BSR2013：风湿性多肌痛可在短期内显著增加癌症风险

日前，一项纳入12,000多人的一级保健匹配队列研究显示，在诊断为风湿性多肌痛(PMR)后的前6个月内，患者癌症风险几乎增加近1倍，危险比(HR)为1.96。英国基尔大学一级保健和健康科学研究所的Sara Muller博士及其同事称，6个月后，癌症风险下降，诊断后6~12个月的危险比为1.03，1~2年后的危险比为1.04，2~5年后的危险比为1.05，5~10年后的危险比为1.1，10年后的危险比为1.00。

Sara Muller

她在英国风湿病学会(BSR)2013年会上补充道，癌症诊断率的下降可能是鉴别诊断问题的反映，即早期癌症症状可能被诊断为PMR。Muller医生建议，诊断后的6个月内应密切监视PMR患者。进一步的研究应着眼于应如何从有限关节症状的PMR患者中鉴定出哪些有实质性的癌变风险。

PMR是一种老年人群中最常见的炎性风湿病。鉴于已发现类风湿性关节炎与淋巴瘤之间存在关联，这一研究旨在阐明PMR与癌症之间是否存在关系。病例报道显示PMR经常被误诊为肾脏、睾丸、胃、或血液学（淋巴瘤）肿瘤。一项瑞典研究(Rheumatology 2010;49:1158-63)的结果显示，诊断为PMR或巨细胞动脉炎的患者癌症风险有轻微增加。以上都是二级护理研究。Muller医生和他的合作者打算从一级护理人群入手进行研究，这一人群中包含了大部分的诊断并治疗的PMR患者。

研究人员在英国综合实践研究数据库(GPRD，现称为临床实践研究数据链)中查找到1987~1999年间被诊断为PMR的2,877例年龄≥50岁的患者。研究者随后将每例PMR患者与5例非PMR对照者(n=9,942)进行匹配，并评估1987~2011年间癌症的发生情况。该研究排除有癌症或血管疾病既往史的患者。受试者中73%为女性，平均年龄为72岁。中位观察时间为7.8年，一些患者的随访时间超过20年。在观察期间，PMR患者中有667人(23.2%)被诊断为癌症，非PMR对照者中有1,938人(19.5%)被诊断为癌症，癌症诊断率分别为27.7/1,000人-年和24.4/1,000人-年。

Muller 医生观察到，PMR患者的泌尿生殖系统癌(主要为前列腺癌)发生率高于非PMR对照者。此外，PMR患者的淋巴系统和造血组织癌及被GPRD编码系统归类为“其他”癌症的发生率也高于非PMR对照者。相反，PMR患者的骨癌、结缔组织癌、皮肤癌和乳腺癌、消化系统癌和腹膜癌、呼吸道癌和胸腔内器官癌的发生率有低于非PMR对照者的趋势，但差异无统计学显著性。研究者表示，虽然所采用的数据库收集了大量的癌症资料，但这方面的病例数量仍不够多，仍然无法获得足够的数据以得出任何正式的统计学分析结论。该研究获英国皇家全科医师协会科学基金会董事会资助。Muller医生声明无任何经济利益冲突。

对于类固醇治疗无效的患者应考虑恶性肿瘤的可能

英国基尔大学全科医生Davenport博士表示，不出意料，该研究结果与其在35年临床实践中观察到的一致。假如癌症发病率在诊断后6个月至1年内增加会使人感到惊讶，因为这可能意味着类固醇治疗对免疫系统有影响。未来需开展进一步研究，探讨是否有某些预测因素能够区分PMR和癌症。如果新诊断PMR的患者在接受类固醇治疗后(通常为1周内)疗效不明显，则强烈建议考虑恶性肿瘤的可能性。有助于明确癌症诊断的检查包括骨髓瘤筛查、胸部X射线和肌酐激酶测定。Davenport博士声明无与该研究相关的经济利益冲突。

与癌症相关的拓展阅读：

• NEJM：癌症特征决定于基因图谱而非发病器官
• Cell：癌症基因组沉思录
• STM：中外学者开发荧光肽技术助力癌症诊断
• Onco & Cancer Res：袁增强等Hippo信号通路和癌症及细胞衰老研究获进展
• EBM：以崭新之生物医学造影技术研究癌症发展模式 更多信息请点击：有关癌症更多资讯

Polymyalgia rheumatica carries postdiagnosis cancer risk
In the first 6 months after the diagnosis of polymyalgia rheumatica, the risk of cancer was almost doubled, with a hazard ratio of 1.96, in a primary care–based matched cohort study of more than 12,000 individuals.
After 6 months, the cancer risk subsided, with a hazard ratio of 1.03 at 6-12 months after diagnosis, 1.04 at 1-2 years, 1.05 at 2-5 years, 1.1 at 5-10 years, and 1.00 after 10 years, reported Sara Muller, Ph.D., of the Research Institute for Primary Care & Health Sciences, Keele University, England.
The drop-off in cancer diagnosis may reflect "a differential diagnosis issue. Maybe there are early cancer symptoms that are being diagnosed as PMR [polymyalgia rheumatica]," she added at the British Society for Rheumatology annual conference.
Monitor PMR patients closely for the first 6 months after diagnosis, Dr. Muller advised. Future research needs to try to tease out how to identify PMR patients who might actually have cancer from those whose condition is limited to joint problems.
PMR is the most common inflammatory rheumatologic condition in older adults. The study was performed to see if there was any link between PMR and cancer, as has been seen for rheumatoid arthritis and lymphoma.
Case reports indicate PMR has been misdiagnosed as renal, testicular, gastric, or hematologic (lymphoma) cancer. The results of a Swedish study (Rheumatology 2010;49:1158-63) suggest that cancer risk is slightly increased in patients diagnosed with PMR or giant cell arteritis. These were all secondary care studies, however, so Dr. Muller and her associates decided to look at a primary care population, where most cases of PMR are diagnosed and treated.
Using the U.K. General Practice Research Database (GPRD), now known as the Clinical Practice Research Datalink, the research team identified 2,877 cases of PMR in individuals aged 50 years or older who were diagnosed between 1987 and 1999. Each case was then matched to five individuals without PMR as controls (n = 9,942). The development of cancer was assessed from 1987 to 2011. Patients with a prior history of cancer or vascular disease were excluded from the study. The cohort was 73% female, and the mean age of the study population was 72 years.
The median observation time was 7.8 years, with some patients followed for more than 20 years. During this time, 667 (23.2%) cases of cancer were diagnosed in patients with PMR and 1,938 (19.5%) in those without, giving respective cancer diagnosis rates of 27.7 and 24.4 per 1,000 person-years. {nextpage}
"In those people with PMR, there were more genitourinary cancers, which were mainly prostate cancers, than in those without PMR," observed Dr. Muller. She added that there were also more cancers affecting the lymphatic system and hematopoietic tissue, and unspecified cancers categorized as "other" by the GPRD coding system.
Conversely, PMR patients were less likely than those without PMR to have cancers of the bone, connective tissue, skin and breast, digestive system and peritoneum, and the respiratory tract and intrathoracic organs.
However, these were only trends and not statistically significant. "We could not really look at the statistical significance of these differences in types of cancer because, despite this being possibly one of the largest datasets where you would find this kind of information, we still didn’t really have enough numbers to make any formal statistical analysis," Dr. Muller said.
The Royal College of General Practitioners Scientific Foundation Board supported the research. Dr. Muller had no conflicts of interest.