Wednesday, May 28, 2008

Genetic Susceptibility to Cancer

I love the pen. It has the ability to befuddle, convince, coerce, and give false or true hope. This is the case with journal articles. I am always amazed by what is reported and what is real. You see, the Buddhists will tell you that all reality is merely false. Why? Because perception is what we view to be reality. Since reality needs to be constant, yet perception not only changes but is viewer is not constant. Hence, there is no spoon.

This is the case with a recent article published in JAMA's clinician's corner. The article entitled "Genetic Susceptibility to Cancer" did something wonderful. It took 161 meta and pooled analyses encompassing 18 cancer sites and 99 genes/344 variants (Trust me, this took some heavy lifting) and evaluated for Odds Ratios and evaluated statistical significance. They then evaluated the false positive report probability (this is very important when trying to decide which genes are noteworthy/FPRP) Most evaluated polymorphisms were from either metabolizing genes or DNA repair genes. Big surprise, especially given Knudson's 2 hit hypothesis. (2 mutations to cause a cancer, thus if you can process the toxin quicker than it can cause damage or if you can fix the damager quicker than it causing cancer, You Win. Or Vice Versa)

So what did they find and what did they list in their abstract?

Findings: 13 of the 344 variants had OR >1.5, Only 4 IMHO were noteworthy (OR 2.0 or FPRP<0.2)>

Reported in abstract: "....nearly one-third of gene variant cancer associations were statistically significant, with variants in genes encoding for metabolizing enzymes among the most consistent and highly significant"

See how my bolding made it seem more important? That is the problem here. All this study let me know is that most gene studies involving linkage and cancer are not significant. But the busy clinician reads this as the bold. Not that there are only 3 Linkages worth a hoot with OR of at least 1.5

Those associations ARE: NAT2 slow acetylator and bladder cancer, MTHFR C677T and gastric cancer, lastly GSTM1 null allele and bladder cancer. This makes sense, especially given the fact that these cancers have been linked to environmental exposures....

The Sherpa Says:

Abstracts are misleading. To fully report on these articles one must really read the article. How does the busy clinician or journalist have time for that? The Sherpa is even finding it hard! As for Senator Kennedy, that cancer is likely genetic. IMHO

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