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Tumor Discovery Volatile organic compounds for cancer screening

heptanal, octanal, and nonanal). A predictive model was and causing as many as 1.1 million deaths annually by
developed using these four biomarkers to differentiate 2030. 25-27
between 24 healthy controls, 17 patients with benign It has been well established that early detection of colon
tumors, and 22 patients with breast cancer. Using this cancer is associated with significantly better outcomes
model, they reported an area under the curve (AUC) of and lower health-care costs. 8,27-30 Colon cancer is typically
0.934, a sensitivity of 91.7%, and a specificity of 95.8%. diagnosed after the onset of symptoms through screening,
The biological significance of individual VOCs remains colonoscopy, or stool testing. Unfortunately, over 86% of
unclear. Some have been shown to be cancer biomarkers colon cancers in patients under 50 years old are symptomatic
21
(i.e., heptanal), while analogs of others have been shown at diagnosis, associated with advanced disease and poor
to have anti-tumor properties (i.e., 2,3-dihydro-1-phenyl- outcomes. 25-29 Indeed, despite strong recommendations for
4(1H)-quinazolinone). Similarly, analogs of 1-phenyl- screening, global participation rates and compliance with
22
ethanone inhibit the invasion of human MCF-7/6 screening remain as low as 1.9 – 54%. 30-34
mammary carcinoma cells in vitro. 23 Colon cancer screening tools include stool-based
Previous studies of patients with lung cancer suggest that testing to detect hemoglobin or DNA alterations
the pattern of exhaled VOCs is associated with accelerated suggestive of malignancy, direct visualization with
catabolism of otherwise benign metabolic by-products, endoscopy, and radiologic imaging. Stool-based
which in turn has been correlated to the induction of screening includes immunochemical tests (fecal
cytochrome P450 enzymes. The aromatase enzyme, which immunochemical test [FIT]), guaiac-based fecal occult
24
34
acts as an estrogen synthase, is a cytochrome P450 enzyme blood tests (gFOBT), and multitarget fecal DNA testing.
complex that acts as a catalyst for estrogen production. Stool-based screening tests for colon cancer are more
The induced cytochrome P450 activity associated with sensitive to the detection of cancer than pre-cancerous
breast cancer may thus influence the pattern of VOCs in polyps. 30-33 FIT testing involves the evaluation of a single
exhaled breath. It is also likely that some VOCs found stool sample, with a specificity of 96.4% and a sensitivity
24
to be increased in breast cancer result from ongoing of 73.8% for the detection of colon cancer. 29-31,33-34 It is only
inflammatory oxidative stress, including lipid peroxidation 23.8% sensitive for the detection of adenomas >10 mm
of fatty acids. Pentane, a lipid peroxidation reaction and 7.6% for adenomas <10 mm. 29-32
24
product, is well described as a VOC that is found in higher gFOBTs are 92.5% specific and 70% sensitive for the
levels in patients with breast cancer. 18,24 Aldehydes, well diagnosis of colon cancers, but the sensitivity is only 23.9%
described as increasing in the exhaled breath of patients for adenomas >10 mm and <12.4% for smaller adenomas. 29-30
with breast cancer, are also secondary reaction products of Multitarget stool DNA testing is more sensitive than other
lipid peroxidation. stool-based screening tests, with a sensitivity of 92.3% and
Strong evidence supports the use of exhaled VOCs a specificity of 89.8% for the detection of colon cancer. 29-34
to accurately detect breast cancer. While the individual It offers improved sensitivity for the detection of adenomas,
molecules described may not be specific to breast cancer, which is reported at 42.4% for adenomas >10 mm and
it is the expression patterns that are diagnostic, leading 17.2% for adenomas <10 mm. 29-34
to the description of validated unique “breathprints” Any patient with an abnormal screening test currently
that combine up to 30 exhaled VOCs. VOC analysis is requires a follow-up colonoscopy. A colonoscopy is
intrinsically safe, painless, and inexpensive and may be both a diagnostic and therapeutic tool, allowing for
superior in sensitivity and specificity when compared to the examination and treatment of the rectum, colon,
screening mammograms. Confirmatory clinical studies and proximal terminal ileum. It is the definitive test
in human populations are required to confirm these for detecting pre-cancerous adenomas and CRC,
preliminary findings. with a specificity reported at 86%. 22,27,29-33 It is 75%

3. Colon cancer sensitive for the detection of adenomas <5 mm, 85% for
adenomas 6 – 9 mm, and 95% for adenomas >10 mm
Colon cancer is the third most common malignancy (Figure 1). 22,27,29-33 Disadvantages of colonoscopy
and remains a leading cause of cancer-related deaths as a screening test include patient discomfort, the
worldwide. 25-28 There are over 1.9 million new diagnoses inconvenience of bowel preparation, and the potential
26
32
and 930,000 deaths annually from colon cancer. The for procedural and sedation-related complications.
global burden of colon cancer is expected to increase Procedural risks include the possibility of a perforated
by 60%, representing at least 2.2 million new cases visceral organ, significant bleeding, and infection. 29-33

Volume 3 Issue 2 (2024) 5 doi: 10.36922/td.2061