Scientists say that smoking tobacco is so toxic for the body that it changes the immune system, leaving people vulnerable to more disease and infection even years after they have quit – while other researchers have found that smokers who quit before 50 have 17% less chance of cancer than those who never give up.
Although smoking rates have been declining since the 1960s, it’s still the leading cause of preventable death in the United States, causing more than 480 000 deaths each year, reports CNN.
For decades, the medical profession has been telling smokers that the habit can lead to serious problems like lung cancer, heart attack or stroke, but recent research, published in the journal Nature, offers another reason to quit.
The study shows how smoking decreases the body’s ability to fight off infection immediately and over time, and may also put someone at risk of chronic diseases involving inflammation, like rheumatoid arthritis and lupus.
“Stop smoking as soon as possible,” warned study co-author Dr Violaine Saint-André, a specialist in computational biology at Institut Pasteur in Paris. “The key message of our study, especially to the youth, is that there seems to be a significant interest for long-term immunity to never start smoking.”
The researchers looked over time at blood samples from a group of 1 000 healthy people aged 20 to 69. The group was equally divided between men and women.
The researchers wanted to see how 136 variables, including lifestyle, socio-economic issues and dietary habits – in addition to age, sex and genetics – affected immune response. They exposed the blood samples to common germs like E. coli bacteria and the flu virus and measured the immune response.
Smoking, body mass index and a latent infection caused by the herpes virus had the most impact, with smoking creating the biggest change. It had nearly the same impact on immune response as important factors such as age or sex.
“It’s considerable,” Saint-André said.
When smokers in the study quit, their immune response got better at one level, but it didn’t completely recover for years, said study co-author Dr Darragh Duffy, who leads the Translational Immunology Unit at the Institut Pasteur.
“The good news is, it does begin to reset,” he said. “It’s never a good time to start smoking, but if you’re a smoker, the best time to stop is now.”
The study also found that the more someone smoked, the more it changed their immune response.
“Cutting down any amount is still a good thing in terms of this impact,” Duffy said.
Smoking, the study found, seemed to have long-term epigenetic effects on the immune system’s two major forms of protection: the innate response and the adaptive response. The effect on the innate response quickly goes away when someone stops smoking, but the effect on the adaptive response persists even after they quit.
The innate immune response is the general way the skin, mucous membranes, immune system cells and proteins fight germs. It’s a fast mover, but it’s a blunt instrument.
When the body determines that the innate response isn’t protective enough, the adaptive immune system kicks in. It is made of antibodies in the blood and other bodily fluids, B and T lymphocytes that can “remember” a threat and better target threats it’s seen before.
“The major discovery of our study is that smoking has short-term but also long-term effects on adaptive immunity associated with B cells and regulatory T cells and with epigenetic changes,” Saint-André said.
The new research has some limitations. The experiment was done in blood samples in the lab, but the immune system may react differently in real life. However, human challenge studies are still relatively limited in size compared with what they were able to show with a large collection of blood samples, Duffy said.
Dr Albert Rizzo, chief medical officer of the American Medical Association, said doctors have long known that smoking leads to inflammation in the lung but that doesn’t account for all of the problems with the immune system.
It also seems to explain why even smokers who may have quit could still develop conditions like chronic obstructive pulmonary disease (COPD).
Meanwhile, reinforcing the importance of quitting the habit, a Korean study has confirmed that smokers who give up and stick with it see the greatest reduction in cancer risk.
Smoking cessation was associated with a reduced cancer risk in the long run, particularly when quitting was sustained and occurred prior to middle age, the large population-based study found.
Over a mean 13-year follow-up, smokers who completely quit had a 17% lower risk of any cancer compared with people who continuously smoked (HR 0.83, 95% CI 0.80-0.86), according to findings from Jin-Kyoung Oh, PhD, of the National Cancer Centre in Gyeonggi, Korea, and colleagues, published in JAMA Network.
