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. 2019 Sep 13:11:8337-8344.
doi: 10.2147/CMAR.S211119. eCollection 2019.

Spatial heterogeneity of KRAS mutations in colorectal cancers in northern France

Anthony Turpin  1   2   3 , Michael Genin  4 , Mohamed Hebbar  1   2 , Florent Occelli  5 , Caroline Lanier  5 , Francis Vasseur  4 , Clotilde Descarpentries  6 , Diane Pannier  7 , Anne Ploquin  1
Affiliations

Spatial heterogeneity of KRAS mutations in colorectal cancers in northern France

Anthony Turpin et al. Cancer Manag Res. .

Abstract

Background: Somatic 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].

Purpose: In this study, we attempted to identify the potential geographical population clusters of KRAS mutations in CRC patients in northern France.

Patients and methods: All 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.

Results: A 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.

Conclusion: There 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.

Keywords: KRAS mutation; carcinogens; colorectal cancer; highways; spatial scan statistics.

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Conflict of interest statement

A travel grant by Sanofi-Genzyme was obtained by Anthony Turpin. Dr Anthony Turpin reports personal fees from Amgen, Merck, Servier, and grants from Astra-Zeneca, Pfizer, outside of the submitted work. Dr Clotilde Descarpentries reports non-financial support from Astra-Zeneca and Roche, outside the submitted work. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Distribution of KRAS mutation types.
Figure 2
Figure 2
Spatial distribution of smoothed proportions of KRAS mutations in northern France, 2008–2014.
Figure 3
Figure 3
Spatial cluster of high proportion of KRAS mutations identified by elliptic spatial scan statistics, northern France, 2008–2014.
Figure 4
Figure 4
RRs (95% BCI) of KRAS mutation by French EDI and distance (in km) to the CWIP quartiles. Abbreviations: BCI, Bayesian credible interval; EDI, Ecological Deprivation Index; CWIP, closest waste incineration plant.
See this image and copyright information in PMC

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