Smoking and Epigenetics: How Cigarettes Change Your DNA
Quick answer: Smoking changes DNA methylation — chemical tags that help switch genes on and off — at thousands of sites. In the largest study, of nearly 16,000 people, most of these changes in blood returned toward never-smoker levels within five years of quitting, while a small number, including the AHRR gene, were still different 30 years on.
Most people know that smoke carcinogens damage DNA and cause mutations. Smoking also changes how genes are regulated, without changing the DNA sequence. Researchers are still working out what these changes mean for health, but they have learned a good deal about how many there are and how far they recover.
What Epigenetics Is
Your genome (DNA sequence) is largely the same in every cell in your body. What makes a lung cell different from a liver cell is not the DNA, but which genes are turned on or off — and how actively they're expressed. This regulation is partly controlled by epigenetic marks: chemical modifications to DNA or the histone proteins around which DNA is wrapped.
The most studied epigenetic mechanism is DNA methylation: the addition of a methyl group (CH3) to a cytosine base in the DNA, typically at CpG sites (where cytosine is followed by guanine). Methylation generally reduces gene expression.
Key points:
- Epigenetic marks are heritable (passed to daughter cells during cell division)
- They can be modified by environment, diet, chemical exposure, and lifestyle
- Some marks are more reversible than others
How Smoking Changes DNA Methylation
Researchers think smoke chemicals, including tar compounds (PAHs) and reactive oxygen species, change methylation both by damaging DNA and by setting off the cell's defences against those chemicals. The exact routes are still being worked out.
The largest study so far pooled blood samples from 15,907 people in 16 cohorts. Comparing current smokers with never-smokers, it found 2,623 CpG sites, linked to 1,405 genes, where methylation differed. Those genes were over-represented among genes already linked with lung function, cancers, inflammatory diseases and heart disease. Note that these are blood samples; lung and other tissues may differ.
Key Genes Affected
AHRR (aryl hydrocarbon receptor repressor) is the most consistent finding. One site in this gene is among the strongest smoking signals in most studies, and its methylation is being studied as a marker of tobacco exposure. AHRR helps control the cell's response to PAHs, the tar compounds in smoke.
Other genes that turn up again and again include F2RL3 (a receptor on blood platelets), GPR15 (an immune-cell receptor) and LRRN3. For most of these genes, what the methylation change does to health is not yet known. Studies of lung tumours also find cancer-related genes silenced by methylation, but tumour findings can't be read as effects on healthy smokers' blood.
After Quitting: What Recovers and What Doesn't
This is the part that matters most for former smokers. In the same large study, researchers followed Framingham Heart Study participants with up to 30 years of smoking records:
- Most sites recover. Methylation at most of the smoking-linked sites returned toward never-smoker levels within five years of quitting.
- Some persist. 36 sites in 19 genes — including AHRR and F2RL3 — had not returned to never-smoker levels even 30 years after quitting.
The authors point out that the fast recovery of most sites fits the fact that risks of many smoking-related diseases fall quickly after quitting, while the persistent sites might help explain risks that linger. That link is a hypothesis. What is clear from the disease data is that quitting lowers risk at any age, and the sooner you stop, the less has built up. For how different kinds of damage recover, see the smoking damage timeline.
Implications for Children of Smokers
A meta-analysis of 13 cohorts and 6,685 newborns found that smoking in pregnancy was linked with methylation differences at over 6,000 sites in the baby's blood, some in genes relevant to conditions that maternal smoking can cause, such as orofacial clefts and asthma. In older children, the same sites still showed differences. Whether these marks cause health problems, or only record the exposure, is still being studied.
The practical point is the same one the NHS makes: stopping smoking in pregnancy protects your baby, and free support is available through your midwife.
References
- Joehanes R et al. "Epigenetic signatures of cigarette smoking." Circ Cardiovasc Genet, 2016. PubMed · Full text
- Zeilinger S et al. "Tobacco smoking leads to extensive genome-wide changes in DNA methylation." PLoS One, 2013. PubMed
- Joubert BR et al. "DNA methylation in newborns and maternal smoking in pregnancy: genome-wide consortium meta-analysis." Am J Hum Genet, 2016. PubMed
Frequently Asked Questions
Can smoking permanently change your DNA?
Smoke carcinogens cause mutations — changes to the DNA sequence — that can build up over years. Methylation changes are different: in a large study, most smoking-linked methylation sites in blood returned toward never-smoker levels within five years of quitting, though a few, including AHRR, were still different after 30 years.
Do epigenetic changes from smoking affect your children?
Smoking in pregnancy is linked with methylation differences at thousands of sites in newborns' blood, and some are still seen in older children. Passing marks on through sperm or eggs is much less established in humans. Stopping smoking in pregnancy is one of the best things you can do for your baby, and your midwife can refer you to free support.
How long until epigenetic markers normalize after quitting?
In the largest study so far, most smoking-linked sites in blood returned toward never-smoker levels within about five years. A minority, including sites in AHRR and F2RL3, had not returned after 30 years.
Is there any way to reverse epigenetic damage from smoking?
No treatment is known to reverse smoking-related methylation changes. Quitting is what lets most of them recover, and the sooner you quit, the better.