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

Abstract

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. OBJECTIVETo 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 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. CONCLUSIONS AND RELEVANCEIn 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.

Construction of a Prognostic Model Based on Cuproptosis-Related lncRNA Signatures in Pancreatic Cancer

“…Despite recent advances in surgery, chemotherapy, and targeted therapy, the 5-year survival rate of pancreatic cancer patients is only 9% [1,2]. Approximately 80% of patients are not diagnosed until an advanced stage, which limits treatment options [3]. Terefore, the identifcation of diagnostic and prognostic biomarkers is crucial for patients with pancreatic cancer.…”

Pathogenic genomic alterations in Chinese pancreatic cancer patients and their therapeutical implications

“…PALB2 PGVs were statistically more frequent in Chinese patients than in American patients ( p < 0.01), while ATM PGVs showed the opposite trend (Figure 3D). Interestingly, a recent study also showed that PALB2 PGVs were more prevalent in a Chinese PDAC cohort than in an American PDAC cohort from the Johns Hopkins Hospital (6/1009 [0.6%] vs. 2/854 [0.2%]), although the difference was not statistically significant 11 …”

“…Interestingly, a recent study also showed that PALB2 PGVs were more prevalent in a Chinese PDAC cohort than in an American PDAC cohort from the Johns Hopkins Hospital (6/1009 [0.6%] vs. 2/854 [0.2%]), although the difference was not statistically significant. 11 …”

“…The optimal clinical trial design for precision medicine requires the knowledge of actionable genomic variants in cancer patients of different ethnicities. Historically, genomic alteration data for PDAC were largely from patients of European origin, and there was a paucity of therapeutically relevant genomic variant data for Asian patients 8–11 . To address this issue, we set out to profile pathogenic germline and somatic genomic alterations in a large cohort of Chinese PDAC patients ( n = 499) and drafted a molecular roadmap for the practice of precision medicine in PDAC.…”

The distinct genetic features of pancreatic cancer in Chinese population

“… 1 Large cohort studies like TCGA (The Cancer Genome Atlas) revealed the complex somatic molecular landscape of pancreatic cancer and paved the way for precision medicine. 2 For studies in Chinese population, our previous work 3 summarized the germline mutations in 1009 pancreatic cancer patients and performed comparative analysis with cohorts of other races. We found that pathogenic sequence variations were detected in 6.2% of patients with PDAC.…”