Prevalence of Germline Sequence Variations Among Patients With Pancreatic Cancer in China

Importance

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.

Objective

To assess the prevalence of germline sequence variations in patients with pancreatic diseases in China.

Design, Setting, and Participants

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.

Main Outcomes and Measures

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.

Results

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 inBRCA2(odds ratio [OR], 3.2; 95% CI, 1.4-7.7;P = .008) andPALB2(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, includingATM,BRCA1/2,PALB2,BRIP1,FANCA,FANCC,RAD51D, andXRCC2, were found in 34 patients with PDAC (3.4%). No Ashkenazi Jewish–specificBRCA2variation (p.Ser1982fs) was detected. The odds ratio of aSPINK1variation 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 genesCPA1andCPB1were not detected in the Nanjing cohort.

Conclusions and Relevance

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.