Sunday, 25 July 2010

Will you get cancer?

Have you ever wondered how some people who smoke heavily all their lives never get lung cancer, yet someone who never smokes (except passively maybe) does?

Firstly, we've all been saturated with food and drink advertisements that boast they contain this and that anti-oxidant, but what about the oxidant that we're being told to be so "anti" about?  Well, "oxidative" stress relates to damaging reactive oxygen species (ROS), which can, amongst other things, cause mutations in your DNA that ultimately lead to carcinogenesis.   Smoking cigarettes increases the amount of ROS in the body - hence the well known fact that smoking is linked to lung cancer.  Check out the video below (straight from YouTube) to help you visualise oxidation and how anti-oxidants work.

So, again, why then do some people suffer from lung cancer when others don't?

One explanation may lie with the activity of the verbosely named enzyme "8-oxoguanine DNA glycosylase", or OGG for short.  OGG acts to repair damaged DNA by removing the most common mutagenic base byproduct, 7,8-dihydro-8-oxoguanine, caused by the oxidative damage of guanine (one of the four bases that make up your DNA and RNA).  A potentially significant relationship has been found between OGG activity and the prevalence of lung, head and neck and also colorectal cancers and adenomas.  Accordingly, individuals who developed lung cancer demonstrated lower OGG activity than controls who did not, noting particularly that the link to lung cancer was not cigarette smoking alone.  In fact, non-smokers with low OGG activity were of a similar risk to developing lung cancer as smokers with high OGG activity, however, those individuals at the greatest risk were smokers with low OGG activity.

Interestingly, when comparisons of OGG activity were made between "at diagnosis" of head and neck cancer and "at post-successful treatment", it was found that the activity remained at an approximate constant level.  This suggests that in head and neck cancer, OGG activity is not an effect of the cancer.  Opposingly, however, OGG has been found to actually increase in colorectal cancers, which must suggest that OGG activity is not a constant in all cancers, but sometimes upregulated, perhaps in a vain attempt to reduce tumour advancement.

Variations in the OGG activity, known as the phenotype (observable physical or biochemical outcome), are considered to be related to the individuals genotype (genetic makeup) based on the three possible combinations of Ser326 and Cys326 allele pairing.  The effects of just two alleles combine to create a phenotype and studies, investigating cancer of the larynx and lung, have found the Ser326 allele to correlate with higher OGG activity when compared to the Cys326 variant. These studies also describe how the allele combinations of Ser/Cys and Cys/Cys are significantly linked to increased risk of developing cancer, particularly amongst heavy smokers and moderate to heavy alcohol drinkers, but do not change the risks for former to moderate smokers/alcohol drinkers.  With this in mind, therefore, it is believed that studying the OGG activity itself is more effective than genotyping because it measures the true effect in vivo.  The significance of the Ser/Cys genotypic combinations must not, however, be disparaged.

I've been searching for details on whether the OGG activity test is actually available now either on the NHS or privately, but have not been able to find any.  I'm guessing that if it is not, there are probably some continuing NHS financial issues preventing it's implementation or some big-wig is refusing to give it the time of day.

Why is this test not out there?

This test marks the way forward to preventing, not treating cancer; a paradigm for future tests for other cancers that can predict predisposition on a bespoke, personal level.  Do you not think it would be comforting to know you had a Ser/Ser combination of alleles?  Alternatively, imagine knowing you were definitely in the "high risk" group for developing lung cancer, would you be put off smoking then (if not intuitively already, of course)?  Anti-smoking campaigns are not enough, we need to make it personal for the individual because everybody if different!!

Your body may be trying to tell you something.  Wouldn't you like to know?

Other useful and informative links:

When the proposal of the OGG test hit the news:

For the NHS's take on the evidence:

For a detailed description of how OGG activity is measured: (if you are unable to access the full paper, email me at and I will happily send you the pdf file)

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