NBC Nightly News aired an intriguing story last night about dogs who have the ability to detect ovarian cancer [1]. The story referenced a new study published in the European Respiratory Journal that focused on canine scent detection for the diagnosis of lung cancer [2].

The outcome of a patient with lung cancer, like many other cancers, depends in large part on early diagnosis. Exhaled breath of patients may represent the ideal lab specimen for cancer screening. However, current diagnostic sensor technologies are unable to identify a clear target. German scientists used four sniffer dogs to test the strength of the presence of an as-of-yet unknown compound in the breath of patients with lung cancer.

That as-of-yet unknown compound is a biomarker — a protein or set of proteins specific to lung cancer that, by nature of the tumor being in a patient’s lungs, is exhaled.

In the study, researchers had patients with blow into test tubes filled with a fleece material that absorbs compounds suspended in the breath. Following a rigid scientific protocol, sniffer dogs were presented with exhalation samples from either 110 healthy individuals, 60 patients with confirmed lung cancer or 50 patients with chronic obstructive pulmonary disease (COPD). The dogs were trained to lie down next to test tubes that came from patients with lung cancer. Scientists analyzed patient history, drug administration and clinicopathological data to identify potential bias or confounders.

The results are impressive. Lung cancer was identified by the four dogs with an overall sensitivity of 71% and a specificity of 93%.

The detection of lung cancer was independent of the patient having COPD as well as the presence of tobacco smoke and food odors.

Although two drugs were identified as potential cofounders — meaning the dogs may have been detecting drugs used to treat lung cancer rather than the cancer itself — the results are still intriguing. Researchers are working on a follow-up study to determine if the dogs react to other types of cancer [3].

Check out a video of the NBC News story below:

References

1. Trained dogs can help detect cancer. NBC Nightly News. 2011 Aug 18.
2. Ehmann et al. Canine scent detection in the diagnosis of lung cancer: Revisiting a puzzling phenomenon. Eur Respir J 2011. Published ahead of print.
3. Fine dog noses sniff out lung cancer. Robert-Bosch-Krankenhaus. 2011 Aug 18.

The ACS has just wrapped up their first ever video contest on YouTube, where they asked people to create videos – one minute or less – to discourage smoking. You can check out the contest winners at the American Cancer Society.

You can also read more about the harmful effects of smoking and tobacco smoke in these articles here at Highlight HEALTH:

• Smoking Duration vs. Intensity and the Impact on Lung Cancer Risk
• Irreversible Gene Expression Changes From Smoking
• Smoking Cessation Timeline: What Happens When You Quit
• Second-hand Smoke Exposure Linked to Psychological Problems in Children

Accept the Great American Smokeout Challenge.
Quit for one day, or quit for good.

References

1. Cigarette smoking among adults–United States, 2006. Centers for Disease Control and Prevention (CDC). MMWR Morb Mortal Wkly Rep. 2007 Nov 9;56(44):1157-61.
   View abstract

• Smoking Cessation Timeline: What Happens When You Quit
• Irreversible Gene Expression Changes From Smoking

One of our readers asked a question I’m sure many have us have wondered about at one time or another:

Which is worse for the development of lung cancer — smoking heavily over a short period of time or smoking fewer cigarettes over many years?

Here’s what the research has to say:

In 2003, researchers at Memorial Sloan-Kettering Cancer Center created a prediction tool that can assess a long-term smoker’s absolute risk of developing lung cancer within 10 years. How long and how much people have smoked, as well as how long it’s been since their last puff, affect the risk of getting lung cancer.

The formula for the study was published in the Journal of the National Cancer Institute. I’ve linked to the full article since it’s publicly available. The study uses a number of predictors, including age, duration of smoking, average amount smoked per day while smoking and duration of abstinence from smoking (for former smokers) [1]. These predictors are not only identifiable from a clinical history but they are established or strongly suspected risk factors for lung cancer. Additionally, they are also risk factors for all-cause mortality.

Figure 1 models multivariable relations between 1-year lung cancer risk and (A) duration of smoking, (B) average number of cigarettes smoked per day, (C) duration of abstinence and (D) age. In panel A, the relative risk of lung cancer increases exponentially with duration of smoking. In contrast, panel B shows that the relative risk of lung cancer tends to level off between 30 and 60 cigarettes smoked per day.

What does this mean? It means that the relative risk of tobacco-attributable lung cancer sharply increases with increasing duration of smoking, much more so than smoking intensity (i.e. the number of cigarettes smoked per day).

