scholarly journals Dietary Fat Intake and KRAS Mutations in Colorectal Cancer in a Moroccan Population

Nutrients ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 318
Author(s):  
Achraf El Asri ◽  
Karim Ouldim ◽  
Laila Bouguenouch ◽  
Mohammed Sekal ◽  
Fatima Zahra Moufid ◽  
...  

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.

2019 ◽  
Vol 65 (5) ◽  
pp. 701-707
Author(s):  
Vitaliy Shubin ◽  
Yuriy Shelygin ◽  
Sergey Achkasov ◽  
Yevgeniy Rybakov ◽  
Aleksey Ponomarenko ◽  
...  

To determine mutations in the plasma KRAS gene in patients with colorectal cancer was the aim of this study. The material was obtained from 44 patients with colorectal cancer of different stages (T1-4N0-2bM0-1c). Plasma for the presence of KRAS gene mutation in circulating tumor DNA was investigated using digital droplet polymerase chain reaction (PCR). KRAS mutations in circulating tumor DNA isolated from 1 ml of plasma were detected in 13 (30%) patients with cancer of different stages. Of these, with stage II, there were 3 patients, with III - 5 and with IV - 5. Patients who did not have mutations in 1 ml of plasma were analyzed for mutations of KRAS in circulating tumor DNA isolated from 3 ml of plasma. Five more patients with KRAS mutations were found with II and III stages. The highest concentrations of circulating tumor DNA with KRAS mutation were found in patients with stage IV. The increase in plasma volume to 3 ml did not lead to the identification of mutations in I stage. This study showed that digital droplet PCR allows identification of circulating tumor DNA with the KRAS mutations in patients with stage II-IV of colon cancer. The results can be used to determine the degree of aggressiveness of the tumor at different stages of the disease, but not the 1st, and it is recommended to use a plasma volume of at least 3 ml.


2001 ◽  
Vol 85 (3) ◽  
pp. 333-341 ◽  
Author(s):  
Gösta Samuelson ◽  
Lars-Erik Bratteby ◽  
Rawya Mohsen ◽  
Bengt Vessby

The objective of the present study was to describe the intake of dietary fatty acids among healthy 15-year-old boys and girls and to relate the intake of specific fatty acids and the fatty acid composition of the serum cholesterol esters to serum lipid, apolipoprotein (Apo) and insulin concentrations respectively. Fifty-two girls and forty-two boys were randomly selected from the official population register. Unexpectedly, significant inverse associations were found between the dietary content of saturated fatty acids with a chain length of four to fifteen C atoms, mainly derived from milk fat, as well as the corresponding fatty acids in the serum cholesterol esters, on the one hand and the serum concentrations of cholesterol and ApoB on the other. The estimated dietary intake of 4:0–10:0, 12:0 and 14:0 respectively, were all significantly inversely related to the serum cholesterol (r-0.32,r-0.31,r-0.30, all P<0.05) and ApoB (r-0.42,r-0.42, andr-0.40, all P<0.05) concentrations in girls and 12:0 to the ApoB concentration (r-0.55, P<0.01) in boys. The proportions of 12:0 and 15:0 in the serum cholesterol esters were negatively correlated with the serum cholesterol concentrations in both girls (r-0.34,r-0.32, P<0.05) and boys (r-0.53, P<0.01;r-0.32, P<0.05) and with the ApoB concentrations among boys (r-0.61, P<0.01;r-0.43, P<0.05). It is conceivable that milk fat contains or is associated with some component in the diet, or some other characteristics of the food intake, which counterbalances the expected positive relationships between saturated fat intake and lipid levels.


Author(s):  
Renato Morato ZANATTO ◽  
Gianni SANTOS ◽  
Júnea Caris OLIVEIRA ◽  
Eduardo Marcucci PRACUCHO ◽  
Adauto José Ferreira NUNES ◽  
...  

ABSTRACT Background: KRAS mutations are important events in colorectal carcinogenesis, as well as negative predictors of response to EGFR inhibitors treatment. Aim: To investigate the association of clinical-pathological features with KRAS mutations in colorectal cancer patients treated. Methods: Data from 69 patients with colorectal cancer either metastatic at diagnosis or later, were retrospectively analyzed. The direct sequencing and pyrosequencing techniques were related to KRAS exon 2. The mutation diagnosis and its type were determined. Results: KRAS mutation was identified in 43.4% of patients. The most common was c.35G>T (p.G12V), c.35G>A (p.G12D) and c.38G>A (p.G13D). No correlation was found between KRAS mutation and age (p=0.646) or gender (p=0.815). However, mutated group had higher CEA levels at admission (p=0.048) and codon 13 mutation was associated with involvement of more than one metastatic site in disease progression (p=0.029). Although there was no association between primary tumor site and mutation diagnosis (p=0.568), primary colon was associated with worse overall survival (p=0.009). Conclusion: The KRAS mutation was identified in almost half of patients. Mutated KRAS group had higher levels of CEA at admission and the mutation at codon 13 was associated with involvement of more than one metastatic site in the course of the disease. Colon disease was associated with the worst overall survival.


