近日,，發(fā)表在PNAS雜志的一篇研究論文"Cancer Risk Among Patients With Myotonic Muscular Dystrophy"指出,，成人肌肉萎縮癥患者的癌癥風(fēng)險(xiǎn)比普通人要高。
研究人員發(fā)現(xiàn),，強(qiáng)直性肌營(yíng)養(yǎng)不良癥患者罹患腦癌,、卵巢癌、結(jié)腸癌,、子宮內(nèi)膜癌這四種癌癥的風(fēng)險(xiǎn)要高于普通人,。另外，諸如眼部癌腫,、甲狀腺癌,、胰腺癌、以及好發(fā)于女性生殖器部位的癌癥發(fā)病率在肌肉萎縮癥患者人群也有上升,。
據(jù)醫(yī)學(xué)界人士估計(jì),，全美大約有40000人患有強(qiáng)直性肌營(yíng)養(yǎng)不良，該病是一種以進(jìn)行性肌肉無力為臨床表現(xiàn)的遺傳病,。根據(jù)病人的病程不同,，此病有不同的臨床表現(xiàn)，主要的臨床癥狀為肌肉僵硬,、言語(yǔ)和吞咽困難,、行走障礙，部分患者也可有聽力障礙和白內(nèi)障,。
羅徹斯特大學(xué)醫(yī)學(xué)中心神經(jīng)病學(xué)的Richard T. Moxley醫(yī)學(xué)博士,，很早就已知曉肌肉萎縮癥患者皮膚生長(zhǎng)異常的可能性更大，同時(shí)肌肉萎縮癥患者所在的家族人員罹患皮膚癌幾率也要高于普通人,。Moxley與美國(guó)國(guó)家腫瘤研究院專家以及來自瑞典和丹麥的科學(xué)家組成了研究團(tuán)隊(duì)對(duì)肌肉萎縮癥和癌癥間的關(guān)系進(jìn)行進(jìn)一步的研究,。
該團(tuán)隊(duì)調(diào)查了1658例肌肉萎縮癥患者的病例記錄以詳細(xì)了解他們的健康狀況。在調(diào)查的這1658例患者中,，有104人患癌,，該人群的癌癥發(fā)病率是全體人群癌癥發(fā)病率的兩倍。
“我們的這些發(fā)現(xiàn)提示肌肉萎縮癥患者更應(yīng)重視癌癥檢查,，尤其是結(jié)腸癌的檢查” Moxley說,。Moxley是羅徹斯特大學(xué)神經(jīng)肌肉疾病研究中心主任、神經(jīng)病學(xué)教授,。同時(shí)他還是羅徹斯特大學(xué)Paul D. Wellstone肌肉萎縮癥合作研究中心成員,，Paul D. Wellstone肌肉萎縮癥合作研究中心是美國(guó)國(guó)家衛(wèi)生研究院資助的六家研究中心之一,。
在過去的15年間,，Moxley的同事Charles Thornton醫(yī)學(xué)博士已經(jīng)發(fā)現(xiàn)基因缺陷是強(qiáng)直性肌營(yíng)養(yǎng)不良癥發(fā)生的確切病因，所謂的基因缺陷就是基因復(fù)制過程中產(chǎn)物分子的片斷化(此句不太準(zhǔn)確有待斟酌),。該基因缺陷可導(dǎo)致過多的信使RNA在細(xì)胞核中積聚,，這些冗余的信使RNA可使與肌肉正常生長(zhǎng)有關(guān)的關(guān)鍵蛋白難以發(fā)揮功能,。
Moxley認(rèn)為導(dǎo)致肌肉萎縮癥發(fā)生的基因缺陷也有可能引起癌癥發(fā)生。研究人員指出,，細(xì)胞核內(nèi)積聚過多的RNA可能會(huì)阻礙一些蛋白質(zhì)參與DNA的修復(fù),；而DNA修復(fù)機(jī)制發(fā)生障礙又正是癌癥發(fā)生的一個(gè)原因。另外,，他們認(rèn)為錯(cuò)誤基因復(fù)制的產(chǎn)物分子與多種癌癥的易感基因有密切的聯(lián)系,。
要理清上述病理過程還需要進(jìn)行更多的相關(guān)研究。研究人員計(jì)劃對(duì)Moxley和其同事收集的1600例肌肉萎縮癥病例就導(dǎo)致肌肉萎縮癥發(fā)生的基因缺陷引起癌癥發(fā)生機(jī)制進(jìn)行更加深入的研究,，此研究計(jì)劃得到了美國(guó)國(guó)家衛(wèi)生研究院的資金支持,。（生物谷Bioon.com）
doi:10.1001/jama.2011.1796
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Cancer Risk Among Patients With Myotonic Muscular Dystrophy
Shahinaz M. Gadalla, MD, PhD;Marie Lund, MD;Ruth M. Pfeiffer, PhD;Sanne Grtz, MSc;Christine M. Mueller, DO;Richard T. Moxley III, MD;Sigurdur Y. Kristinsson, MD, PhD;et al.
Context Myotonic muscular dystrophy (MMD) is an autosomal-dominant multisystem neuromuscular disorder characterized by unstable nucleotide repeat expansions. Case reports have suggested that MMD patients may be at increased risk of malignancy, putative risks that have never been quantified.
Objective To quantitatively evaluate cancer risk in patients with MMD, overall and by sex and age.
Design, Setting, and Participants We identified 1658 patients with an MMD discharge diagnosis in the Swedish Hospital Discharge Register or Danish National Patient Registry between 1977 and 2008. We linked these patients to their corresponding cancer registry. Patients were followed up from date of first MMD-related inpatient or outpatient contact to first cancer diagnosis, death, emigration, or completion of cancer registration.
Main Outcome Measures Risks of all cancers combined and by anatomic site, stratified by sex and age.
Results One hundred four patients with an inpatient or outpatient discharge diagnosis of MMD developed cancer during postdischarge follow-up. This corresponds to an observed cancer rate of 73.4 per 10 000 person-years in MMD vs an expected rate of 36.9 per 10 000 person-years in the general Swedish and Danish populations combined (standardized incidence ratio [SIR], 2.0; 95% CI, 1.6-2.4). Specifically, we observed significant excess risks of cancers of the endometrium (n = 11; observed rate, 16.1/10 000 person-years; SIR, 7.6; 95% CI, 4.0-13.2), brain (n = 7; observed rate, 4.9/10 000 person-years; SIR, 5.3; 95% CI, 2.3-10.4), ovary (n = 7; observed rate, 10.3/10 000 person-years; SIR, 5.2; 95% CI, 2.3-10.2), and colon (n = 10; observed rate, 7.1/10 000 person-years; SIR, 2.9; 95% CI, 1.5-5.1). Cancer risks were similar in women and men after excluding genital organ tumors (SIR, 1.9; 95% CI, 1.4-2.5, vs SIR, 1.8; 95% CI, 1.3-2.5, respectively; P = .81 for heterogeneity; observed rates, 64.5 and 47.7 per 10 000 person-years in women and men, respectively). The same pattern of cancer excess was observed first in the Swedish and then in the Danish cohorts, which were studied sequentially and initially analyzed independently.
Conclusion Patients with MMD identified from the Swedish and Danish patient registries were at increased risk of cancer both overall and for selected anatomic sites.
