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Androgen deprivation therapy fails to affect telomere length in prostate cancer

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June 5, 2017

Men with nonmetastatic prostate cancer who received androgen deprivation therapy for 2 years saw no change in leukocyte telomere length when compared with controls who received radiotherapy, according to findings from a case-control study in Australia.

“[Androgen deprivation therapy] is often prescribed for extended times (eg, 3 years for high-risk prostate cancer with curative intent),” Ada S. Cheung, MBBS, FRACP, PhD, of the department of medicine at the University of Melbourne, Australia, and colleagues wrote. “Therefore, these patients offer a unique model of profound and global sex steroid deficiency over an extended period. ... Given that [androgen deprivation therapy] reduces both circulating testosterone and estradiol to near-castrate levels, effects on telomere length — if testosterone indeed plays a role — should be evident irrespective of whether this occurs as a direct effect or via its aromatization to estradiol.”

In a 24-month prospective case-control study, Cheung and colleagues analyzed data from 65 men aged 55 to 85 years with localized, nonmetastatic prostate cancer starting adjuvant androgen deprivation therapy (ADT; n = 40; mean age, 67 years) and 25 controls with prostate cancer (mean age, 71 years) matched for age, BMI, comorbidities, radiotherapy treatment and baseline testosterone level. Men provided fasting blood samples at baseline and 6, 12 and 24 months for serum testosterone and estradiol measurements; leukocyte telomere length, expressed as telomere to single-copy control gene (T/S) ratio, was measured from leukocyte DNA samples. Researchers used generalized linear models to determine the mean adjusted difference between groups during follow-up.

At each time point during follow-up (6, 12 and 24 months), researchers observed no between-group differences in leukocyte telomere length (P = .235 overall). Mean T/S ratio for mean receiving ADT was 1.06 (95% CI, 0.99-1.33), whereas the mean T/S ratio for controls was 0.99 (95% CI, 0.93-1.11).

“In this 2-year prospective case-controlled study, we found no evidence that severe sex steroid deprivation accelerates telomerase shortening in men who have been diagnosed with prostate cancer,” the researchers wrote. “However, large, longer-term studies are required to confirm, or to refute, these findings.” – by Regina Schaffer

Disclosure: The National Health and Medical Research Council of Australia supported this research. The researchers report no relevant financial disclosures.

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