The Sins of Our Grandfathers

Posted by Samantha Powell on June 21st, 2013 |

By Tim Spector, Professor of Genetic Epidemiology, King’s College London / June 21, 2013

A special report by the New Scientist recently caught my eye. The report by Linda Geddes on June 30, 2012 claims that lung cancer is on the rise and focuses on the difficulties of getting funding for an illness that most people view negatively because of its association with smoking.

The incidence of lung cancer seems to be on the increase, and it is by far one of the biggest killer cancers worldwide. The general perception not only by the general public but by the medical community is that of lung cancer as a direct consequence of smoking and therefore largely caused by personal lifestyle decisions. However, a recent trend is emerging whereby many patients afflicted with lung cancer have no history of smoking. Furthermore, although the outcomes are still poor, it seems that these ‘blameless’ patients have a better survival rate with a better response to new medications than those who report a history of smoking. Mutations in the EGFR and ALK genes are the classical feature of these types of cancers whilst smokers seem to also show mutations on a third gene, KRAS which may make it tougher to treat.

How can an illness traditionally associated with smokers or due to passive smoking (due to you inhaling other family members cigarettes) be increasingly affecting individuals without any smoking history? Could epigenetics explain some of this phenomenon?

As our society is now very aware of the health consequences of smoking, the rate of persistent smoking has dropped steadily in the west in the last few decades. Twenty-one percent of UK adults smoke compared to 39 percent in 1980. However most of us are children or grandchildren of smokers who lived at a time before the real dangers associated with this habit were known. Both my parents — one a doctor and the other a physio smoked — my mother heavily for 30 years. I still remember the fume-filled seven hour car journeys with dread. On the whole smoking in the 1950s and 60s was an inoffensive fashionable past time as well observed in the TV series Mad Men. In the case of males this marked the transition into adulthood and success and for women their independence from traditional feminine roles.

Epigenetic processes that lead to some of our natural cancer protective genes being turned off could explain these increases in lung cancer. A study recently showed that smokers after a few years methylated and so turned off a key tumour suppressor, gene P16, important in many cancers (Ma et al 2011). This may explain how the consequences of bad habits from past generations are being visited upon us even though we may have adopted a squeaky clean lifestyle. The epigenetic signals on the DNA caused by smoking could be passed on directly when we are children via passive smoking or possibly passed down through inherited epigenetic marks from our parents and grandparents. Cross-generational transmission in humans is still controversial as unlike in animals where there are now many studies — there are so few good equivalent examples. One study of Bristol children showed differences in growth depending on whether their grandfather smoked before the age of eleven- suggesting such transmission is possible.

So if this fills you with gloom and doom, remember that epigenetic changes are potentially reversible — a recent study we performed showed that three months after quitting smoking, many epigenetic changes had reverted. But if you are a non smoker rather than just blaming your grandparents, let’s pursue epigenetic antidotes and hope more drugs become available soon.


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