The model for the prediction tool was derived from data collected during CARET, a multicenter, randomized, controlled study that evaluated the impact of beta-carotene and vitamin A supplementation on lung cancer incidence and mortality [2]. Unfortunately, the prediction tool only works for people age 50 and older who smoked at least 10 cigarettes a day for at least 25 years, since those were the people tracked for cancer development in the study.

Further research found that the model described above slightly underestimated the observed risk of lung cancer over 10 years [3]. I choose to write about this particular study because of the accessibility of the online prediction tool. However, other risk models have been developed [4-6].

Additional studies have also suggested that smoking duration has a stronger effect in the prediction of lung cancer risk than number of cigarettes smoked per day [7-10]. These models are consistent with the results from epidemiologic studies, which indicate that risks of lung cancer, as well as bladder cancer, tend to level off with increased smoking intensity [11].

Smoking cessation at any age is beneficial. Nevertheless, lower lung cancer death risk is observed for people who quit at younger ages [12]. Indeed, cessation of smoking prior to middle age is associated with a more than 90% reduction in cancer risk attributed to tobacco [13].

This isn’t to say that smoking intensity isn’t a major contributor to tobacco-attributable cancer risk. However, the take-home message is that long-term smoking clearly impacts lung cancer risk to a greater extent. That’s why it’s more important than ever to quit smoking now.

References

1. Bach et al. Variations in lung cancer risk among smokers. J Natl Cancer Inst. 2003 Mar 19;95(6):470-8.
   View abstract
2. Omenn et al. The beta-carotene and retinol efficacy trial (CARET) for chemoprevention of lung cancer in high risk populations: smokers and asbestos-exposed workers. Cancer Res. 1994 Apr 1;54(7 Suppl):2038s-2043s.
   View abstract
3. Cronin et al. Validation of a model of lung cancer risk prediction among smokers. J Natl Cancer Inst. 2006 May 3;98(9):637-40.
   View abstract
4. Peto et al. Smoking, smoking cessation, and lung cancer in the UK since 1950: combination of national statistics with two case-control studies. BMJ. 2000 Aug 5;321(7257):323-9.
   View abstract
5. Prindiville et al. Sputum cytological atypia as a predictor of incident lung cancer in a cohort of heavy smokers with airflow obstruction. Cancer Epidemiol Biomarkers Prev. 2003 Oct;12:987-93.
   View abstract
6. Cassidy et al. Defining high-risk individuals in a population-based molecular-epidemiological study of lung cancer. Int J Oncol. 2006 May;28(5):1295-301.
   View abstract
7. Doll and Peto. Cigarette smoking and bronchial carcinoma: dose and time relationships among regular smokers and lifelong non-smokers. J Epidemiol Community Health. 1978 Dec;32(4):303-13.
   View abstract
8. Peto, R Influence of dose and duration of smoking on lung cancer rates. Zaridze, D Peto, R eds. Tobacco: a major international health hazard; proceedings of an international meeting Moscow, USSR, June 4-6, 1985. 1986 World Health Organization, International Agency for Research on Cancer Lyon, France. International Agency for Research on Cancer Science Publication No. 74, 23-33.
9. Flanders et al. Lung cancer mortality in relation to age, duration of smoking, and daily cigarette consumption: results from Cancer Prevention Study II. Cancer Res. 2003 Oct 1;63(19):6556-62.
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10. Lubin and Caporaso. Cigarette smoking and lung cancer: modeling total exposure and intensity. Cancer Epidemiol Biomarkers Prev. 2006 Mar;15(3):517-23.
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11. Vineis et al. Levelling-off of the risk of lung and bladder cancer in heavy smokers: an analysis based on multicentric case-control studies and a metabolic interpretation. Mutat Res. 2000 Jul;463(1):103-10.
    View abstract
12. Halpern et al. Patterns of absolute risk of lung cancer mortality in former smokers. J Natl Cancer Inst. 1993 Mar 17;85(6):457-64.
    View abstract
13. Peto et al. Smoking, smoking cessation, and lung cancer in the UK since 1950: combination of national statistics with two case-control studies. BMJ. 2000;321:323-329.
    View abstract

