by Dr. C.H. Weaver M.D. 11/2022
Quit Smoking - Its Never Too Late
Smoking accounts for a large majority of lung cancer deaths in both men and women, meaning that the best way to reduce the risk of lung cancer is never to smoke. But for both men and women who do smoke, it’s important to realize that quitting smoking provides important lung cancer benefits.1-3
Compared with nonsmokers, women who smoke more than 20 cigarettes per day are roughly 20 times more likely to die of lung cancer.2 For a woman who was a heavy smoker, the risk of dying of lung cancer drops to roughly ninefold higher than a nonsmoker within six to 10 years of quitting and to less than threefold higher by 16 years after quitting. So although it’s true that never-smokers have the lowest lung cancer death rates, women who are smokers can greatly reduce their risk of lung cancer by quitting smoking.
The results of a study published in the British Journal of Cancer indicate that men who quit smoking can significantly reduce their risk of developing lung cancer. The benefit of quitting was found even if men waited until middle age to do so.3
Lung cancer is the most common of all cancers world wide, and smoking can be attributed to 85% of diagnosed cases of lung cancer due to the damage of lungs caused by cigarettes. Factors determining a smoker’s risk include the number of years the person has been smoking, as well as the number of cigarettes smoked each day.
In this study, researchers gathered data from 6,523 patients who had been diagnosed with lung cancer and 9,648 individuals who had not been diagnosed with lung cancer from the United Kingdom, Germany, Italy and Sweden. The risk of developing lung cancer among smokers were between 6%-15% in the UK, Germany, Italy and Sweden. The risk of developing lung cancer was reduced by 80%-91% in men who quit smoking before the age of 40. In further analysis, the risk of developing lung cancer was reduced by 57%-69% in men who quit smoking before the age of 50.3
Avoidance of Secondhand Smoke
Avoidance of secondhand smoke is also important. Secondhand smoke is the third-leading cause of lung cancer in the United States. It is thought to account for roughly 3,000 lung cancer deaths each year.4 Fortunately, policies to eliminate smoking in indoor public places have had a dramatic effect on exposure to environmental tobacco smoke in the United States. Between 1988 and 2002, the percentage of U.S. nonsmokers who had evidence of cotinine in their blood fell from 88 to 43 percent.5 Cotinine is a byproduct of nicotine metabolism and indicates recent exposure to tobacco smoke. Because smoking rates did not change greatly during this time period, these improvements are likely due to a reduction in smoking in public places.
Lung Cancer in Never-smokers
An estimated 15 percent of lung cancer diagnoses among U.S. women occur among women who have never smoked.6 Factors such as secondhand smoke, residential radon exposure, and familial susceptibility are known to contribute to some cases of lung cancer in never-smokers, but the cause of many cases remains unknown.
Lung cancer that develops in never-smokers appears to have different biologic characteristics than lung cancer that develops in smokers. For example, lung cancer in never-smokers tends to be more responsive to drugs such as Tarceva. To further explore the optimal approach to the treatment of lung cancer in never-smokers, a handful of clinical trials are now focusing specifically on never-smokers. Continued research into the ways in which lung cancer in never-smokers differs from lung cancer in smokers will help further individualize lung cancer treatment and may offer new insights into prevention.
An issue that remains uncertain is whether female never-smokers are more likely than male never-smokers to develop lung cancer. A higher rate of lung cancer among female never-smokers has been reported but a recent combined analysis of several previous studies raised some doubts about these findings.7-9 In the combined analysis, the overall frequency of lung cancer was similar among male and female never-smokers. In certain age groups, however, there did appear to be differences in lung cancer incidence rates between men and women: among younger never-smokers, women had higher rates of lung cancer than men, whereas the reverse was true among older never-smokers. This variability by age did not meet the criteria for statistical significance, however, suggesting that it could have occurred by chance alone. A point on which there is more agreement is that female never-smokers have a lower rate of death from lung cancer than male never-smokers.
The Risk of Radon
Radon is a radioactive gas produced by the decay of naturally occurring uranium in soil and water. It has no color, odor, or taste.15 In the United States, radon is the leading cause of lung cancer in nonsmokers and the second-leading cause of lung cancer overall. It is thought to account for 21,000 lung cancer deaths in the United States each year, with 2,900 of those deaths occurring in nonsmokers.13 Worldwide, the World Health Organization estimates that up to 15 percent of lung cancers are caused by radon.16
For most individuals homes are the greatest source of radon exposure. An estimated one in 15 U.S. homes has high levels of radon.13 Within a home radon levels tend to be highest in basements and cellars and other parts of the house that are in contact with the ground. Within a neighborhood radon concentrations can vary greatly from house to house.