Nutrients ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1493 ◽  
Author(s):  
Alicia Julibert ◽  
Maria Bibiloni ◽  
Cristina Bouzas ◽  
Miguel Martínez-González ◽  
Jordi Salas-Salvadó ◽  
...  

Background: The effect of dietary fat intake on the metabolic syndrome (MetS) and in turn on cardiovascular disease (CVD) remains unclear in individuals at high CVD risk. Objective: To assess the association between fat intake and MetS components in an adult Mediterranean population at high CVD risk. Design: Baseline assessment of nutritional adequacy in participants (n = 6560, men and women, 55–75 years old, with overweight/obesity and MetS) in the PREvención con DIeta MEDiterránea (PREDIMED)-Plus randomized trial. Methods: Assessment of fat intake (total fat, monounsatured fatty acids: MUFA, polyunsaturated fatty acids: PUFA, saturated fatty acids: SFA, trans-fatty acids: trans-FA, linoleic acid, α-linolenic acid, and ω-3 FA) using a validated food frequency questionnaire, and diet quality using 17-item Mediterranean dietary questionnaire and fat quality index (FQI). Results: Participants in the highest quintile of total dietary fat intake showed lower intake of energy, carbohydrates, protein and fiber, but higher intake of PUFA, MUFA, SFA, TFA, LA, ALA and ω-3 FA. Differences in MetS components were found according to fat intake. Odds (5th vs. 1st quintile): hyperglycemia: 1.3–1.6 times higher for total fat, MUFA, SFA and ω-3 FA intake; low high-density lipoprotein cholesterol (HDL-c): 1.2 higher for LA; hypertriglyceridemia: 0.7 lower for SFA and ω-3 FA intake. Conclusions: Dietary fats played different role on MetS components of high CVD risk patients. Dietary fat intake was associated with higher risk of hyperglycemia.


2007 ◽  
Vol 35 (4) ◽  
pp. 450-457 ◽  
Author(s):  
K Kimura ◽  
T Nagasaka ◽  
N Hoshizima ◽  
H Sasamoto ◽  
K Notohara ◽  
...  

Codon 12 and 13 mutations in 170 colorectal cancer (CRC) and 66 gastric cancer (GC) specimens were analysed by an ‘enriched’ polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) method. All identified mutations were verified by direct sequencing of the second PCR products. Among the 170 CRC specimens, mutations were identified in 47 (28%) and 13 (7.6%) cases in codons 12 and 13, respectively. In the 66 GC specimens examined, however, mutations in codons 12 and 13 were only detected in two (3.0%) and one (1.5%) cases, respectively. Mutations in both codon 12 and 13 were found in 3/170 (1.8%) CRCs and 1/66 (1.5%) GCs. Duplicate mutations were never identified in the same allele, which was confirmed by direct sequencing of the second amplified products. The majority of colorectal and gastric cancer cells with KRAS mutations are homogeneous because they have the same KRAS mutation. A few colorectal or gastric cancers, however, showed heterogeneity, as verified by the fact that single mutations were identified in the same allele.


2002 ◽  
Vol 87 (6) ◽  
pp. 595-604 ◽  
Author(s):  
Ute Alexy ◽  
Wolfgang Sichert-Hellert ◽  
Mathilde Kersting

