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Smoking gun: DNA methylation in prostate cancer


 

FROM CANCER

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More reason, if any is needed, to encourage patients to kick the habit comes from a study showing an association between cigarette smoking and tumor DNA methylation changes.

In a study of tumor tissue from men with prostate cancer (PCa) who underwent radical prostatectomy, smoking was associated with differential methylation across 40 genetic regions, and at least 10 of the regions significantly correlated with levels of messenger RNA (mRNA) expression in corresponding genes.

Brett Mulcahy/ThinkStock

Men whose tumors had the highest levels of smoking-associated methylation were more likely to have higher Gleason grade tumors or regional vs. local stage disease, reported Dr. Irene M. Shui of the Fred Hutchinson Cancer Research Center in Seattle and her colleagues.

“[O]ur results provide support for the hypothesis that smoking-induced changes in DNA methylation may underlie the association of smoking with PCa recurrence and mortality,” they wrote (Cancer 2016 May 3. doi: 10.1002/cncr.30045).

To see whether DNA methylation could at least partly explain the association of smoking with increased PCa progression and mortality, the investigators looked at tumor methylation and long-term follow-up data on 523 patients, 469 of whom (90%) had matched tumor gene expression data available. In all, 43% of the men were never smokers, 47% were former smokers, and 10% were current smokers.

The investigators examined tumor methylation profiles by smoking status, with the goals of determining whether smoking-associated changes in methylation are linked to mRNA expression, and whether they are related to disease prognosis.

They found that 40 DNA methylation regions were associated with smoking, and that 10 of the regions were strongly correlated with mRNA expression. They then used these 10 regions to create a smoking-related methylation score.

As noted before, the score was associated with adverse outcomes, with men in the highest third having an odds ratio (OR) for disease recurrence of 2.29 (P = .0007), and an OR of 4.21 for death from prostate cancer (P = .004)

The associations between smoking-related methylation scores and worse outcomes were slightly less strong but still significant after adjustment for Gleason score and pathologic stage.

“Importantly, there is evidence that smoking-related methylation changes in blood may be reversible; men who quit smoking for longer periods of time have methylation profiles similar to those of never-smokers,” the authors wrote.

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