Associations between nutritional factors and KRAS mutations in colorectal cancer: a systematic review

Asri, Achraf El; Zarrouq, B.; Kinany, Khaoula El; Bouguenouch, Laila; Ouldim, Karim; Rhazi, K. El

doi:10.1186/s12885-020-07189-2

Cited by 10 publications

(5 citation statements)

References 93 publications

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“…This is in line with previously reported data in mCRC patients with median levels ranging from 10 to 18 ng/mL [ 15 , 29 ]. Tumor intrinsic features, such as KRAS, NRAS and BRAF mutational status, did not interact with the survival effect of 25(OH)D levels ( p = 0.773) and this was in line with a recently published review [ 30 ]. A further analysis with a larger sample size taking into account the distinct subtypes of KRAS mutations would be of interest given a possible interaction with specific KRAS variants [ 31 ].…”

Section: Discussionsupporting

confidence: 89%

Immune Response in Vitamin D Deficient Metastatic Colorectal Cancer Patients: A Player That Should Be Considered for Targeted Vitamin D Supplementation

Morelli

Rofei

Riondino

et al. 2022

Cancers

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Background: Vitamin D deficiency is a poor prognostic factor in metastatic colorectal cancer (mCRC); however, targeted supplementation trials have so far yielded limited results. We investigated clinical-laboratory parameters influencing vitamin D deficiency, with a particular focus on immune response, and the effect on survival. These parameters could help optimize targeted supplementation therapy. Methods: Association of plasma 25-hydroxyvitamin D (25(OH])D) with overall survival (OS) was assessed with the Hazard Ratio Smoothed Curve with Restricted Cubic Splines (HRSC-RCS) and maximally selected rank statistics (MSRS) in mCRC patients who underwent first-line chemotherapy. Several hematobiochemical variables were evaluated as predictors of vitamin D deficiency by means of Least Absolute Shrinkage and Selection Operator (LASSO) analysis. In a patient subset, peripheral lymphocyte subpopulations were also analyzed. Results: One hundred thirty-three mCRC patients were included. The median(m) baseline 25(OH)D was 10.8 ng/mL (range 3–53.4). HRSC-RCS revealed a linear association between 25(OH)D and OS. MSRS found 10 ng/mL as the optimal 25(OH)D cut-off. The median OS for 25(OH)D < 10 (n = 60) vs. > 10 ng/mL (n = 73) was 12.3 and 24.5 months, respectively (p = 0.002). The LASSO analysis identified high neutrophil-to-lymphocyte ratio (NLR > 3.5) as the strongest predictor of vitamin D deficiency (Odds Ratio 3.35, p 0.0009). Moreover, patients with low 25(OH)D levels (< 10 ng/mL) and high NLR (>3.5) had the shortest survival and patients with 25(OH)D >10 ng/mL and NLR <3.5 had the longest: mOS 8.1 and 28.1 months, respectively, HR 3.40 (1.76–6.59), p 0.0004. Besides the significant difference in NLR between 25(OH)D < and > 10 ng/mL patients (mNLR 3.6 vs. 2.9, p 0.03), the lymphocyte subpopulation analysis revealed that vitamin D deficiency was associated with high T- CD4+ (p = 0.04) and low B (p = 0.03) lymphocyte frequency. Conclusions: NLR is a powerful predictor of Vitamin D deficiency and can further help in stratifying prognosis. Vitamin D deficiency was associated with significant variations in peripheral immune cells. We hypothesize that integrated targeted interventions to both vitamin D and immune system would improve the prognosis of mCRC patients.

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Section: Discussionsupporting

confidence: 89%

Immune Response in Vitamin D Deficient Metastatic Colorectal Cancer Patients: A Player That Should Be Considered for Targeted Vitamin D Supplementation

Morelli

Rofei

Riondino

et al. 2022

Cancers

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“…Significant associations were found between the highest intakes of red meats, cold meats, sausages and the risk of CRC in a case–control study on dietary risk factors for CRC in Morocco [ 63 ]. High levels of animal protein, acrylamide foods, and low levels of vitamin A consumption have been shown to be associated with increased risk of CRC tumors with KRAS mutations [ 64 ]. Polyunsaturated fatty acids (PUFA) may be positively associated with CRC risk by potentially generating G > A transitions in the KRAS oncogene in Moroccan population.…”

