Background: Between 30 and 50% of colon tumors have mutations in the Kirsten-ras (KRAS) gene, which have a large nutritional attributable risk. Despite its high frequency in colorectal cancer (CRC), data to support specific associations between KRAS mutations in CRC and diet are sparse. Here, we conducted a systematic review to summarize the current epidemiological evidence on the association between various dietary factors and KRAS mutations. Methods: PubMed, Science Direct, and Cochrane databases were searched for relevant studies published until December 31, 2019, using inclusion and exclusion criteria in accordance with PRISMA guidelines. We analyzed the studies to find associations between nutritional factors and CRC tumors with KRAS mutations in humans. Results: We identified 28 relevant studies to include in this systematic review. In-depth analyses showed unclear associations between nutritional factors and KRAS mutations in CRC. Most epidemiological studies in the same nutrient or food often reported conflicting and/or inconclusive findings, whereas for some dietary factors, the results were homogeneous. Conclusions: Further research using a more robust prospective cohort study is needed to lend more credence to the epidemiological associations found between KRAS mutations and dietary factors.

Epidemiologic data support an association between diet and mutations in the Kirsten-ras (KRAS) gene involved in colorectal cancer (CRC) development. This study aimed to explore the associations between fat intake and KRAS mutations in codons 12 and 13 in cases of CRC in the Moroccan population. A multicenter case-series study nested in a large-scale Moroccan CRC case-control study was conducted. Among all CRC cases recruited, 151 specimens were available for the DNA mutation analysis. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (Cis) for KRAS mutation status according to the fat intake variables. A KRAS mutation was detected in the CRC tumor of 34.4% of the patients among whom 65.4% had a single mutation at codon 12 and 34.6% had a single mutation at codon 13. Compared to low levels of consumption, a positive association was observed between high polyunsaturated fatty acids (PUFA) consumption (>16.9 g/day) and prevalence of KRAS mutations (OR = 2.15, 95% CI = 1.01–4.59). No statistically significant associations were observed for total fat, monounsaturated fatty acids, saturated fatty acids and KRAS mutations. The results of this study suggest that PUFA may be relevant in the etiology of CRC, possibly through the generation of G > A transitions at the KRAS oncogene. Further studies are needed to verify and explain this finding.

L'anémie de Fanconi est une maladie récessive associée à une instabilité chromosomique, elle est marquée par une hétérogénéité phénotypique qui inclut une insuffisance médullaire, un syndrome malformatif variable, une prédisposition à développer des leucémies aiguës myéloïdes (LAM) et une hypersensibilité cellulaire aux agents pontant l'ADN. Le diagnostic est basé sur l'augmentation anormale du taux de cassures chromosomiques spontanées mais surtout, et de manière spécifique, sur une augmentation nette de ces cassures chromosomiques en présence d'agents alkylants bifonctionnels, ce qui est le cas pour nos six patients. Le conseil génétique rejoint celui des maladies autosomiques récessives. Nous rapportons nos premières observations au CHU Hassan II Fès, confirmées par la mise en évidence d'une grande instabilité chromosomique après culture sous Mitomycine C en comparaison avec un témoin normal. Le but de cet article est la mise à jour de nos connaissances sur la génétique de l'Anémie de Fanconi et à travers ces six observations nous illustrons le rôle de la cytogénétique dans le diagnostic et le conseil génétique pour une meilleure prise en charge aussi bien des enfants atteints que de leurs familles.

Hearing loss (HL) is a common sensory disorder, with syndromic forms accounting for ~30% of genetic cases. Due to phenotypic and genetic heterogeneity, accurate diagnosis remains challenging. Exome sequencing (ES) offers a powerful tool to uncover the underlying genetic causes. This study aimed to investigate the genetic basis of syndromic hearing loss (SHL) in North African Moroccan patients through ES. Seven individuals with suspected SHL were recruited from Hassan II University Hospital, Fez. After clinical and audiological assessments, ES was performed to identify causal genetic variants. Two of the participating individuals had Usher syndrome, and one each had Cornelia de Lange syndrome, Wolfram syndrome, Jervell and Lange-Nielsen syndrome, CHARGE syndrome, and Waardenburg syndrome. The causes of all these syndromes were determined, with pathogenic variants in MYO7A, USH1G, SMC1A, WFS1, KCNQ1, CHD7, and MITF. Across the combined cohort of reported Moroccan SHL cases, variants in CHD7 and MYO7A were among the most frequently observed, while USH1G and MITF variants were rare. This study enhances the understanding of SHL in North Africa, revealing a high level of locus and allelic heterogeneity. Examining disparate populations yields novel insights into the etiology of SHL, which can subsequently enhance genetic diagnosis and tailored management strategies.