健康習慣與前列腺癌者的端粒較長有關


  【24drs.com】線上登載於The Lancet Oncology期刊的小型先驅研究結果認為,一種綜合型生活型態介入方式可幫助前列腺癌病患的牙齒和端粒存活較久。
  
  加州預防醫學研究院主任Dean Ornish醫師等人報告指出,切片證實為低風險前列腺癌的35名男性,選擇主動監測、全面的生活方式介入,包括飲食、活動、壓力處置、以及支持療法,相較於對照組的端粒長度損失,介入組在5年時的端粒長度較長。
  
  端粒是線性染色體末端的DNA和蛋白質複合物,已被證明對細胞的健康至關重要;端粒縮短與進行過根除式前列腺切除術患者復發前列腺癌風險增加有關,理論上,維持端粒並延長長度與健康較佳以及存活較久有關。
  
  Ornish醫師表示,這是第一篇以控制型研究證明介入方式可以延長人類端粒長度的研究,但它不是在真空狀態中。其他橫斷面研究顯示,處於長期情緒壓力下的人,端粒會比較短,且與面對的壓力程度有正相關,馬拉松跑者的端粒長度也比一般人長。
  
  介入組包括了10名參與「GEMINAL (Gene Expression Modulation by Intervention with Nutrition and Lifestyle)」研究的男性,這些人吃低脂、精製碳水化合物飲食且富含蔬果,每週至少6天有氧運動至少30分鐘,參與壓力處置課程,參加每週1小時的支持團體;至於對照組則只有接受運動監測。
  
  研究者探討週邊血液單核球細胞的端粒長度,測量相對於對照組DNA的端粒長度,測量結果以端粒對單一基因的比率值(T/S)呈現。
  
  5年時,生活型態介入組的男性,相對端粒長度比開始時增加之中位數值為0.06 T/S (四分位距[IQR]為 -0.05 至 0.11);相對的,對照組的端粒縮短,中位數為 -0.03 T/S (IQR,-0.05至 0.03),這個差異達顯著程度( P = .03)。
  
  合併介入組和對照組資料、校正年紀和追蹤長度的雙變項分析,也顯示生活型態改變與端粒長度有關,生活型態改變遵從度每增加1%,則T/S值相對增加0.07(P = .005)。
  
  Ornish醫師等人寫道,我們的發現具有生物學合理性,且與以前的研究一致。然而,鑑於樣本量小,而且這是一個先驅研究,我們報告指出關聯性增加,但未證明因果關係。此外,雖然端粒相對長度增加被視為是有利的,仍須以大型的隨機控制試驗確認完整的生物學影響。
  
  費城賓州大學Perelman醫學院流行病學教授Timothy Rebbeck博士表示,令人鼓舞的是這個介入型研究類型,研究本質上雖是個小樣本研究,但可看出端粒長度的這些差異。
  
  Rebbeck博士未參與此次研究,他指出確認影響機轉是相當困難的,因為端粒長度維持和縮短的生物學相當複雜,包括端粒酵素和各種組合的多種蛋白質。
  
  他指出,眾所周知,壓力、吸菸以及各種不利環境會使端粒縮短,我們真的不知道究竟是怎麼一回事;他也建議研究者採用比T/S值更好的其他測量端粒長度和功能的方法。
  
  Rebbeck博士表示,T/S值是測量整體端粒長度的方法,但是,個別染色體上的個別端粒可能會縮短或延長,縮小測量範圍或許可幫助我們更瞭解實際發生的改變。
  
  Ornish醫師表示,他們的研究團隊希望追蹤這些人更久,觀察端粒長度和疾病惡化之間是否有關聯。
  
  資料來源:http://www.24drs.com/professional/list/content.asp?x_idno=7012&x_classno=0&x_chkdelpoint=Y
  

Healthy Habits Linked to Longer Telomeres in Prostate Cancer

By Neil Osterweil
Medscape Medical News

A comprehensive lifestyle intervention might help prostate cancer patients live to be longer in the tooth and in the telomere, suggest results of a very small pilot study reported online in The Lancet Oncology.

