Exhaled breath collected from 177 volunteers (patients with lung, colon, breast, and prostate cancers and healthy controls) was examined by gold nanoparticle nanosensor arrays (GNPs) and gas chromatography linked to the mass spectrometry technique (GC-MS).
GNP sensor resistance responses showed remarkable separation between cancer and healthy controls (Principal Component Analysis results are shown in the Figure: LC, lung cancer; CC, colon cancer; BC, breast cancer; PC, prostate cancer).
Most of the VOCs reported in this study appear for the first time in the literature, adding to the wide spectrum of chemicals previously proposed as cancer biomarkers. Some of the chemicals - predictive of lung and prostate cancers - are frequently released to the environment through petroleum spills.
1-methyl-4-(1-methylethyl)-benzene - known as p-cymene or p-isopropyltoluene - is utilized by various species for chemical communication. It can be derived from the essential oils of herbs and spices and has biocidal properties against foodborne pathogens such as spoilage yeasts and E. coli O157:H7. p-cymene is the biological precursor of carvacrol that is also an antimicrobial agent (Kiskó and Roller, 2005). It's decreased with cancer, and is present at higher concentrations in healthy individuals.
Toluene, dodecane and other aromatic components of petroleum are among chemicals found in human breath.
Typical "octane booster" toluene - present at higher concentrations in lung and prostate cancers - is toxic to living organisms although some bacteria (like P. putida that has toluene operon) are able to grow in its presence (Eaton 1997).
Dodecane, a biogasoline component, is higher in the breath of healthy individuals. It is decreased in lung cancer. One of its derivatives - 2,6,11-trimethyl-dodecane was found in 80% of the males, but in none of the females participating in the study.
Another aromatic compound, 2-amino-5-isopropyl-8-methyl-1-azulenecarbonitrile, similar to carbonitriles used in manufacturing of fragrance agents, is present at higher concentrations in breast, colon and prostate cancers when compared to healthy controls.
An alcane 3,7-dimethyl-undecane was found to be indicative of allergies. It was previously found to be eliminated from mice odors when they enter reproductive cycle (Achiraman & Archunan, 2006) and proposed to be used in diagnostics of asthma (Dragonieri et al., 2007).
Chemicals in breath can tell not only about cancers, but also relate to other diseases, environmental exposures and dietary behavior. This might decrease discriminative power of expensive metabolomics technologies and bioinformatics approaches not based on additional knowledge, yet custom-made sensor arrays show great promise.
References
Peng G, Hakim M, Broza YY, Billan S, Abdah-Bortnyak R, Kuten A, Tisch U, & Haick H (2010). Detection of lung, breast, colorectal, and prostate cancers from exhaled breath using a single array of nanosensors. British journal of cancer, 103 (4), 542-51 PMID: 20648015
Gabriella Kiskó, Sibel Roller. (2005) Carvacrol and p-cymene inactivate Escherichia coli O157:H7 in apple juice. BMC Microbiol. 2005; 5: 36
Eaton RW. (1997) p-Cymene catabolic pathway in Pseudomonas putida F1: cloning and characterization of DNA encoding conversion of p-cymene to p-cumate. J Bacteriol. 1997 May;179(10):3171-80.
Shanmugam Achiraman, Govindaraju Archunan (2006) 1-Iodo-2methylundecane, a putative estrus-specific urinary chemo-signal of female mouse (Mus musculus) Theriogenology 66, 1913–1920
Dragonieri S, Schot R, Mertens BJ, Le Cessie S, Gauw SA, Spanevello A, Resta O, Willard NP, Vink TJ, Rabe KF, Bel EH, Sterk PJ. (2007) An electronic nose in the discrimination of patients with asthma and controls. J Allergy Clin Immunol. 120(4):856-62.