Medpage Today reports that complete quitters had lower cancer risk when it came to several different tumour types as well:
• Lung cancer: HR 0.58 (95% CI 0.53-0.62)
• Liver cancer: HR 0.73 (95% CI 0.64-0.82)
• Stomach cancer: HR 0.86 (95% CI 0.79-0.93)
• Colorectal cancer: HR 0.80 (95% CI 0.72-0.89)
Though to a lesser degree, some benefit was observed for relapsing and transient quitters, “reaffirming a linear decreasing trend in the order of continuous smokers, relapsed quitters, transient quitters, complete quitters, and never smokers”, the researchers wrote in JAMA Network Open.
Notably, complete quitters had a cancer risk that was slightly higher than that of continuous smokers for the first 10 years after quitting (HR 1.12, 95% CI 1.08-1.16), but the risk decreased sharply when individuals reached 15 years of cessation or more (HR 0.41, 95% CI 0.38-0.44).
“The observed increase in the cancer risk after smoking cessation may be attributed to the inclusion of individuals who had already accumulated substantial damage caused by smoking, known as sick quitters,” the team said.
“This trend aligns with the well-documented phenomenon of escalated medical use and associated expenses among those who have just quit.”
The authors reported that regardless of when a person gave up smoking within their lifetime, their cancer risk was still significantly reduced.
However, when smokers quit before the age of 50, their risk was reduced to a greater degree (HR 0.43, 95% CI 0.35-0.53) than if they quit after 50 (HR 0.61, 95% CI 0.56-0.66).
Neil Schachter, MD, of Mount Sinai Health System in New York City, suggested that the slow development of cancer itself, which requires multiple genetic mutations in the cells affected, may play a role in the long-term divergence of incident cancer rates.
“Somebody who quits at an earlier age probably has – number one – fewer of these damaged DNA segments and also is probably a little bit better equipped to repair them,” he said.
Schachter stressed that among those who have quit, utilising diagnostic tools like CT scans, alongside preventative strategies, was key to hopefully catching cancer in its earlier stages.
“Even in that high-risk period after the first decade when there continues to be an increase in the number of cancers, particularly lung cancer, there is a good chance that if they take advantage of these preventive programmes, that they will come out with a good result,” he said.
For the study, Oh and colleagues relied on data from the National Health Insurance Service in South Korea. Included were people who underwent health screening during the baseline period (years 2002 and 2003) and were followed out to 2017.
Patients who had died or were diagnosed with cancer before 2006 were not included in the analysis, as were those missing certain informational data such as smoking duration, BMI, and income level.
Ultimately, 2 974 820 participants were included in the analysis: 42% were women, and the average age was 49 for women and 43 for men.
Health exams were conducted in two-year examination cycles. Based on the smoking status listed in these reports, patients were categorised as complete quitters, transient quitters (alternating between current and former smoking in the following examination cycles), relapsed quitters, continuous smokers, and never smokers.
Over the mean 13.4 years of follow-up, 196 829 cancer diagnoses were confirmed.
Lung cancer was the first type of cancer to be affected by smoking cessation, decreasing, on average, three years earlier than the other types of cancer analysed, the investigators found.
Researchers excluded people who were past smokers at baseline and only counted years of smoking cessation for those who quit smoking during the study period.
“Considering that older people who quit smoking are more likely to have a longer duration of smoking cessation, it is important to address this confounding effect, particularly in studies involving participants spanning various age ranges,” Oh’s group wrote.
Nevertheless, the researchers did explain that selection bias may have been introduced to the study, as analysis required “consecutive examinations of biennial health screens” as a way to determine smoking status on a consistent basis.
Study 1 details
Smoking changes adaptive immunity with persistent effects
Violaine Saint-André, Bruno Charbit, Darragh Duffy & The Milieu Intérieur Consortium, et al.
Published in Nature on 14 February 2024
Abstract
Individuals differ widely in their immune responses, with age, sex and genetic factors having major roles in this inherent variability. However, the variables that drive such differences in cytokine secretion – a crucial component of the host response to immune challenges – remain poorly defined. Here we investigated 136 variables and identified smoking, cytomegalovirus latent infection and body mass index as major contributors to variability in cytokine response, with effects of comparable magnitudes with age, sex and genetics. We find that smoking influences both innate and adaptive immune responses.