The Environmental Protection Agency Issues Health Advisory on Radon to Prevent Lung Cancer
The US Environmental Protection Agency (EPA) has urged Americans to test for radon gas in their homes to prevent lung cancer. In a separate report, researchers from Europe published the latest analysis of the effects of radon in homes and the risk of lung cancer in the February issue of the British Journal of Medicine. The EPA notes that the principal source of radon in homes is likely to be soil gas that is drawn indoors.4,10-13
Radon gas is a term used for the short-lived radioactive disintegration products of the chemically inert gas radon-222. Radon occurs naturally from the decay of uranium-238. Radon affects humans by seeping through the soil and into buildings. Some buildings have a high concentration of radon and others a low concentration and the only way to know is by direct testing. The EPA report suggests that radon can accumulate in homes, especially in the winter months, which is the optimal time they suggest for testing. The EPA report suggests that this is a problem for 1 in 15 homes in the US.4,11
To identify high levels of radon, homeowners should test for radon every two years, or whenever they move, make structural changes to their homes, or occupy a previously unused level of their home. Do-it-yourself radon test kits are available at many hardware stores, and testing can also be performed by a professional. If the test identifies high radon levels (greater than 4 picocuries per liter, steps to reduce radon include increasing ventilation under floors and sealing gaps and cracks in floors. During the construction of new homes, radon-reduction measures can be built into the house from the start.10-13
Cruciferous Vegetables May Reduce Risk of Lung Cancer
According to a study published in Lancet, cruciferous vegetables such as cabbage, broccoli, and brussel sprouts may reduce the risk of lung cancer; the extent of protection appears to vary by genotype.
Understanding DNA Damage Response or DDR and Cancer Treatment
What is DNA Damage Response or DDR?
Studies of diet and lung cancer have consistently reported that eating vegetables-particularly cruciferous vegetables such as cabbage and broccoli-may protect against cancer.
In order to provide additional information about the link between vegetable intake and lung cancer, an international group of researchers assessed whether the anti-lung cancer benefit of eating vegetables varied by a person’s genotype.
Research focused on two genes: GSTM1 and GSTT1. Patients with “null” variants of one or both of these genes have lower levels of glutathione-S-transferase, an enzyme involved in the elimination of isothiocyanates from the body. Because isothiocyanates are thought to be one of the components of vegetables that protect against cancer, people who have less ability to eliminate this compound (as a result of having a null variant of the GSTM1 and/or GSTT1 gene) may derive more of an anticancer effect from vegetables.
The study involved 2141 subjects with lung cancer and a comparison group of 2168 subjects without lung cancer. All patients were enrolled from countries in central and eastern Europe. Information about cruciferous vegetable intake was collected from a questionnaire that asked about cabbage and a combination of brussel sprouts and broccoli.14
Overall, people who ate higher levels of cruciferous vegetables were less likely to develop lung cancer. People who ate cruciferous vegetables at least one a week had a 22% lower risk of lung cancer compared to people who ate cruciferous vegetables less than monthly. As expected, the benefit was particularly apparent among people with the null variant of GSTM1, GSTT1, or both. Among those with the highest vegetable intake, risk of lung cancer was reduced by 33% among people who were GSTM1 null, by 37% among people who were GSTT1 null, and by 72% among those who were both GSTM1 null and GSTT1 null. Among subjects who were not null for either gene, there was no significant link between vegetable intake and lung cancer risk.
The researchers conclude, “These data provide strong evidence for a substantial protective effect of cruciferous vegetable consumption on lung cancer.”
What About Lung Cancer Screening?
For cancers such as breast cancer, colorectal cancer, and cervical cancer, the early detection of disease through the screening of asymptomatic individuals has contributed to decreased rates of death from these cancers. Understandably, there has also been a great deal of interest in whether lung cancer screening scans could reduce lung cancer mortality.
Early detection of lung cancer has proven more difficult. In order for new screening methods to be adopted into routine clinical care, the measures must identify cancer early enough to improve outcomes, must be economically feasible, and must detect cancer with an acceptable degree of accuracy.
