Spatial heterogeneity of KRAS mutations in colorectal cancers in northern France
Received 4 April 2019
Accepted for publication 25 July 2019
Published 13 September 2019 Volume 2019:11 Pages 8337—8344
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Nicola Ludin
Peer reviewer comments 2
Editor who approved publication: Dr Beicheng Sun
Anthony Turpin,1–3 Michael Genin,4 Mohamed Hebbar,1,2 Florent Occelli,5 Caroline Lanier,5 Francis Vasseur,4 Clotilde Descarpentries,6 Diane Pannier,7 Anne Ploquin1
1Medical oncology unit, Hôpital Claude Huriez, F-59000 Lille, France; 2Lille University Medical School, Université Lille Nord de France, Lille, France; 3University Lille, CNRS, Institut Pasteur de Lille, UMR 8161 - Mechanisms of Tumorigenesis and Target Therapies, F-59021 Lille, France; 4EA 2694-Santé Publique: épidémiologie et qualité des soins, University Lille, CHU Lille, 59000 Lille, France; 5EA 4483 - Impact de l’environnement chimique sur la santé humaine, University of Lille, 59000 Lille, France; 6Division of Biochemistry and Molecular Biology, Oncology and Molecular Genetics Laboratory, CHU Lille, Lille, France; 7Department of Medical Oncology, Centre Oscar Lambret, Lille, F-59000, France
Correspondence: Anthony Turpin
Medical Oncology Unit, Hôpital Claude Huriez, Rue Michel Polonovski, Lille Cedex 59037, France
Tel +33 32 044 5461
Fax +33 32 044 4381
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: colorectal cancer, KRAS mutation, spatial scan statistics, carcinogens, highways
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