<p>Spatial heterogeneity of <em>KRAS </em>mutations in colorectal cancers in northern France</p>

Abstract

BackgroundSomatic mutations in the KRAS gene are the most common oncogenic mutations found in human cancers. However, no clinical features have been linked to KRAS mutations in colorectal cancer [CRC].PurposeIn this study, we attempted to identify the potential geographical population clusters of KRAS mutations in CRC patients in northern France.Patients and methodsAll patients with CRC who were identified to have KRAS mutations between 2008 and 2014 at the Regional Molecular Biology Platform at Lille University Hospital were included. 2,486 patients underwent a KRAS status available, with 40.9% of CRC with KRAS mutations in northern France. We retrospectively collected demographic and geographic data from these patients. The proportions of KRAS mutation were smoothed to take into account the variability related to low frequencies and spatial autocorrelation. Geographical clusters were searched using spatial scan statistical models.ResultsA mutation at KRAS codon 12 or 13 was found in 1,018 patients [40.9%]. We report 5 clusters of over-incidence but only one elongated cluster that was statistically significant [Cluster 1; proportion of KRAS mutation among CRC: 0.4570; RR=1.29; P=0.0314]. We made an ecological study which did not highlight a significant association between KRAS mutations and the distance to the Closest Waste Incineration Plant, and between KRAS mutations and The French Ecological Deprivation Index but few socio-economic and environmental data were available.ConclusionThere was a spatial heterogeneity and a greater frequency of KRAS mutations in some areas close to major highways and big cities in northern France. These data demand deeper epidemiological investigations to identify environmental factors such as air pollution as key factors in the occurrence of KRAS mutations.

High Probability of Lynch Syndrome among colorectal cancer patients in Indonesia is associated with higher occurrence of KRAS and PIK3CA mutations

“…The frequency of KRAS mutations (exon 2 and exon 3) in our cohort reached 61.88%. This was much higher than what was reported in the Asia-Pacific (37-52%) and Western populations (32-49%) [25][26][27][28][29][30][31][32][33][34][35][36][37][38]. Nevertheless, our data is in line with a previous study in Indonesia, showing that KRAS mutation was found in 71.8% of serrated adenocarcinoma (SA), which is intriguingly higher than the generally reported incidence of 40% [39][40][41].…”

Microsatellite Instability and KRAS Mutation in Stage IV Colorectal Cancer: Prevalence, Geographic Discrepancies, and Outcomes From the National Cancer Database

“…25,26 Still, to date, there are only sparse data on geographic variability of CRC mutations. Turpin et al 27 evaluated patients with CRC from northern France and showed spatial heterogeneity that might correlate with environmental factors, such as proximity to major highways and large cities. The association of KRAS mutation with African American race, female sex, and West South Central US state residence further raises the question of whether the geographic differences of KRAS status are affected by racial distribution differences.…”