近日，发表在PNAS杂志的一篇研究论文"Cancer Risk Among Patients With Myotonic Muscular Dystrophy"指出，成人肌肉萎缩症患者的癌症风险比普通人要高。
研究人员发现，强直性肌营养不良症患者罹患脑癌、卵巢癌、结肠癌、子宫内膜癌这四种癌症的风险要高于普通人。另外，诸如眼部癌肿、甲状腺癌、胰腺癌、以及好发于女性生殖器部位的癌症发病率在肌肉萎缩症患者人群也有上升。
据医学界人士估计，全美大约有40000人患有强直性肌营养不良，该病是一种以进行性肌肉无力为临床表现的遗传病。根据病人的病程不同，此病有不同的临床表现，主要的临床症状为肌肉僵硬、言语和吞咽困难、行走障碍，部分患者也可有听力障碍和白内障。
罗彻斯特大学医学中心神经病学的Richard T. Moxley医学博士，很早就已知晓肌肉萎缩症患者皮肤生长异常的可能性更大，同时肌肉萎缩症患者所在的家族人员罹患皮肤癌几率也要高于普通人。Moxley与美国国家肿瘤研究院专家以及来自瑞典和丹麦的科学家组成了研究团队对肌肉萎缩症和癌症间的关系进行进一步的研究。
该团队调查了1658例肌肉萎缩症患者的病例记录以详细了解他们的健康状况。在调查的这1658例患者中，有104人患癌，该人群的癌症发病率是全体人群癌症发病率的两倍。
“我们的这些发现提示肌肉萎缩症患者更应重视癌症检查，尤其是结肠癌的检查” Moxley说。Moxley是罗彻斯特大学神经肌肉疾病研究中心主任、神经病学教授。同时他还是罗彻斯特大学Paul D. Wellstone肌肉萎缩症合作研究中心成员，Paul D. Wellstone肌肉萎缩症合作研究中心是美国国家卫生研究院资助的六家研究中心之一。
在过去的15年间，Moxley的同事Charles Thornton医学博士已经发现基因缺陷是强直性肌营养不良症发生的确切病因，所谓的基因缺陷就是基因复制过程中产物分子的片断化(此句不太准确有待斟酌)。该基因缺陷可导致过多的信使RNA在细胞核中积聚，这些冗余的信使RNA可使与肌肉正常生长有关的关键蛋白难以发挥功能。
Moxley认为导致肌肉萎缩症发生的基因缺陷也有可能引起癌症发生。研究人员指出，细胞核内积聚过多的RNA可能会阻碍一些蛋白质参与DNA的修复；而DNA修复机制发生障碍又正是癌症发生的一个原因。另外，他们认为错误基因复制的产物分子与多种癌症的易感基因有密切的联系。
要理清上述病理过程还需要进行更多的相关研究。研究人员计划对Moxley和其同事收集的1600例肌肉萎缩症病例就导致肌肉萎缩症发生的基因缺陷引起癌症发生机制进行更加深入的研究，此研究计划得到了美国国家卫生研究院的资金支持。（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.