Low-dose CT scans are a type of imaging that can identify smaller nodules than chest X-rays, making them a strong candidate for lung cancer screening. Low-dose CT is best used on high-risk individuals (smokers and older individuals, for example because CT scans can have false-positive results, which can lead to unnecessary invasive procedures. In high-risk populations, however, the benefits of screening with low-dose CT scans outweigh the harm and in 2015 the USPSTF made the following recommendations:
- Lung cancer screening should be performed in people age 55 to 80 who have a 30-pack-year or greater history of smoking...
A “pack-year” refers to someone who has smoked an average of one pack of cigarettes per day for a year. Someone who smokes a pack a day will take 30 years to reach 30 pack-years; however, someone who smokes two packs a day will take only 15 years to reach that limit.
- Who are either current smokers, or who have quit in the past 15 years.
The screening should be provided in academic medical centers and other sites with specialized radiologists and surgeons on staff. Under the new guidelines, about 8 million people would be eligible for annual screening. If all of these people complied with screening guidelines, about 4,000 cancer deaths per year could be prevented.
- Crispo A, Brennan P, Jockel KH, et al. The cumulative risk of lung cancer among current, ex- and never smokers in European men. British Journal of Cancer. Advanced online publication August 3, 2004; doi: 10.1038/sjc.bjc6602078.
- US Department of Health and Human Services. The Health Consequences of Smoking: A Report of the Surgeon General. Atlanta: US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health; 2004. Available at: .
- US Department of Health and Human Services. Women and Smoking: A Report of the Surgeon General–2001. Atlanta: US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health; 2001.
- US Environmental Protection Agency. Indoor Air Quality: Radon: Health Risks: Exposure to Radon Causes Lung Cancer in Non-smokers and Smokers Alike. Available at: . Accessed December 27, 2008.
- Pirkle JL, Bernert JT, Caudill SP, Sosnoff CS, Pechacek TF. Trends in the exposure of nonsmokers in the U.S. population to secondhand smoke: 1988-2002*. Environmental Health Perspectives.*2006;114(6):853-58.
- Sun S, Schiller JH, Gazdar AF. Lung cancer in never smokers—a different disease. Nature Reviews. Cancer. 2007;7(10):778-90.
- Wakelee HA, Chang ET, Gomez SL, et al. Lung cancer incidence in never smokers. Journal of Clinical Oncology. 2007;25(5):472-78.
- Freedman ND, Leitzmann MF, Hollenbeck AR, Schatzkin A, Abnet CC. Cigarette smoking and subsequent risk of lung cancer in men and women: Analysis of a prospective cohort study. *Lancet Oncology.*2008;9(7):649-56.
- Thun MJ, Hannan LM, Adams-Campbell LL, et al. Lung cancer occurrence in never-smokers: An analysis of 13 cohorts and 22 cancer registry studies. PLoS Medicine. 2008;5(9):e185.
- Surgeon General Releases National Health Advisory on Radon [press release]. US Department of Health and Human Services. January 13, 2005. Available at: .
- Hill ADD, Auvinen A, Barros-Dios JM, et al. Radon in homes and risk of lung cancer: collaborative analysis of individual data from 13 European case-control studies. British Journal of Medicine . 2005;330:220-225.
- Watts G. Science Commentary: Radon blues. British Journal of Medicine. 2005;330:226-227
- Brennan P, Hsu CC, Moullan N et al. Effect of Cruciferous Vegetables on Lung Cancer in Patients Stratified by Genetic Status: a Mendelian Randomisation Approach. Lancet. 2005;366:1558-60.
- U.S. Preventive Services Task Force Recommends Lung Cancer Screening for High-Risk Populations in Final Statement [news bulletin]. USPSTF website. Available at: . uspreventiveservicestaskforce.org/Page/Name/ newsroom#2013. Accessed October 16, 2015.
- The National Lung Screening Trial Research Team. Reduced lung-cancer mortality with low-dose computed tomographic screening. New EnglandJournal of Medicine. 2011;365:395-409.
- Tammemägi MC, Berg CD, Riley TL, Cunningham CR, Taylor KL. Impact of lung cancer screening results on smoking cessation. Journal of the National Cancer Institute. 2014;106(6):dju084. doi: 10.1093/jnci/dju084.