Division of Molecular Genetic Epidemiology, German Cancer Research Centre (DKFZ), Heidelberg, Germany.
Ann Oncol. 2014 Feb;25(2):511-8. doi: 10.1093/annonc/mdt544. Epub 2014 Jan 9.
Systemic amyloidoses include immunoglobulin light chain (AL) amyloidosis, serum amyloid (AA)-related amyloidosis and senile systemic amyloidosis (SSA). AL amyloidosis is associated with myeloma, and we showed recently that transthyretin-related hereditary amyloidosis was related to non-Hodgkin lymphoma (NHL). In SSA, amyloids constitute wild-type transthyretin. We wanted to analyze cancer risks in amyloidosis, particularly in SSA.
Nonhereditary amyloidosis patients were identified from the Swedish Hospital Discharge and Outpatients Registers from years 1997 through 2010. Their cancer risk was assessed based on the Swedish Cancer Registry using standardized incidence ratio (SIR) between amyloidosis patients and the remaining population. To gain information about amyloidosis subtypes, we used the Swedish Prescribed Drug Register from years 2005 through 2010 to find out the specific medication prescribed.
Among 1400 identified amyloidosis patients, cancer risk was increased for myeloma, NHL and squamous cell skin cancer. Myeloma and skin cancers were diagnosed 7-8 years earlier than in the population, whereas NHL was diagnosed in elderly patients. The SIR was 204 for myeloma in patients who received AL amyloidosis medication, and it was 17.22 in patients receiving rheumatoid arthritis medication, suggesting AA amyloidosis. In remaining patients, including SSA, NHL risk was 14.78, including lymphoplasmacytic lymphoma and Waldenstrom macroglobulinemia (51.41) and diffuse large B-cell lymphoma (18.69). In these patients, endometrial cancer (7.04) and cancer of unknown primary site (6.56) were also increased.
SSA is likely to be a main cause of NHL in the elderly population. The present findings suggest a novel mechanism for amyloidosis-related cancer, highlighting the role of chronic stimulation by amyloid.
系统性淀粉样变包括免疫球蛋白轻链（AL）淀粉样变性、血清淀粉样蛋白（AA）相关淀粉样变性和老年性系统性淀粉样变性（SSA）。AL 淀粉样变性与骨髓瘤有关，我们最近发现转甲状腺素相关遗传性淀粉样变性与非霍奇金淋巴瘤（NHL）有关。在 SSA 中，淀粉样物质构成野生型转甲状腺素。我们希望分析淀粉样变性的癌症风险，特别是 SSA。
从 1997 年至 2010 年，从瑞典医院出院和门诊登记处确定了非遗传性淀粉样变性患者。根据瑞典癌症登记处，使用标准化发病率比（SIR）评估他们的癌症风险，比较淀粉样变性患者和其余人群。为了获得淀粉样变性亚型的信息，我们使用 2005 年至 2010 年的瑞典处方药物登记处，了解具体的药物处方。
在 1400 名确定的淀粉样变性患者中，癌症风险增加了骨髓瘤、NHL 和鳞状细胞皮肤癌。骨髓瘤和皮肤癌的诊断比人群早 7-8 年，而 NHL 则在老年患者中诊断。接受 AL 淀粉样变性药物治疗的患者中骨髓瘤的 SIR 为 204，接受类风湿关节炎药物治疗的患者为 17.22，提示 AA 淀粉样变性。在其余患者中，包括 SSA，NHL 风险为 14.78，包括淋巴浆细胞淋巴瘤和瓦尔登斯特伦巨球蛋白血症（51.41）和弥漫性大 B 细胞淋巴瘤（18.69）。在这些患者中，子宫内膜癌（7.04）和不明原发部位癌（6.56）也增加。
SSA 可能是老年人群 NHL 的主要原因。本研究结果提示淀粉样变性相关癌症的新机制，强调了淀粉样物质慢性刺激的作用。
