Saturday, October 02, 2010

Swiss chard and lung cancer

If R is you or more specifically your DNA in charge
of cell proliferation, the CH3 or methyl group is your
potential road to ruin.

In the spring of 2008, one of my patients came back from a vacation to Mexico with "pneumonia". But I didn't really think it was pneumonia--the shadow on her x-ray wasn't quite pneumonia-ish, and her symptoms of fatigue and a non-productive cough weren't exactly right either. Anyway, we optimistically tried a course of antibiotics without any change in that infiltrate, and, alas, it was lung cancer after all. Mother of two boys still at home and an ex-smoker for more than a decade, my patient died at home six short months later.

Sometimes rogue DNA--perhaps damaged by aging, smoke, or an errant sunbeam--just gets the best of you despite all that water and veggies and walking at dawn. Still, a person keeps trying to do what she can to avoid the brick wall of mortality, and a recent study in the journal Cancer Research (1) further supports the value of leafy greens. But before we discuss the goodness of greens, a word or two on gene promoter hypermethylation events which are nothing you want occurring in your DNA.

Genes are minute strips of DNA. During a typical 'business-as-usual' day in the life of a normal cell, they are activated by external and internal events and transcribed via RNA to produce worthy proteins that carry on normal activities that include damage repair and control of cell proliferation. If, however, one instructional molecule of the DNA gets permanently tangled up with a methyl group, the entire gene is silenced and its work remains undone. Worse yet, as that cell with its load of methylated DNA replicates itself because no gene product was there to tell it not to, all its offspring cells are also methylated. As a result, an out of control, methylated mass of cells continues to grow unchecked. Sounds like cancer, doesn't it?

So once hypermethylated, can you become demethylated? Such a demethylation process is the dream of scientists looking for chemopreventive strategies. As opposed to chemotherapy drugs which seek and destroy cancer cells, chemopreventive agents act to repair or prevent malignant change. Researchers from the University of New Mexico sorted through sputum from smokers (both current and ex-) seeing if certain dietary strategies were associated with lower levels of methylated genes in expectorated DNA.

Some 1,100 subjects dutifully hawked up their secretions and completed Harvard Food Frequency Questionnaires. As a result, the New Mexican docs were able to identify leafy greens (and we're not talking lettuce here), folate, and multivitamin use as three strategies that correlate with less methyl-generated mess. They proposed that further study might verify these and other agents as ways to reprogram our genome for life without cancer.

Now I'm all for this sort of research as a doctor and an ex-smoker. My problem is that a pile of steamed chard (or kale or greens) is an unappealing mess all its own. Any suggestions of different ways to prepare an appetizing, chemopreventive side dish of greens?
1) Stidley, CA et al. Multivitamins, folate, and green vegetables protect against gene promoter methylation in the aerodigestive tract of smokers. Cancer Res. 2010 Jan 15;70(2):568-74.