据报道,中国人群胰腺癌的发病率高于白人人群,但遗传差异迄今未知。家族性和散发性胰腺癌的大样本种系检测主要在白人人群中进行。而在中国人群中的类似研究是有限的。
评估中国胰腺疾病患者种系序列变异的患病率。
这项遗传关联研究是一系列病例,包括在南京医科大学第一附属医院就诊的胰腺导管腺癌(PDAC)或非PDAC胰腺疾病患者的遗传数据,中国,2006年1月至2017年12月(南京队列)。对比组数据来自美国约翰霍普金斯医院(JHH)的队列,来自东亚的人口来自ExomeAggregationConsortium(ExAC)数据库,以及中国地图数据库中来自中国的更多人口。数据在2021年7月进行了更新和分析。
使用下一代测序技术来检查从外周血样本中提取DNA的中国患者的59个基因中有害变异的患病率。Fisher精确检验用于评估研究患者与比较组的种系变异频率之间的差异。
共1009例PDAC患者(627例[62.1%]男性;平均[SD]年龄,62.8[10.2]岁)和885例非PDAC疾病(男性477[53.9%];平均[SD]年龄,来自南京队列的52.0[15.9]年)进行了遗传分析;所有人都是汉族个体。在63例PDAC患者中检测到致病变异(6.2%;95%CI,4.7%-7.7%)。BRCA2的变化(赔率比[OR],3.2;95%CI,1.4-7.7;P=.008)和PALB2(OR,在南京队列中,5.2;95%CI,1.6-17.0;P=.007)与胰腺风险显著相关。与同源重组DNA损伤修复相关的基因的致病变异,包括ATM,BRCA1/2,PALB2,BRIP1,FANCA,FANCC,RAD51D,在34例PDAC患者(3.4%)中发现了XRCC2和XRCC2。没有Ashkenazi犹太人特有的BRCA2变异(p。检测到Ser1982fs)。南京队列与ExAC队列相比,PDAC患者SPINK1变异的比值比为3.2(95%CI,1.8-5.7;P<.001)。在南京队列中未检测到胰腺分泌酶基因CPA1和CPB1的变异。
在这项遗传关联研究中,在来自中国的一个队列中,散发性胰腺癌与致病种系变异相关.这些发现为患有PDAC的汉族人群中胰腺癌的遗传背景提供了见解。
A higher incidence of pancreatic cancer has been reported in the Chinese population compared with the White population, but genetic differences are unknown to date. Large-sample germline testing for both familial and sporadic pancreatic cancers has been conducted predominantly in White populations, whereas similar studies in Chinese populations are limited.
To assess the prevalence of germline sequence variations in patients with pancreatic diseases in
China.
This genetic association study was a case series that included genetic data from patients with pancreatic ductal adenocarcinoma (PDAC) or non-PDAC pancreatic diseases seen at The First Affiliated Hospital of Nanjing Medical University in Nanjing,
China, between January 2006 and December 2017 (Nanjing cohort). Comparator group data were obtained for a US cohort from Johns Hopkins Hospital (JHH), a population from East Asia from the Exome Aggregation Consortium (ExAC) database, and the larger population from
China from the ChinaMAP database. Data were updated and analyzed in July 2021.
Next-generation sequencing technology was used to examine the prevalence of deleterious variations in 59 genes of the included Chinese patients with DNA extracted from peripheral blood samples. The Fisher exact test was used to assess differences among the frequencies of germline variations in the study patients vs the comparator groups.
A total of 1009 patients with PDAC (627 [62.1%] male; mean [SD] age, 62.8 [10.2] years) and 885 with non-PDAC diseases (477 [53.9%] male; mean [SD] age, 52.0 [15.9] years) from the Nanjing cohort were included for genetic analysis; all were Han Chinese individuals. Pathogenic variations were detected in 63 patients with PDAC (6.2%; 95% CI, 4.7%-7.7%). Variations in BRCA2 (odds ratio [OR], 3.2; 95% CI, 1.4-7.7; P = .008) and PALB2 (OR, 5.2; 95% CI, 1.6-17.0; P = .007) were significantly associated with pancreatic risk in the Nanjing cohort. Pathogenic variants of genes associated with homologous recombination DNA damage repair, including ATM, BRCA1/2, PALB2, BRIP1, FANCA, FANCC, RAD51D, and XRCC2, were found in 34 patients with PDAC (3.4%). No Ashkenazi Jewish-specific BRCA2 variation (p.Ser1982fs) was detected. The odds ratio of a SPINK1 variation in patients with PDAC was 3.2 (95% CI, 1.8-5.7; P < .001) in the Nanjing cohort compared with the ExAC cohort. Variations in the pancreatic secretory enzyme genes CPA1 and CPB1 were not detected in the Nanjing cohort.
In this genetic association study, sporadic pancreatic cancer was associated with pathogenic germline variations in a cohort from
China. These findings provide insights into the genetic background of pancreatic cancer in the Han Chinese population with PDAC.