Xenobiotics

A xenobiotic is a chemical found in an organism that is not normally produced or expected to be present in that organism. For example, antibiotics are considered to be xenobiotics in humans because the human body does not produce them and they would not be expected to be present in the body. Other xenobiotics include chemical carcinogens, insecticides, petroleum products and other environmental pollutants. In the body, xenobiotic metabolism is responsible for the removal of xenobiotics. Xenobiotics are metabolized in a two-phase process that typically occurs in the liver. Phase I reactions involve the addition or unmasking of a functional polar group (meaning that one end of the molecule is more positively charged while the other is more negatively charged) on the xenobiotic. In the second phase, glutathione, glucuronic acid or sulphuric acid is conjugated (meaning the union of a substance with a normal constituent of the body) to the xenobiotic and facilitates excretion. The cytochrome P450 enzymes, a superfamily of more than 160 known proteins, catalyze many reactions involved in drug metabolism and are important Phase 1 enzymes.

Gene Expression Changes

Genes associated with airway mucosal response were found to be strongly involved with airway epithelium repair and regeneration. Many of the genes involved in airway repair and regeneration have varying degrees of reversibility. Following smoking cessation, reversible gene expression changes included Trefoil factor 3 (gene symbol TFF3), a structural component of mucus that is elevated in inflammatory response, Ectonucleoside triphosphate diphosphohydrolase 8 (gene symbol ENTPD8), an enzyme involved in nucleic acid metabolism that may play a role in the chemical formation of DNA adducts and Calcium binding tyrosine-(Y) phosphorylation regulated (gene symbol CABYR), a newly discovered bronchial protein that may be involved in ciliary function associated with muco-ciliary clearance response within the lungs.

Gene expression changes that were partially reversible included Mucin 5 (gene symbol MUC5AC), a mucin gene and extracellular matrix structural constituent.

Gene expression changes that were irreversible consisted of functionally diverse genes but included a small number related to the cell cycle and DNA repair. The expression of P21/Cdc42/Rac1-activated kinase 1 (gene symbol PAK1), a protein that regulates cell motility and morphology, and Cyclins D1 (gene symbol CCND1) and G2 (gene symbol CCNG2), proteins that function as regulatory subunits for cell cycle progression, all appeared to be irreversibly lower in both current and former smokers relative to those who had never smoked. Additionally, APEX nuclease (multifunctional DNA repair enzyme) 1 (gene symbol APEX1), High-mobility group box 1 (gene symbol HMGB1), REV1-like (gene symbol REV1) and Tumor suppressor candidate 4 (gene symbol TUSC4) are DNA repair genes that were found to be irreversibly under-expressed in both current and former smokers.

Although CABYR gene expression was found to be reversible, one of its few known interactions occurs with another gene called Glycogen synthase kinase 3 beta (gene symbol GSK3B). Although GSK3B was not identified in the primary analysis, it too is irreversibly reduced in current and former smokers. GSK3B has been shown to negatively interact with Cyclooxygenase 2 (gene symbol COX2), an enzyme responsible for inflammation and pain [1]. The authors suggest that its reduced expression may account for the exaggerated inflammatory response despite smoking cessation and may contribute to the development of lung cancer [2].

According to the first author [3] of the study:

Those genes and functions which do not revert to normal levels upon smoking cessation may provide insight into why former smokers still maintain a risk of developing lung cancer.

Indeed, until recently, many smoking cessation timelines showed that, after 10 years of not smoking, the risk of cancer was that of people who had never previously smoked. However, statistics show an increased risk of lung cancer, even after a decade of not smoking. Age at cessation has a major impact on subsequent lung cancer risk. Although the risk of lung cancer is higher for former smokers than for those who have never smoked, lower lung cancer death is observed for people that quit earlier in life [4].

Your best bet? Don’t start smoking in the first place. If you do smoke, now is the time to quit.

References

1. Thiel et al. Expression of cyclooxygenase-2 is regulated by glycogen synthase kinase-3beta in gastric cancer cells. J Biol Chem. 2006 Feb 24;281(8):4564-9. Epub 2005 Dec 21.
   View abstract
2. Chari et al. Effect of active smoking on the human bronchial epithelium transcriptome. BMC Genomics. 2007 Aug 29;8(1):297 [Epub ahead of print]
   View abstract
3. Smoking Turns On Genes — Permanently. Science Daily. 2007 Aug 30.
4. Halpern et al. Patterns of absolute risk of lung cancer mortality in former smokers. J Natl Cancer Inst. 1993 Mar 17;85(6):457-64.
   View abstract