indicating that a specific cancer
scent indeed exists. The volatile organic compounds (VOCs)
detected during canine scent judgement presumably occur early in
the pathogenesis of CRC. As canine scent judgement can be used
on both breath samples and watery stool samples, these chem-
ical compounds may be circulating throughout the body.
To determine whether a specific cancer scent exists or if
a particular natural scent disappears in patients with cancer,
mixtures that included watery stool samples were tested. Tests
were performed three times as described above. The results of all
three tests were correct, thereby suggesting that a specific cancer
scent indeed exists.
Canine scent judgement for distinguishing between cancer
patients and controls has been reported for other cancer
types.24e26We obtained breath and watery stool samples from
patients with breast, stomach and prostate cancer who also
underwent colonoscopy. We also tested these samples using
breath samples from patients with CRC as the standard. Canine
scent judgement yielded correct answers for these cancers as
well (data not shown), suggesting that common scents may
exist among various cancer types. This is consistent with the
results of McCulloch et al which demonstrated the utility of
canine scent detection for lung and breast cancer25; however,
these results are not inconsistent with the existence of cancer-
It may be difficult to introduce canine scent judgement into
clinical practice owing to the expense and time required for the
dog trainer and for dog education. Scent ability and concentra-
tion vary between different dogs and also within the same dog
on different days. Moreover, each dog can only conduct tests for
a maximum of 10 years. It is therefore necessary to identify the
cancer-specific VOCs detected by dogs and to develop an early
cancer detection sensor that can be substituted for canine scent
Breath VOCs have been reported as biomarkers of other
gastrointestinal disorders such as inflammatory bowel disease,
ulcerative colitis and necrotising enterocolitis.27e30However,
these tests have not been widely accepted, largely due to tech-
nical difficulties in measuring the pressure of exhaled VOCs, the
large variations in food intake, the variability in the required
time for bacterial colonisation and the poor predictive value of
a positive test.
Several VOCs have been identified as candidate substances for
early detection of cancer using gas chromatography/mass spec-
troscopy (GC/MS) in the exhaled breath of patients with lung
and breast cancer31e38; while these data are promising, they are
preliminary findings that should be interpreted with caution. We
intend to evaluate these VOCs by chemical analysis and with
cancer detection dogs in the near future. Identification of cancer-
specific VOCs will lead to solving the biological character of
cancer. We hope that the results of the present study will provide
encouragement for the development of cancer detection and
solving the biological character of cancer using odour material.
Acknowledgements The authors thank Tomoe Fujino and Mika Ohnishi for their
valuable technical assistance. The sponsor of the trial had no role in the design or
conduct of the study, or in the analysis of the data. The corresponding author had
full access to the data and had final responsibility for the decision to submit the data
for publication. No compensation was given to subjects for providing breath
samples or watery stool samples.
Funding This study was funded by Fukuoka Dental College.
Competing interests None.
Ethics approval This study was conducted with the approval of the institutional
review boards at Fukuoka Dental College and Arita Kyoritsu Hospital and all subjects
provided written informed consent.
Provenance and peer review Not commissioned; externally peer reviewed.
Boyle PLB, ed. World Cancer Report 2008. Lyon, France: IARC Press, 2008.
US Preventive Services Task Force. Screening for colorectal cancer: U.S.
Preventive Services Task Force recommendation statement. Ann Intern Med
haemoglobin and transferrin
Relationship between canine scent detection and human
Judgement by faecal
occult blood test
p Value PositiveNegative
Accuracy of canine scent detection by site and stage of cancer
Breath samples Watery stool samples
0I IIIIIIV Total0I IIIII IV Total
3/3 4/5*2/2 1/1
Number of true positives/total test number are shown.
R+S, double rectal and sigmoid colon cancer.
818 Gut 2011;60:814e819. doi:10.1136/gut.2010.218305
3. Download full-text
Winawer SJ, Zauber AG, Fletcher RH, et al. Guidelines for colonoscopy surveillance
after polypectomy: a consensus update by the US Multi-Society Task Force on
Colorectal Cancer and the American Cancer Society. Gastroenterology
US Preventive Services Task Force. Screening for colorectal cancer:
recommendation and rationale. Ann Intern Med 2002;137:129e31.
Rex DK, Johnson DA, Lieberman DA, et al. Colorectal cancer prevention 2000:
screening recommendations of the American College of Gastroenterology. American
College of Gastroenterology. Am J Gastroenterol 2000;95:868e77.
Walsh JM, Terdiman JP. Colorectal cancer screening: clinical applications. JAMA
Frazier AL, Colditz GA, Fuchs CS, et al. Cost-effectiveness of screening for
colorectal cancer in the general population. JAMA 2000;284:1954e61.
Sonnenberg A, Delco F, Inadomi JM. Cost-effectiveness of colonoscopy in
screening for colorectal cancer. Ann Intern Med 2000;133:573e84.