The DONALD study (Dortmund Nutritional and Anthropometric Longitudinally Designed study) gives the opportunity to evaluate long-term food and nutrient intake data on the basis of 3 d weighed dietary records of infants, children and adolescents since 1985. In this paper, we examine changes in energy and macronutrient intakes (protein, fat, saturated, mono- and polyunsaturated fatty acids, carbohydrates and added sugars) of 795 2–18-year-old subjects between 1985 and 2000 (4483 records). No significant changes in intakes of energy and of protein, polyunsaturated fatty acids and added sugars (as % energy intake, E %) were found. Fat intake decreased significantly in all age groups (between -0·20 and -0·26 E %/year), as well as intake of saturated fatty acids (between -0·11 and -0·14 E %/year) and monounsaturated fatty acids (between -0·07 and -0·014 E %/year). This decline was compensated for by a significant increase in carbohydrate intake (between +0·18 and +0·27 E %/year). The changes in macronutrient intake were mainly due to a decreased consumption of fats–oils (between -0·29 and -1·26 g/year) and meat–fish–eggs (between -0·21 and -2·92 g/year), whereas consumption of bread–cereals (between +0·12 and +2·42 g/year) and potatoes–pasta–rice (between +0·15 and +2·26 g/year) increased slightly. However, since recommended fat intake and fatty acid composition was not reached at the end of the study period by far, further efforts will be necessary to improve macronutrient composition and to stabilize favourable dietary habits.


2003 ◽  
Vol 2003 ◽  
pp. 214-214 ◽  
Author(s):  
A.M. Salter

In 1991 it was recommended that total fat intake in the UK should be reduced to a population average of less that 33% of total daily energy intake and that saturated fatty acids should contribute no more than 10% of total energy (Department of Health, 1991). A further recommendation was that the intake of trans fatty acids should not exceed 2% of total energy. These recommendations were made primarily on the basis of the influence of fatty acids on plasma cholesterol and thereby on the development of cardiovascular disease. While associations of fat intake with other chronic diseases such as cancer, obesity and diabetes have also been suggested, it was felt that there was insufficient evidence to make specific recommendations on the basis of such claims. A reduction in saturated fat intake has remained a central target of public health nutrition within the United Kingdom ever since. Despite concerted efforts, particularly throughout the 1990s., to achieve these targets little progress has been made. In 2000, total fat intake remained at 38% and saturated fatty acid intake at 15% (DEFRA, 2001).


2009 ◽  
Vol 124 (3) ◽  
pp. 678-686 ◽  
Author(s):  
Lesley M. Butler ◽  
Renwei Wang ◽  
Woon-Puay Koh ◽  
Mariana C. Stern ◽  
Jian-Min Yuan ◽  
...  

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3522-3522
Author(s):  
Vlad Calin Popovici ◽  
Eva Budinska ◽  
Arnaud Roth ◽  
Fred Bosman ◽  
Sabine Tejpar ◽  
...  

3522 Background: The BRAF and KRAS mutations have been proposed as prognostic markers in colorectal cancer (CRC). Of them, only the BRAF V600E mutation has been validated as prognostic for overall survival and survival after relapse, while the value of KRAS mutation is still unclear. Methods: In a cohort of 1423 stage II-III patients from the PETACC-3 clinical trial, the prognostic value of the BRAF and KRAS mutations was retrospectively assessed in all possible stratifications defined by the 5 factors (T and N stage, tumor site and grade, and microsatellite instability status), by log rank test for overall survival (OS), relapse-free survival (RFS), and survival after relapse (SAR). The presence of interactions was tested by Wald test. The significance level was set to 0.01 for Bonferroni-adjusted p-values (P*), and a second level for a trend towards statistical significance was set at 0.05 for unadjusted p-values (P). Results: BRAF mutation was a marker of poor OS only in microsatellite stable (MSS) and left-sided tumors, with no prognostic value in microsatellite instable (MSI-H) or right-sided tumors. In MSS/left-sided tumors, BRAF mutation represents a marker of higher risk than previously reported: OS HR=6.4 [95% CI: 3.6-11.5], P* < 0.0001. For SAR, BRAF was prognostic in more stratifications, with higher risk in MSS/left-sided tumors (HR=3.9 [95% CI: 2.1-7.2], P* = 0.0002) than in MSS/right-sided (HR=2.3 [95% CI: 1.2-4.4], P=0.01). A novel observation was that BRAF mutation was prognostic also for RFS, but only in MSS/left-sided tumors (HR=3.6 [95% CI:2-6.3], P*=0.0005]). Additionally, heterogeneity in OS and RFS among BRAF mutants was observed. In general, KRAS mutation did not reach the significance level required, but showed a trend to become a prognostic marker for RFS in MSS tumors with early lymph node involvement (N1) (HR=1.6 [95% CI:1.1-2.2], P=0.01). Conclusions: The prognostic utility of the BRAF and KRAS mutations has to be interpreted in the context of other factors. For the BRAF mutation, a clear interaction with MSI status and tumor site was observed, with BRAF mutation indicating a much higher risk in MSS/left-sided tumors than previously considered.


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