Spatial heterogeneity of KRAS mutations in colorectal cancers: A population-based study in northern France

e15101 Background: Somatic mutations in the KRAS gene are present in about 40% of tumors from colorectal cancer (CRC) patients and are associated with a resistance to anti-EGFR therapies. However, no clinical features have been linked to KRAS mutations in CRC. In this study, we attempted to identify the potential geographical population clusters of KRAS mutations in CRC patients in northern France. Methods: All patients with CRC who were identified to have KRAS mutations performed by pyrosequencing between 2008 and 2014 at the Regional Molecular Biology Platform at Lille University Hospital were included. 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. Then, we made an ecological study. Results: 2,486 patients underwent a KRAS status available. A mutation of KRAS codon 12 or 13 performed by pyrosequencing was found in 1,018 patients (40.9%). We report 5 clusters of over-incidence but only one elongated cluster that was statistically significant ranging from the city of Tourcoing to the city of Marquion (Cluster 1; smoothed proportion of KRAS mutation: 0.4570; RR = 1.29; p = 0.0314). The ecological study 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. There was a greater frequency of KRAS mutations in some areas close to major highways and big cities in northern France. Conclusions: There is a spatial heterogeneity of KRAS codon 12 or 13 mutations in CRC 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.