Risk of Lymphoproliferative Malignancy in Relation to Small Intestinal Histopathology Among Patients With Celiac Disease
Risk of Lymphoproliferative Malignancy in Relation to Small Intestinal Histopathology Among Patients With Celiac Disease
复制标题
DOI：
10.1093/jnci/djq564
复制
发表时间：
2011-03-01
影响因子：
10.3
通讯作者：
Ludvigsson, Jonas F.
中科院分区：
文献类型：
--
作者：
Elfstrom, Peter;Granath, Fredrik;Ludvigsson, Jonas F.
背景乳糜泻与恶性淋巴瘤的风险增加有关。没有绒毛萎缩的小肠炎症患者和潜伏性乳糜泻患者发生淋巴增生性恶性肿瘤的风险尚不清楚。方法：我们进行了一项队列研究，使用从瑞典所有28个病理部门收集的十二指肠和空肠活检数据（1969年7月至2008年2月）。我们确定了两个基于人群的队列，包括28989例活检证实的乳糜泻（绒毛萎缩，Marsh期3）和13140例无绒毛萎缩的小肠炎症（Marsh 1 + 2），以及3711例潜伏性乳糜泻（乳糜泻血清学阳性和粘膜正常）的区域队列。癌症数据是通过与国家癌症登记处的联系获得的。我们使用Cox回归来估计三个队列中淋巴增生性恶性肿瘤和任何实体癌的风险比（hr），并与222911名年龄和性别匹配的参考个体进行比较。结果虽然活检证实的乳糜泻和肠道炎症与淋巴细胞增生性恶性肿瘤相关（乳糜泻的HR = 2.82, 95%可信区间[CI] = 2.36 ~ 3.37, n = 193；炎症的HR = 1.81, 95% CI = 1.42 ~ 2.31, n = 89），但潜伏性乳糜泻与淋巴细胞增生性恶性肿瘤无关（HR = 0.97, 95% CI = 0.44 ~ 2.14, n = 7）。在患有乳糜泻、小肠炎症和潜伏性乳糜泻的人群中，淋巴增殖性恶性肿瘤的绝对发病率分别为70.3 / 10万人年、83.4 / 10万人年和28.0 / 10万人年。与患有乳糜泻的个体相比，患有小肠炎症或潜伏性乳糜泻的个体发生淋巴增生性恶性肿瘤的风险在统计学上显著降低。在任何队列中，任何实体癌的风险在随访的第一年之后都没有增加。乳糜泻与霍奇金淋巴瘤以及t细胞和b细胞非霍奇金淋巴瘤相关。结论乳糜泻患者发生淋巴增生性恶性肿瘤的风险与小肠组织病理学有关，潜伏性乳糜泻患者发生淋巴增生性恶性肿瘤的风险不增加。
Background Celiac disease is associated with an increased risk of malignant lymphomas. The risk of lymphoproliferative malignancies in patients with small intestinal inflammation without villous atrophy and in patients with latent celiac disease is unknown.Methods We performed a cohort study using duodenal and jejunal biopsy data that were collected from all 28 Swedish pathology departments (July 1969 to February 2008). We identified two population-based cohorts composed of 28 989 individuals with biopsy-verified celiac disease (villous atrophy, Marsh stage 3) and 13 140 individuals with small intestinal inflammation without villous atrophy (Marsh 1 + 2) and a regional cohort of 3711 individuals with latent celiac disease (positive celiac disease serology and normal mucosa). Cancer data were obtained by linkage to the National Cancer Registry. We used Cox regression to estimate hazard ratios (HRs) for lymphoproliferative malignancy and any solid cancer among the three cohorts compared with a total of 227 911 age-and sex-matched reference individuals.Results Although biopsy-verified celiac disease and intestinal inflammation were associated with lymphoproliferative malignancy (for celiac disease, HR = 2.82; 95% confidence interval [CI] = 2.36 to 3.37, n = 193; for inflammation, HR = 1.81; 95% CI = 1.42 to 2.31, n = 89), latent celiac disease was not associated with lymphoproliferative malignancy (HR = 0.97; 95% CI = 0.44 to 2.14, n = 7). The absolute rates of lymphoproliferative malignancies among persons with celiac disease, small intestinal inflammation, and latent celiac disease were 70.3 per 100 000 person-years, 83.4 per 100 000 person-years, and 28.0 per 100 000 person-years, respectively. Compared with individuals with celiac disease, individuals with small intestinal inflammation or latent celiac disease were at a statistically significantly lower risk of lymphoproliferative malignancy. Risk of any solid cancer was not increased beyond the first year of follow-up in any cohort. Celiac disease was associated with Hodgkin lymphoma and both T-cell and B-cell non-Hodgkin lymphomas.Conclusion The risk of lymphoproliferative malignancy in celiac disease is dependent on small intestinal histopathology, with no increased risk in latent celiac disease.