Lancet Oncol ：亨廷顿氏症患者癌症风险较低

近日，瑞典研究人员在《柳叶刀肿瘤学》杂志上发表论文称：亨廷顿氏症或其他疾病被称为多聚谷氨酰胺（polyQ蛋白）疾病的罹患癌症的风险较低，其原因为一种常见的遗传机制。

多聚谷氨酰胺（polyQ蛋白）疾病是一种罕见的神经退化性疾病。

多聚谷氨酰胺（polyQ蛋白）疾病包括脊髓延髓性肌萎缩症（SBMA）、亨廷顿氏病（HD），齿状核红核苍白球丘脑下部核萎缩，以及六种类型的脊髓小脑性共济失调。polyQ蛋白疾病患者中枢神经系统的神经元逐步退化。

所有polyQ蛋白疾病具有含有多聚谷氨酰胺的蛋白质积聚在细胞质和/或细胞核中，与许多基因的活性转录因子相互作用。这种积聚最终导致细胞的机械功能障碍和细胞死亡。

隆德大学Jianguang Ji博士和他在瑞典马尔默斯科讷大学医院的研究团队相信，同样的机制可能降低癌症与polyG疾病的患者疾病的发展。研究人员从1969年1月瑞典癌症登记数据分析至2008年12月。

他们发现了与HD 1510例，其中91例（6％）被诊断出患有癌症， 471例spinobulbar性肌萎缩症患者有34例或7％的患者被诊断出患有癌症，以及3,425例hereditary ataxi中有421或12％的患者被诊断为癌症。

我们的研究结果表明，polyQ蛋白疾病能保护患者免受癌症，未来的研??究应探讨polyQ蛋白疾病的患者在减少患癌症的风险的具体相关生物学机制。（生物谷：Bioon.com）

doi:10.1016/S1470-2045(12)70132-8
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Cancer incidence in patients with polyglutamine diseases: a population-based study in Sweden

Dr Jianguang Ji MD, Prof Kristina Sundquist MD and Prof Jan Sundquist MD

Background

Polyglutamine (polyQ) diseases are characterised by the expansion of CAG triplet repeats in specific genes. The accumulated encoded proteins affect the transcription of numerous transcription factors. We investigated whether polyQ diseases reduce the risk of cancer development.

Methods

Data on patients with the polyQ diseases Huntington's disease (HD), spinobulbar muscular atrophy (SBMA), and hereditary ataxia (HA) in Sweden were linked to the Swedish Cancer Registry. We calculated standardised incidence ratios for cancers at specific sites or of specific types and the risks were compared with those in the general population. We also analysed risks in the unaffected parents of patients.

Findings

In the period January, 1969, to December, 2008, we identified 1510 patients with HD, 471 with SBMA, and 3425 with HA. Cancer was diagnosed in 91 (6·0%) HD patients, 34 (7·2%) SBMA patients, and 421 (12·3%) HA patients. The standardised incidence ratios were 0·47 (95% CI 0·38—0·58), 0·65 (0·45—0·91), and 0·77 (0·70—0·85), respectively. Before diagnosis of polyQ disease, the risk of cancer was even lower. Cancer incidence and risk in the unaffected parents of patients with polyQ diseases were similar to those in the general population.

Interpretation

The consistently decreased incidence of cancer in patients with polyQ diseases suggests that a common mechanism protects against the development of cancer. This feature could be related to the polyQ-tract expansion seen in these diseases. Further studies are warranted to investigate the underlying mechanisms linking cancer and polyQ diseases.

Funding

Swedish Cancer Society, Swedish Council for Working Life and Social Research.