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險比普通人要高,。
研究人員發(fā)現，強直性肌營養(yǎng)不良癥患者罹患腦癌、卵巢癌,、結腸癌、子宮內膜癌這四種癌癥的風險要高于普通人,。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。
據醫(yī)學界人士估計,，全美大約有40000人患有強直性肌營養(yǎng)不良,，該病是一種以進行性肌肉無力為臨床表現的遺傳病。根據病人的病程不同,，此病有不同的臨床表現,，主要的臨床癥狀為肌肉僵硬,、言語和吞咽困難、行走障礙,，部分患者也可有聽力障礙和白內障,。
羅徹斯特大學醫(yī)學中心神經病學的Richard T. Moxley醫(yī)學博士，很早就已知曉肌肉萎縮癥患者皮膚生長異常的可能性更大,，同時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與美國國家腫瘤研究院專家以及來自瑞典和丹麥的科學家組成了研究團隊對肌肉萎縮癥和癌癥間的關系進行進一步的研究。
該團隊調查了1658例肌肉萎縮癥患者的病例記錄以詳細了解他們的健康狀況,。在調查的這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)現提示肌肉萎縮癥患者更應重視癌癥檢查,，尤其是結腸癌的檢查” Moxley說。Moxley是羅徹斯特大學神經肌肉疾病研究中心主任,、神經病學教授,。同時他還是羅徹斯特大學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國家衛(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)學博士已經發(fā)現基因缺陷是強直性肌營養(yǎng)不良癥發(fā)生的確切病因，所謂的基因缺陷就是基因復制過程中產物分子的片斷化(此句不太準確有待斟酌),。該基因缺陷可導致過多的信使RNA在細胞核中積聚,，這些冗余的信使RNA可使與肌肉正常生長有關的關鍵蛋白難以發(fā)揮功能。
Moxley認為導致肌肉萎縮癥發(fā)生的基因缺陷也有可能引起癌癥發(fā)生,。研究人員指出,，細胞核內積聚過多的RNA可能會阻礙一些蛋白質參與DNA的修復；而DNA修復機制發(fā)生障礙又正是癌癥發(fā)生的一個原因,。另外,，他們認為錯誤基因復制的產物分子與多種癌癥的易感基因有密切的聯系。
要理清上述病理過程還需要進行更多的相關研究,。研究人員計劃對Moxley和其同事收集的1600例肌肉萎縮癥病例就導致肌肉萎縮癥發(fā)生的基因缺陷引起癌癥發(fā)生機制進行更加深入的研究,，此研究計劃得到了美國國家衛(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.
