既往有研究發(fā)現(xiàn)維生素D水平對腫瘤發(fā)生發(fā)展有一定的影響，但是并沒有具體的結(jié)論。維生素D水平是否與癌癥患者生存相關(guān)？是否補充維生素D能作為預防腫瘤的手段？近期發(fā)表的兩項研究分別給出了答案。
研究一：癌癥診斷時血液維生素D水平較高與明顯較好的生存期和緩解率相關(guān)
研究人員發(fā)現(xiàn)，癌癥診斷時血液維生素D水平較高與明顯較好的生存期和緩解率相關(guān)。這一結(jié)果來自于一項涉及17,000例以上癌癥患者的綜合薈萃分析。
各個瘤種中25(OH)D水平對生存的影響
研究者們發(fā)現(xiàn)，血液中25-羥基維生素D[25(OH)D]處于較高水平的結(jié)直腸癌和乳腺癌患者的總生存期顯著優(yōu)于那些25(OH)D水平處于較低水平的患者。與最低四分之一的患者相比，25(OH)D最高四分之一中的淋巴瘤患者的總生存期顯著更好。
各個瘤種中25(OH)D水平對生存的影響
血液中維生素D水平較高明顯與結(jié)直腸癌和淋巴瘤患者的癌癥特異性死亡率較低相關(guān)，乳腺癌患者及淋巴瘤患者的無病生存率也有明顯改善。
該研究通訊作者，我國上海生命科學研究院營養(yǎng)科學的王慧教授表示：“這項研究可以被認為是支持血液中25(OH)D水平與癌癥預后存在相關(guān)的最有力的證據(jù)，考慮到維生素D缺乏在世界范圍內(nèi)普遍存在，我們的建議是要確保每個人的這種重要的營養(yǎng)素處于足夠高的水平，也就是說，血液中的25(OH)D水平在75 nmol/L以上。”
在這項薈萃分析中，作者對25項研究，共17,732例癌癥患者進行了研究。來自結(jié)直腸癌，乳腺癌和淋巴瘤的證據(jù)都強烈支持診斷時血液中高水平25(OH)D具有保護作用。研究人員還在肺癌，胃癌，前列腺癌，白血病，黑色素瘤和Merkel細胞癌患者身上觀察到，高水平25(OH)D水平具有保護作用的證據(jù)，證據(jù)雖然有限但很有利。
事實上，當研究人員對40-70nmol/L與<19nmol/L的25(OH)D進行比較后，他們發(fā)現(xiàn)，所有癌癥患者（這些患者均進行了劑量-反應關(guān)系評估）診斷時血液中維生素D水平每升高10nmol/L，則全因死亡率下降4%。
正如王教授所說，研究人員傾向于認為維生素D是一種癌癥化學性預防藥物。“很多實驗室研究表明，維生素D可能通過作用于腫瘤細胞和調(diào)節(jié)腫瘤微環(huán)境來抑制癌癥的進展，此外，維生素D對骨骼健康和免疫系統(tǒng)的生物學作用可能有助于癌癥患者較容易挺過艱難的治療方案，并有助于減輕不良反應。
研究二：缺乏維生素D與歐裔美國男性和非裔美國男性的侵襲性前列腺癌相關(guān)
發(fā)表在臨床癌癥研究的另一項研究稱，缺乏維生素D與歐裔美國男性和非裔美國男性的侵襲性前列腺癌相關(guān)。這些男性患者因列腺特異抗原（PSA）或直腸指檢（DRE）異常而進行首次活檢。全文下載：Clin Cancer Res.2014 May1；20(9):2289-99
結(jié)果表明，25(OH)D水平<12 ng/mL與兩組男性較高的Gleason分級（≥4+4）和較高的臨床分期（腫瘤分期≥cT2b）呈正相關(guān)，但非裔美國男性更具侵略性前列腺癌和缺乏維生素D之間的相關(guān)性較強。
根據(jù)美國國家綜合癌癥網(wǎng)絡(luò)（NCCN）標準，這項研究還發(fā)現(xiàn)25(OH)D低水平與較高的前列腺癌風險之間存在相關(guān)。
“在我們的研究中，缺乏維生素D似乎是歐裔美國男性和非裔美國男性前列腺癌診斷的預測因子 ”芝加哥西北大學范伯格醫(yī)學院泌尿外科副教授，第一作者Adam B. Murphy博士在在一份聲明中評論說。
Murphy博士補充說：“非裔美國人（更具侵略性前列腺癌和缺乏維生素D）強相關(guān)意味著缺乏維生素D在非裔美國男性前列腺癌發(fā)病中作用較大（與歐裔美國男性相比）。維生素D補充給藥可能是預防前列腺癌發(fā)病率和/或前列腺癌患者腫瘤進展的相關(guān)策略。”
Review: The Impacts of Circulating 25-Hydroxyvitamin D Levels on Cancer Patient Outcomes: A Systematic Review and Meta-Analysis
Context: Circulating levels of 25-hydroxyvitamin D [25(OH)D] may affect the prognosis of cancer patients; however, the epidemiological results are not consistent.