Among 35 men with biopsy-proven, low-risk prostate cancer who opted for active surveillance, a comprehensive lifestyle intervention including diet, activity, stress management, and support was associated with lengthening of telomeres over 5 years compared with a loss of telomere length among controls, report Dean Ornish MD, director of the Preventive Medicine Research Institute, in Sausalito, California, and colleagues.

Telomeres, complexes of DNA and proteins at the end of linear chromosomes, have been shown to be essential for cellular health. Telomere shortening has been associated with increased risk for prostate cancer recurrence in patients who have undergone radical prostatectomy, and it's theorized that telomere maintenance and lengthening may be associated with better health and longer life.

"This study is the first controlled study to show that any intervention may lengthen telomeres in humans, but it's not in a vacuum," Dr. Ornish said in an interview with Medscape Medical News. "There are other, cross-sectional studies showing that people who are under chronic emotional stress tend to have shorter telomeres in direct proportion to the amount of stress they have, or that people who are marathon runners tend to have longer telomeres than those who aren't."

The active intervention group included 10 men who were participants in the GEMINAL (Gene Expression Modulation by Intervention with Nutrition and Lifestyle) study. The participants ate a diet low in fat and refined carbohydrates and high in whole fruits and vegetables; exercised aerobically for at least 30 minutes 6 days each week; engaged in stress management programs; and took part in a 1-hour weekly support group. Controls were followed with active surveillance only.

The investigators looked at telomere length in peripheral blood mononuclear cells, measured as the length of telomeres relative to standard reference DNA. The measure is expressed as a telomere to single-copy gene ratio (T/S).

Over 5 years, men in the lifestyle intervention group had an increase in relative telomere length over baseline of a median 0.06 T/S (interquartile range [IQR], -0.05 to 0.11). In contrast, controls had telomere shortening, by a median of -0.03 T/S (IQR, -0.05 to 0.03), and this difference was significant ( P = .03).

A bivariate analysis of combined intervention and control-group data adjusted for age and length of follow-up also showed an association between lifestyle changes and telomere length, with each percentage-point increase in adherence to lifestyle changes translating into a 0.07 increase in T/S (P = .005).

"Our findings are biologically plausible and consistent with earlier studies. Nevertheless, in view of the small sample size and this being a pilot study, we report increases as associations without necessarily proving causation. Additionally, although increases in relative telomere length are thought to be beneficial, the full biological implications remain to be determined in large randomized, controlled trials," Dr. Ornish and colleagues write.

Encouraging Results

"I think that it's really encouraging that an intervention study of this type, which is by nature going to have a small sample size, could show these differences in telomere length," said Timothy Rebbeck, PhD, professor of epidemiology at Perelman School of Medicine at the University of Pennsylvania, in Philadelphia.

Dr. Rebbeck, who was not involved in the study, notes that determining the mechanism of the effect may be very difficult, because the biology of telomere length maintenance and shortening is highly complex, involving the telomerase enzyme and multiple proteins in various combinations.

"It's well known that stress, smoking, and various kinds of unfavorable environments cause telomeres to shorten, and we really don't know exactly what that is all about," he said.

He also commented that investigators would be wise going forward to employ other methods for measuring telomere length and function in addition to the T/S ratio used in the study.

"The T/S ratio is sort of an overall measure of telomere length, but there might be individual telomeres on individual chromosomes that might be shortening or lengthening, and narrowing that mechanism down might help us understand better what is happening," Dr, Rebbeck said.

Dr. Ornish saidthat his group hopes to follow the men over time to see whether there is a correlation between telomere length and disease progression.

The study was funded by the US Department of Defense, the National Cancer Institute, Furlotti Family Foundation, Bahna Foundation, DeJoria Foundation, Walton Family Foundation, Resnick Foundation, Greenbaum Foundation, Natwin Foundation, Safeway Foundation, and Prostate Cancer Foundation. Coauthors Jue Lin, Elissa Epel, and Elizabeth H. Blackburn were cofounders of Telome Health, Inc, a diagnostic company that assesses telomere biology. Dr. Rebbeck has disclosed no relevant financial relationships.

Lancet Oncol. Published online September 16, 2013.

    
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