Section: Discussionmentioning

confidence: 99%

Prevalence and patterns of mutations in RAS/RAF/MEK/ERK/MAPK signaling pathway in colorectal cancer in North Africa

et al. 2022

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Background Our review discuss (i) the findings from analyzed data that have examined KRAS, NRAS and BRAF mutations in patients with colorectal cancer (CRC) in North Africa and to compare its prevalence with that shown in other populations and (ii) the possible role of dietary and lifestyle factors with CRC risk. Methods Using electronic databases, a systematic literature search was performed for the KRAS, NRAS, and BRAF mutations in CRC patients from Morocco, Tunisia, Algeria and Lybia. Results Seventeen studies were identified through electronic searches with six studies conducted in Morocco, eight in Tunisia, two in Algeria, and one in Libya. A total of 1843 CRC patients were included 576 (31.3%) in Morocco, 641 (34.8%) in Tunisia, 592 (32.1%) in Algeria, and 34 (1.8%) in Libya. Overall, the average age of patients was 52.7 years old. Patients were predominantly male (56.6%). The mutation rates of KRAS, NRAS and BRAF were 46.4%, 3.2% and 3.5% of all patients, respectively. A broad range of reported KRAS mutation frequencies have been reported in North Africa countries. The KRAS mutation frequency was 23.9% to 51% in Morocco, 23.1% to 68.2% in Tunisia, 31.4% to 50% in Algeria, and 38.2% in Libya. The G12D was the most frequently identified KRAS exon 2 mutations (31.6%), followed by G12V (25.4%), G13D (15.5%), G12C (10.2%), G12A (6.9%), and G12S (6.4%). G12R, G13V, G13C and G13R are less than 5%. There are important differences among North Africa countries. In Morocco and Tunisia, there is a higher prevalence of G12D mutation in KRAS exon 2 (≈50%). The most frequently mutation type in KRAS exon 3 was Q61L (40%). A59T and Q61E mutations were also found. In KRAS exon 4, the most common mutation was A146T (50%), followed by K117N (33.3%), A146P (8.3%) and A146V (8.3%). Conclusion KRAS mutated CRC patients in North Africa have been identified with incidence closer to the European figures. Beside established anti-CRC treatment, better understanding of the causality of CRC can be established by combining epidemiology and genetic/epigenetic on CRC etiology. This approach may be able to significantly reduce the burden of CRC in North Africa.

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“…RAS mutation is the most frequent oncogenic alteration in human cancers, and KRAS is the most frequently mutated followed by NRAS. The emblematic KRAS mutant cancers are pancreatic (90%), 17 , 18 colorectal (42.6%), 19 , 20 lung adenocarcinomas (27%) 21 and urogenital cancers. 22 KRAS mutations in CRCs affect codon 12 (>75%), 13, and 61, and CRCs also have NRAS mutations (<5%) at codon 12, 13, or 61.…”

Section: Discussionmentioning

confidence: 99%

An innovative single‐base extension method for synchronous detection of point mutations and MSI status in colorectal cancer

Lin

et al. 2022

Cancer Medicine

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Background An accurate genotyping analysis is one of the critical prerequisites for patients with colorectal cancer receiving matched therapies. Conventional genotyping analysis is currently used to detect either gene mutations or MSI status, delaying the detection of critical tumor biomarkers and thus the optimal time for treatment. An assay that analyzes both biomarkers in a streamlined process is eagerly needed. Methods We developed an assay combining Multiplex PCR Amplification, Single‐base Extension and capillary electrophoresis (CE) analysis (MASE‐CE) for synchronous detection of KRAS/NRAS/BRAF mutations and MSI status. In a 190 colorectal cancer cohort, we identified seven somatic mutations in KRAS, NRAS and BRAF as well as five MSI loci (D2S123/D5S346/D17S250/BAT‐25/BAT‐26) simultaneously. KRAS/NRAS/BRAF mutations were detected by NGS and MASE‐CE, and MSI status were detected by PCR‐CE and MASE‐CE methods. Results The MASE‐CE method showed high consistency with NGS for mutation detection (Kappa value ≥0.8) and PCR‐CE (Kappa value = 0.79). In addition, the limits of detection (LOD) of MASE‐CE assay for MSI and somatic mutation were 5% and 2%, respectively. Conclusions In somatic mutation detection and MSI detection, the LOD of MASE‐CE assay was superior to that of qPCR and NGS. MASE‐CE assay is a highly sensitive, time‐saving and specimen‐saving method, which can greatly avoid the cumbersome testing process and provide clinical decision for doctors in time.

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Associations between nutritional factors and KRAS mutations in colorectal cancer: a systematic review

Cited by 10 publications

References 93 publications

Immune Response in Vitamin D Deficient Metastatic Colorectal Cancer Patients: A Player That Should Be Considered for Targeted Vitamin D Supplementation

Immune Response in Vitamin D Deficient Metastatic Colorectal Cancer Patients: A Player That Should Be Considered for Targeted Vitamin D Supplementation

Prevalence and patterns of mutations in RAS/RAF/MEK/ERK/MAPK signaling pathway in colorectal cancer in North Africa

An innovative single‐base extension method for synchronous detection of point mutations and MSI status in colorectal cancer

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