Notably, its effect on innate responses is quickly lost after smoking cessation and is specifically associated with plasma levels of CEACAM6, whereas its effect on adaptive responses persists long after individuals quit smoking and is associated with epigenetic memory. This is supported by the association of the past smoking effect on cytokine responses with DNA methylation at specific signal trans-activators and regulators of metabolism. Our findings identify three novel variables associated with cytokine secretion variability and reveal roles for smoking in the short- and long-term regulation of immune responses. These results have potential clinical implications for the risk of developing infections, cancers or autoimmune diseases.
Study 2 details
Cancer Risk Following Smoking Cessation in Korea
Eunjung Park, Hee-Yeon Kang, Min Kyung Lim, et al.
Published in JAMA Network Open on 2 February 2024
Abstract
Importance
Tobacco smoking is associated with increased risk of various cancers, and smoking cessation has been associated with reduced cancer risks, but it is still unclear how many years of smoking cessation are required to significantly reduce the cancer risk. Therefore, investigating the association of smoking cessation with cancer is essential.
Objective
To investigate the time course of cancer risk according to the time elapsed since smoking cessation and the benefits of smoking cessation according to the age at quitting.
Design, Setting, and Participants
This population-based, retrospective cohort study included Korean participants aged 30 years and older who underwent 2 or more consecutive health examinations under the National Health Insurance Service since 2002 and were followed-up until 2019. Data analysis was performed from April to September 2023.
Exposures
Exposures included (1) time-updated smoking status based on biennial changes in smoking status, defined as complete quitters, transient quitters, relapsed quitters, continuous smokers, and never smokers; (2) duration of smoking cessation, defined as years since quitting; and (3) categorical variable for age at quitting.
Main Outcomes and Measures
The primary cancer was ascertained using the cancer registry data: all-site cancer (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10] codes C00-43, C45-96, or D45-D47), lung cancer (ICD-10 code C34), liver cancer (ICD-10 code C22), stomach cancer (ICD-10 code C16), and colorectal cancer (ICD-10 codes C18-20). Hazard ratios (HRs) and 95% CIs were estimated using a Cox proportional hazards regression model with follow-up years as the timescale.
Results
Of the 2 974 820 participants, 1 727 340 (58.1%) were men (mean [SD] age, 43.1 [10.0] years), and 1 247 480 (41.9%) were women (mean [SD] age, 48.5 [9.9] years). Over a mean (SD) follow-up of 13.4 (0.1) years, 196 829 cancer cases were confirmed. Compared with continuous smokers, complete quitters had a lower risk of cancer, with HRs of 0.83 (95% CI, 0.80-0.86) for all cancer sites, 0.58 (95% CI, 0.53-0.62) for lung, 0.73 (95% CI, 0.64-0.82) for liver, 0.86 (95% CI, 0.79-0.93) for stomach, and 0.80 (95% CI, 0.72-0.89) for colorectum. The cancer risk exhibited a slightly higher value for 10 years after quitting compared with continued smoking and then it decreased over time, reaching 50% of the risk associated with continued smoking after 15 or more years. Lung cancer risk decreased 3 years earlier than that of other cancer types, with a larger relative reduction.
Regardless of quitting age, a significant reduction in the cancer risk was observed. Quitting before the age of 50 years was associated with a greater reduction in lung cancer risk (HR, 0.43; 95% CI, 0.35-0.53) compared with quitting at age 50 years or later (HR, 0.61; 95% CI, 0.56-0.66).
Conclusions and Relevance
In this population-based retrospective cohort study, sustained smoking cessation was associated with significantly reduced risk of cancer after 10 years since quitting. Quitting at any age helped reduce the cancer risk, and especially for lung cancer, early cessation before middle age exhibited a substantial risk reduction.
Nature article – Smoking changes adaptive immunity with persistent effects (Open access)
JAMA Network Open article – Cancer Risk Following Smoking Cessation in Korea (Open access)
CNN article – Smoking’s effects on the immune system can last years, study finds (Open access)
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