多发性硬化症患者的癌症风险：一项为期10年的全国性回顾性队列研究

既往文献在多发性硬化症患者（PwMS）中的癌症风险问题上存在分歧。因此，本研究比较了PwMS与法国普通人群中匹配样本的癌症风险。本项为期10年的全国性回顾性匹配队列研究（2012-2021年）利用法国国家行政医疗数据库（覆盖99%的法国人口）数据，确定首次发生癌症的时间。通过患者的长期疾病（LTD）状态、住院记录及多发性硬化症（MS）特异性药物报销情况识别PwMS。对照组按年龄、性别、居住地、保险方案和入组日期进行4:1匹配。入组时无过去3年癌症病史的参与者被纳入。癌症患者通过LTD状态、住院、化疗、放疗或前列腺癌特异性药物报销识别。采用Fine和Gray模型计算整体及特定癌症部位首次发生癌症的危害比（HR），并报告年龄和性别分层的估计值。比较两组在三大国家癌症筛查项目（乳腺、结直肠及宫颈癌）中的筛查参与情况。140,649名PwMS中癌症发病率为每10万人年799例（n=8,368），而562,596名匹配对照组为736例/10万人年（n=31,796）（女性占70.8%；随访时间：7.6 ± 3.2年）。总体上，PwMS的癌症风险略有增加（HR 1.06，95% CI 1.03-1.08），女性中风险更高（HR 1.08，95% CI 1.05-1.11）。不同癌症类型的风险存在差异：前列腺癌（HR 0.80，95% CI 0.73-0.88）、乳腺癌（HR 0.91，95% CI 0.86-0.95）和结直肠癌（HR 0.90，95% CI 0.84-0.97）风险较低，而膀胱癌（HR 1.71，95% CI 1.54-1.89）、脑癌（HR 1.68，95% CI 1.42-1.98）和宫颈癌（HR 1.24，95% CI 1.12-1.38）风险较高。年龄在55岁以下的PwMS中癌症风险更高（HR 1.20，95% CI 1.15-1.24），而65岁及以上的PwMS风险降低（HR 0.89，95% CI 0.85-0.94），这一趋势在所有癌症部位均有体现。PwMS的筛查率低于对照组（所有项目），尤其是在65岁及以上的群体中差异更为显著。PwMS的癌症风险略有增加，尤其是泌尿生殖系统癌症，可能存在监测偏倚。风险随年龄变化，可能与不同代人群的筛查习惯（如老年PwMS的诊断忽视）及风险因素有关。

Previous literature has been diverging on cancer risk in people with multiple sclerosis (PwMS). Therefore, this study compared the risk of cancer in PwMS and a matched sample from the French general population.This 10-year nationwide retrospective matched cohort study (2012-2021) used data from the national French administrative health care database (99% coverage of the French population) to determine the time to the first incident cancer. PwMS were identified using their long-term disease (LTD) status, hospitalizations, and multiple sclerosis (MS)-specific drug reimbursements. The control population was matched 4:1 on age, sex, residence, insurance scheme, and cohort entry date. Participants were included if they had no history of cancer in the 3 years before inclusion. Patients with cancer were identified through LTD status, hospitalizations, chemotherapy, radiotherapy, or prostate cancer-specific drug reimbursements. Overall and cancer location-specific hazard ratios (HRs) for the first incident cancer were obtained from Fine and Gray models, and age- and sex-stratified estimates were reported. Participation in cancer screening through the 3 national programs (breast, colorectal, and cervical) were compared between groups.Cancer incidence was 799 per 100,000 person-years (PYs) (n = 8,368) among the 140,649 PwMS and 736 per 100,000 PYs (n = 31,796) among the 562,596 matched controls (70.8% of women; follow-up: 7.6 ± 3.2 years). A small overall risk increase was observed for PwMS (HR 1.06, 95% CI 1.03-1.08), mostly in women (HR 1.08, 95% CI 1.05-1.11). Risk varied by cancer types and was lower for prostate (HR 0.80, 95% CI 0.73-0.88), breast (HR 0.91, 95% CI 0.86-0.95), and colorectal (HR 0.90, 95% CI 0.84-0.97) cancer and higher for bladder (HR 1.71, 95% CI 1.54-1.89), brain (HR 1.68, 95% CI 1.42-1.98), and cervical (HR 1.24, 95% CI 1.12-1.38) cancer in PwMS. Cancer risk was higher in PwMS younger than 55 years (HR 1.20, 95% CI 1.15-1.24) but decreased in PwMS aged 65 years and older (HR 0.89, 95% CI 0.85-0.94). This trend was found in all cancer locations. There were fewer PwMS getting screened than controls (all programs), with a particularly pronounced difference among those aged 65 years and older.Cancer risk was slightly increased in PwMS, particularly for urogenital cancers, possibly due to surveillance bias. Risk fluctuated depending on age, perhaps due to varying generational screening practices (i.e., diagnosis neglect in the older PwMS) and risk factors.