Objective: To perform a meta-analysis of all published studies to assess the associations of circulating 25(OH)D levels measured at or near the time of diagnosis and outcomes for cancer patients.
Data Sources: Searches of the PubMed and MEDLINE databases were performed and updated to December 2013.
Study Selection: Studies reporting an association between circulating 25(OH)D levels at or near the time of diagnosis and outcomes for the patients were included.
Data Extraction: Data extraction was performed independently by two authors, and conflicts were resolved by a third investigator.
Data Synthesis: Included in the meta-analysis were 25 studies with 17 332 cases. Significant associations between circulating 25(OH)D levels at or near the time of diagnosis and the outcomes for cancer patients were found. The pooled hazard ratio for the highest vs the lowest quartile of circulating 25(OH)D levels was 0.55 (95% confidence interval [CI] = 0.33–0.91) for overall survival of colorectal cancer patients, 0.63 (95% CI = 0.51–0.77) for breast cancer patients, and 0.48 (95% CI = 0.36–0.64) for lymphoma patients. Higher 25(OH)D levels were significantly associated with reduced cancer-specific mortality for patients with colorectal cancer (P = .005) and lymphoma (P < .001) and improved disease-free survival for patients with breast cancer (P < .001) or lymphoma (P < .05). A 10-nmol/L increment in circulating 25(OH)D levels conferred a hazard ratio of 0.96 (95% CI = 0.95–0.97) for overall survival of the cancer patients.
Conclusions: The results indicate that cancer patients with higher circulating 25(OH)D levels at or near the time of diagnosis have better outcomes.
Affiliations: Key Laboratory of Food Safety Research (M.L., P.C., J.L., R.C., D.X., H.W.), Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai 200031, China; Key Laboratory of Food Safety Risk Assessment (D.X., H.W.), Ministry of Health, Beijing 100021, China; and School of Life Science and Technology (D.X., H.W.), Shanghai Tech University, Shanghai, 200031, China
Vitamin D Deficiency Predicts Prostate Biopsy Outcomes
Purpose: The association between vitamin D and prostate biopsy outcomes has not been evaluated. We examine serum vitamin D levels with prostate biopsy results in men with an abnormal prostate-specific antigen and/or digital rectal examination.
Experimental Design: Serum 25-hydroxyvitamin D (25-OH D) was obtained from 667 men, ages 40 to 79 years, prospectively enrolled from Chicago urology clinics undergoing first prostate biopsy. Logistic regression was used to evaluate the associations between 25-OH D status and incident prostate cancer, Gleason score, and tumor stage.
Results: Among European American (EA) men, there was an association of 25-OH D <12 ng/mL with higher Gleason score ≥ 4+4 [OR, 3.66; 95% confidence interval (CI), 1.41–9.50; P = 0.008] and tumor stage [stage ≥ cT2b vs. ≤ cT2a, OR, 2.42 (1.14–5.10); P = 0.008]. In African American (AA) men, we find increased odds of prostate cancer diagnosis on biopsy with 25-OH D < 20 ng/mL [OR, 2.43 (1.20–4.94); P = 0.01]. AA men demonstrated an association between 25-OH D < 12 ng/mL and Gleason ≥ 4+4 [OR, 4.89 (1.59–15.07); P = 0.006]. There was an association with tumor stage ≥ cT2b vs. ≤ cT2a [OR, 4.22 (1.52–11.74); P = 0.003].
Conclusions: In AA men, vitamin D deficiency was associated with increased odds of prostate cancer diagnosis on biopsy. In both EA and AA men, severe deficiency was positively associated with higher Gleason grade and tumor stage. Clin Cancer Res; 20(9); 2289–99. ©2014 AACR.
