Impact of Ethnicity on Somatic Mutation Rates of Pancreatic Adenocarcinoma

Abstract

Background/Aim: Ethnicity has an effect on survival in patients with pancreatic adenocarcinoma (PDAC), which may be reflected in the rate of somatic driver mutations. The Brazilian population represents au extensive interethnic admixture and little is known about the spectrum and rates of somatic driver mutations in Brazilian PDAC cases. Materials and Methods: Direct sequencing of six genes in 23 PDAC cases was performed and the ancestry of patients was determined using a validated panel of ancestry-informative insertion/ deletion DNA polymorphisms. Results: KRAS proto-oncogene (KRAS) was the most commonly mutated gene (60%). A novel putatively pathogenic mutation in phosphatidylinositol-4,5bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) (c.2948T>A; p.M983K) was identified. Mutations in epidermal growth factor receptor (EGFR) (4%), PIK3CA (4%), cyclindependent kinase inhibitor 2A (CDKN2A) (4%) and TP53 (8%) were noted, in rates that are less frequent than those reported for other populations. Mutations of B-Raf proto-oncogene, serine/threonine kinase (BRAF) were not present. All individuals with high African ancestral component (allelic frequency, >0.45) exhibited KRAS mutations. Conclusion: Our results highlight the importance of the effect of ethnicity on somatic mutations in Brazilian patients with PDAC. References 1 Coupland VH, Kocher HM, Berry DP, Allum W, Linklater KM, Konfortion J, Moller H and Davies EA: Incidence and survival for hepatic, pancreatic and biliary cancers in England between

Genetic mapping of pancreatic cancer by targeted next-generation sequencing in a cohort of patients managed with nab-paclitaxel-based chemotherapy or agents targeting the EGFR axis: a retrospective analysis of the Hellenic Cooperative Oncology Group (HeCOG)

“…The observed lower KRAS mutation rates may be due to study sample bias, different genetic or ethnic characteristics or geography-related environmental factors, particularly dietary, according to a Spanish study10 and possibly air-pollution parameters 11. Still, it definitely raises a question regarding the most common pathogenic mutation of pancreatic cancer in Greek or southeast Mediterranean natives, similarly to reports from further geographical areas 12 13…”

Pancreatic cancer: A review of epidemiology, trend, and risk factors

“…Gad et al [ 62 ] found that the incidence of pancreatic cancer among Asian-Americans, especially malignancies of the body and tail of the pancreas, as well as the mortality based on the incidence, was overall on the rise in an epidemiological study, without respect to age, sex, or stage subgroup. Amaral et al [ 63 ] also emphasized the importance of the influence of ethnicity on somatic mutations in Brazilian patients with PDAC. To elucidate the reasons for the racial differences in the incidence of pancreatic cancer may help us improve the understanding and prevention of this disease.…”