基于SEER数据库的胃癌患者第二原发淋巴瘤的发病风险及孟德尔随机化研究OA

Objective To investigate the risk of second primary lymphoma in long-term survivors of gastric cancer using the SEER database and to explore the causal relationship between the two using Mendelian randomization(MR).Methods The standardized incidence ratio of second primary lymphoma in gastric cancer long-term survivors was calculated using SEER*Stat.Multivariable Poisson regression was employed to identify risk factors for second primary lymphoma.A two-sample Mendelian randomization(MR)analysis was performed using the R package"TwoSampleMR"to assess the causal effect of gastric cancer on diffuse large B-cell lymphoma.Results The risk of second primary nodal and extranodal non-Hodgkin lymphoma was significantly increased in gastric cancer patients(SIR=1.27,95％CI:1.08-1.48;SIR=1.57,95％CI:1.28-1.91;P＜0.05),with the highest risk observed within the first year after gastric cancer diagnosis.Multivariable Poisson regression revealed that gastric cancer patients aged 60-69 and ≥70 years had a 0.60-fold(95％CI:0.42-0.88,P=0.007)and 0.47-fold(95％CI:0.34-0.66,P＜0.0001)lower risk of second primary lymphoma compared to those aged＜60 years.Black,Asian,or Pacific Islander gastric cancer patients had a 5.01-fold(95％CI:3.28-7.37,P＜0.001)and 2.71-fold(95％CI:1.88-3.80,P＜0.001)higher risk than White patients.Male GC patients had a 0.62-fold lower risk than females(95％CI:0.48-0.79,P＜0.001).The inverse-variance weighted Mendelian randomization analysis demonstrated that gastric cancer was associated with a decreased risk of diffuse large B-cell lymphoma,with an odds ratio(OR)of 0.76(95％CI:0.61-0.94,P=0.012).Conclusion Long-term gastric cancer survivors exhibit an elevated incidence of second primary non-Hodgkin lymphoma,with age,sex,and race being significant influencing factors.However,at the genetic level,GC may confer a protective effect against the development of second primary diffuse large B cell lymphoma.