Park SM, Yun YH, Kwon S. Feasible economic strategies to improve
screening compliance for colorectal cancer in Korea. World J Gastroenterol
Shimbo T, Glick HA, Eisenberg JM. Cost-effectiveness analysis of strategies for
colorectal cancer screening in Japan. Int J Technol Assess Health Care
Wagner JL, Herdman RC, Wadhwa S. Cost effectiveness of colorectal cancer
screening in the elderly. Ann Intern Med 1991;115:807e17.
Lynch HT, Lynch JF, Attard TA. Diagnosis and management of hereditary colorectal
cancer syndromes: Lynch syndrome as a model. CMAJ 2009;181:273e80.
Kievit W, de Bruin JH, Adang EM, et al. Cost effectiveness of a new strategy to
identify HNPCC patients. Gut 2005;54:97e102.
Lynch HT, de la Chapelle A. Hereditary colorectal cancer. N Engl J Med
Ramsey SD. Screening for the Lynch syndrome. N Engl J Med 2005;353:524e5;
author reply 525.
Mandel JS, Church TR, Bond JH, et al. The effect of fecal occult-blood screening on
the incidence of colorectal cancer. N Engl J Med 2000;343:1603e7.
UK Colorectal Cancer Screening Pilot Group. Results of the first round of
a demonstration pilot of screening for colorectal cancer in the United Kingdom. BMJ
Hamilton W, Round A, Sharp D, et al. Clinical features of colorectal cancer
before diagnosis: a population-based case-control study. Br J Cancer
Manfredi S, Piette C, Durand G, et al. Colonoscopy results of a French regional
FOBT-based colorectal cancer screening program with high compliance. Endoscopy
Steele RJ, McClements PL, Libby G, et al. Results from the first three rounds of the
Scottish demonstration pilot of FOBT screening for colorectal cancer. Gut
Ahlquist DA, Wieand HS, Moertel CG, et al. Accuracy of fecal occult blood
screening for colorectal neoplasia. A prospective study using Hemoccult and
HemoQuant tests. JAMA 1993;269:1262e7.
Williams H, Pembroke A. Sniffer dogs in the melanoma clinic? Lancet 1989;1:734.
Church J, Williams H. Another sniffer dog for the clinic? Lancet 2001;358:930.
Willis CM, Church SM, Guest CM, et al. Olfactory detection of human bladder
cancer by dogs: proof of principle study. BMJ 2004;329:712.
McCulloch M, Jezierski T, Broffman M, et al. Diagnostic accuracy of canine scent
detection in early- and late-stage lung and breast cancers. Integr Cancer Ther
Horvath G, Jarverud GA, Jarverud S, et al. Human ovarian carcinomas detected by
specific odor. Integr Cancer Ther 2008;7:76e80.
Cheu HW, Brown DR, Rowe MI. Breath hydrogen excretion as a screening test for
the early diagnosis of necrotizing enterocolitis. Am J Dis Child 1989;143:156e9.
Pelli MA, Trovarelli G, Capodicasa E, et al. Breath alkanes determination in ulcerative
colitis and Crohn’s disease. Dis Colon Rectum 1999;42:71e6.
Tibble JA, Sigthorsson G, Foster R, et al. Use of surrogate markers of inflammation
and Rome criteria to distinguish organic from nonorganic intestinal disease.
Pelton NS, Tivey DR, Howarth GS, et al. A novel breath test for the non-invasive
assessment of small intestinal mucosal injury following methotrexate administration
in the rat. Scand J Gastroenterol 2004;9:1015e16.
O’Neill HJ, Gordon SM, O’Neill MH, et al. A computerized classification technique
for screening for the presence of breath biomarkers in lung cancer. Clin Chem
Phillips M, Cataneo RN, Ditkoff BA, et al. Prediction of breast cancer using volatile
biomarkers in the breath. Breast Cancer Res Treat 2006;99:19e21.
Preti G, Labows JN, Kostelc JG, et al. Analysis of lung air from patients with
bronchogenic carcinoma and controls using gas chromatography-mass spectrometry.
J Chromatogr 1988;432:1e11.
Phillips M, Cataneo RN, Ditkoff BA, et al. Volatile markers of breast cancer in the
breath. Breast J 2003;9:184e91.
Gordon SM, Szidon JP, Krotoszynski BK, et al. Volatile organic compounds in
exhaled air from patients with lung cancer. Clin Chem 1985;31:1278e82.
Phillips M, Greenberg J. Method for the collection and analysis of volatile
compounds in the breath. J Chromatogr 1991;564:242e9.
Phillips M. Breath tests in medicine. Sci Am 1992;267:74e9.
Phillips M, Sabas M, Greenberg J. Increased pentane and carbon disulfide in the
breath of patients with schizophrenia. J Clin Pathol 1993;46:861e4.
Gut 2011;60:814e819. doi:10.1136/gut.2010.218305819