|Part I||Part II||Part III|
|The Connection Between Smoking and Prostate Cancer||Smoking and Your Telomeres||Smoking and Race|
Telomeres are like aglets, the little plastic tips on the ends of shoelaces (in fact, their name comes from the Greek words meaning “end” and “part”). They are tiny regions of repeated DNA sequences that cap the ends of chromosomes and help protect them from deteriorating. Just as an aglet doesn’t last forever – and then your shoelace gets frayed on one end and is hard to lace up – telomeres wear out, too. They shrink a little bit every time a cell divides.
When a telomere gets too short, the chromosome it’s supposed to safeguard – like the poor shoelace – loses its stability, and mutations can result. Eventually, repeated hits to the chromosome can lead to cancer. “Cancer cells tend to have much shorter telomeres than normal cells from the same tissue,” notes Platz. “The shorter the telomere, the more unstable the chromosome.”
The most dangerous cancers – the ones that metastasize – are those with the most unstable chromosomes. This fact led Platz, several years ago, with Alan Meeker, Ph.D., Angelo De Marzo, M.D., Ph.D., and other colleagues at Hopkins and Harvard, to wonder whether the length of telomeres – in cancer cells, or even in normal cells that may be headed for cancer – might foretell how aggressive a man’s prostate cancer is likely to be. They investigated the link between the length of telomeres and the risk of highly aggressive disease in 596 men with clinically localized prostate cancer who underwent radical prostatectomy; the men were participants in a massive, long-term investigation called the Health Professionals Follow-up Study. Of these men, 46 died of prostate cancer. The team calculated the typical length of the telomeres in the prostate tissue, looked at the variation in telomere length from cell to cell, and then correlated all this with the men’s risk of dying of their prostate cancer over the next 10 years after their surgery. They took into account each man’s pathologic stage of cancer and Gleason score, as well.
“We found that men with more variable telomere length in their prostate cancer cells had a 2.4-times-higher risk of dying of their prostate cancer,” says Platz, regarding the Hopkins study. “We also found that men with shorter telomeres in their nearby stromal (connective tissue) cells had a 4.2-times-higher risk of dying.” Putting these two findings together, they found that men who had more variable telomere length in their prostate cancer cells, and shorter telomeres in their stromal cells were 14 times more likely to die of their prostate cancer. All of these findings were independent of currently used prognostic factors like stage and grade. “Equally important, we found that men who did not have this combination rarely died of their prostate cancer over the 10 years.” This study was led by PCF Young Investigator Christopher Heaphy, Ph.D., and published in the journal, Cancer Discovery.
How does smoking factor into this equation? To find out, PCF Young Investigator Corinne Joshu, Ph.D., M.P.H. ,along with Platz and the Hopkins and Harvard colleagues recently looked at the link between smoking and telomere length in 567 men using the data from the Health Professionals Follow-Up Study. Their findings were published in the journal, Prostate. Among men without other health problems, “we found that current smokers and men who quit less than 10 years ago had the most variable telomere length in stromal cells and in cancer cells, and concluded that telomere variability in prostate cells may be one way that smoking influences poor prostate cancer outcomes.”
Remember this phrase: current smokers.