'If dad-to-be smokes DNA damage may pass to kids'

First published in Health News by

If you want help to stop smoking, contact your GP or local NHS stop services. For more information visit NHS Smokefree or call 0800 022 4332.

“Fathers who smoke pass on damaged DNA to their children – raising the risk of cancer,” the Daily Mail has warned.

The Mail’s story was based on a small study of predominantly Greek families, whose lifestyle and genetic make-up were analysed to detect whether parental smoking before and during pregnancy led to DNA damage in their newborn babies.

Mothers smoking during pregnancy and fathers smoking before pregnancy were the two most relevant factors to predicting the level of genetic damage in the newborn.

The Mail’s suggestion that this DNA damage could increase the child’s risk of cancer is slightly misleading. This study did not investigate whether the DNA damage had any effect on the infants’ cancer risk, or their risk of any other disease.

Smoking during pregnancy is already known to harm the unborn child. This study suggests that fathers who smoke regularly before conception may also damage their children (at a genetic level), but stops short of proving this or demonstrating how paternal smoking may affect the health of the infant.

 

Where did the story come from?

The study was carried out by a collaboration of international researchers led by a team at the University of Bradford. The work was funded by the European Union Integrated Project NewGeneris and the study was published in the peer-reviewed Journal of the Federation of American Societies for Experimental Biology.

The researchers wanted to investigate the possible roles of exposure to environmental and lifestyle toxins (such as tobacco smoke) before and during conception and pregnancy. They wanted to see how these might affect the DNA of newborn babies. However, this study did not investigate whether the DNA damage had any effect on the infants’ cancer risk, or their risk of any other disease. Similarly, the proposed link between fathers smoking and DNA damage to their children needs further investigation before we can be sure such a link exists.

 

What kind of research was this?

This was a cohort study that examined the blood of mothers and their babies as well as the blood and sperm of the babies’ fathers to see whether genetic damage was passed on from either parent to the newborn and which, if any, lifestyle factors were associated with this inherited damage.

A cohort study is an appropriate way to investigate this phenomenon. It means you can be certain that the lifestyle and environmental exposures came before the pregnancy. However, it is difficult to prove cause and effect with this type of study because the role of genetics and environmental exposure is difficult to disentangle.

 

What did the research involve?

Blood and semen samples from the parents of newborns were analysed to see whether genetic damage present in the parental DNA was inherited by the infant. The researchers examined to what extent this parental DNA damage was linked to environmental toxins such as tobacco smoke.

All 39 participating families answered a structured questionnaire, which was used along with medical records to obtain data on:

  • pre-pregnancy body mass index (BMI)
  • age
  • occupation
  • ethnicity
  • lifestyle during pregnancy (smoking habits, alcohol intake, environmental tobacco smoke exposure and supplement intake)
  • delivery type
  • newborn length and head circumference
  • birth weight
  • newborn gender
  • gestational age

Smoking exposure was measured by detecting cotinine levels in the blood. Cotinine is a chemical that results from the breakdown of nicotine in the body. The levels of cotinine in the blood are proportional to the level of smoke exposure (either direct exposure or from second-hand smoke).

The researchers obtained umbilical-cord blood from 39 newborns and peripheral blood from their mothers from a hospital in Bradford (15) and the University of Crete medical school (24). Blood samples were taken from all fathers of the newborns, while semen samples were obtained from 15 fathers. The men’s sperm DNA was also analysed for DNA damage.

Researchers isolated and examined DNA from the sperm, as well as lymphocytes (cells) from the blood samples. They looked at a specific section of DNA, called the “γH2AX foci”, to look for DNA damage including single and double strand breaks. Any damage to this gene would affect the amount of  protein that this particular gene produced. The researchers looked at the level of this protein in the cells from the blood samples.

The analysis sought to detect differences in the maternal, paternal and newborn characteristics (such as smoking and alcohol) that predicted the level of DNA damage in the newborn baby.

A sub-group of 23 families was analysed to compare DNA damage in three groups:

  • In 10 families, the mother was a non-smoker and not exposed to second-hand smoke, while the father did not smoke.
  • In four families, the mother was a non-smoker and not exposed to second-hand smoke, but the father smoked.
  • In nine families, the mother and father both smoked.

 

What were the basic results?

The average age of the mothers was 29.1 (ranging from 18 to 40) while the dads' average age was 32.9 (ranging from 21 to 43). The majority of the parents were Caucasian and lived in Crete, Greece. A fifth of all the women (20.7%) drank alcohol during their pregnancy, while 33.3% actively smoked during the same time.

Both maternal smoking during pregnancy and paternal smoking at the time of conception were significant predictors of DNA damage at the γH2AX foci in newborns. However, using results from the subgroup analysis, the researchers showed that maternal second-hand smoke exposure was not associated with DNA damage in the newborn’s blood.

 

How did the researchers interpret the results?

The study authors said that their findings “reveal a role for cigarette smoking in the induction of DNA alternations” in human offspring and that the effect of paternal smoking “may be transmitted” via the DNA of the father’s sperm.

 

Conclusion

This small study on 39 newborns and their parents found that maternal smoking during pregnancy, along with paternal smoking before pregnancy, predicted the amount of DNA damage in the cord blood of the newborn infants at a specific section called the “γH2AX foci”.

This study is important because it highlights the potential harmful effect of maternal and paternal smoking before and during pregnancy, but falls short of proving that paternal smoking caused damage to the infant.

While the findings may add weight to the warnings against smoking, it is worth bearing in mind the limitations of this study before concluding that men who smoke before conception damage their children’s health. These limitations included:

Sample size and lack of diversity

The study was very small and looked at mainly Greek parents. It is unclear whether the same associations would be found in a larger, more diverse study population. Larger cohort studies could address this weakness.

No examination of the effect of DNA damage

The effect of the γH2AX foci DNA mutation on the health of the infants was not assessed. It is unclear whether this DNA-level damage contributed to any short- or long-term illness in the infants in the present or in later life.

No evidence of how smoking damages sperm DNA

The biological mechanism leading to genetic changes in the father’s offspring as a result of him smoking is not shown by this study. The researchers suggested it is likely to be channelled through the DNA in the sperm.

DNA damage could have been caused by other factors

It was unclear as to what extent smoking was responsible for the genetic damage found in men’s blood and sperm or the genetic changes then found in the infants. There may be other environmental factors, not assessed in this study, which caused the damage. Larger studies, tightly controlling the role of other factors influencing a father’s sperm DNA, are needed to further clarify which factors are most important.

Smoking is harmful in many varied ways and smoking during pregnancy is particularly ill-advised as it can harm the unborn child. However, this study suggests that fathers who smoke regularly before conception may also cause genetic-level damage to their children, but stops short of proving this.

If you want help to stop smoking, contact your GP or local NHS stop services direct. For more information visit NHS Smokefree or call 0800 022 4332.

 

Analysis by Bazian. Edited by NHS Choices.

Laubenthal J, Zlobinskaya O, Poterlowicz K et al. Cigarette smoke-induced transgenerational alterations in genome stability in cord blood of human F1 offspring. FASEB Journal. Published online June 22 2012

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