Type 2 diabetes mellitus, blood cholesterol, triglyceride and colorectal cancer risk in Lynch syndrome

Dashti, S. Ghazaleh; Li, Wing Yan; Buchanan, Daniel D.; Clendenning, Mark; Rosty, Christophe; Winship, Ingrid; Macrae, Finlay; Giles, Graham G.; Hardikar, Sheetal; Hua, Xinwei; Thibodeau, Stephen N.; Figueiredo, Jane C.; Casey, Graham; Haile, Robert W.; Gallinger, Steven; Marchand, Loı̈c Le; Newcomb, Polly A.; Potter, John D.; Lindor, Noralane M.; Hopper, John L.; Jenkins, Mark A.; Win, Aung Ko

doi:10.1038/s41416-019-0580-9

Cited by 12 publications

(9 citation statements)

References 36 publications

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“…Past studies have shown that serum lipids were closely related to cardiovascular diseases 6. In recent years, evidence shows that plasma lipid levels may be closely related to the occurrence and development of cancer7 and thus can be used to evaluate cancer prognosis 8. However, the relationship between lipid profile and CRC has been inconsistent 9 10.…”

Section: Introductionmentioning

confidence: 99%

Relationship between serum lipid level and colorectal cancer: a systemic review and meta-analysis

et al. 2022

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ObjectiveInvestigative studies report contradictory results of the relationship between serum lipid levels and the risk of colorectal cancer (CRC). We conducted a meta-analysis of prospective published studies to clarify the relationship between serum lipid and CRC risk.DesignSystematic review and meta-analysis.Data SourcesPubMed and Embase from inception until December 2020.Eligibility criteriaWe considered prospective cohort and case–control studies that evaluated differences in serum lipid levels with the risk of developing CRC.Data extraction and synthesisTwo independent reviewers screened and included the studies using standardised electronic data extraction forms. The relative risks of the studies were combined with random-effect and fixed-effect models and were analysed for heterogeneity, publication bias and sensitivity.ResultsTwenty-four prospective studies, including 4 224 317 individuals with 29 499 CRC cases, were included in the meta-analysis. The total pooled risk ratio (RR) for high vs low concentrations of triglyceride (TG) concentrations was reported at 1.21 (95% CI 1.09 to 1.34; I2=46.8%), total cholesterol (TC) was at 1.15 (95% CI 1.08 to 1.22; I2=36.8%), high-density lipoprotein cholesterol (HDL-C) was 0.86 (95% CI 0.77 to 0.97; I2=28.8%) and low-density lipoprotein cholesterol (LDL-C) was observed at 1.03 (95% CI 0.75 to 1.41; I2=69.4%).ConclusionsThis meta-analysis shows that high levels of serum TG and TC are positively correlated with the incidence rate of CRC, while high levels of serum HDL-C are negatively correlated with CRC incidence rate. Furthermore, no association was found between LDL-C and the risk of developing CRC. Nevertheless, the heterogeneity brought about by comparative methods, demographic differences and pathological differences between the research subjects limits the effectiveness of the overall pooled results.

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Section: Introductionmentioning

confidence: 99%

Relationship between serum lipid level and colorectal cancer: a systemic review and meta-analysis

et al. 2022

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“…These data suggest that the mismatch repair biological process is somehow related to cholesterol signaling. Patients affect by Lynch syndrome are characterized by mutations in the genes of the mismatch repair GO group ( MLH1 , MSH2 , MSH6 , PMS2 , EPCAM ), determining increased risk of cancer, and this risk is higher in presence of elevated cholesterol levels [ 14 ]. Then, it could be speculated that the increased cancer risk of some patients with Lynch syndrome might be related to the further repression of the mismatch repair related genes by intracellular cholesterol via SRE modulation.…”

Section: Discussionmentioning

confidence: 99%

DeepSRE: Identification of sterol responsive elements and nuclear transcription factors Y proximity in human DNA by Convolutional Neural Network analysis

et al. 2021

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SREBP1 and 2, are cholesterol sensors able to modulate cholesterol-related gene expression responses. SREBPs binding sites are characterized by the presence of multiple target sequences as SRE, NFY and SP1, that can be arranged differently in different genes, so that it is not easy to identify the binding site on the basis of direct DNA sequence analysis. This paper presents a complete workflow based on a one-dimensional Convolutional Neural Network (CNN) model able to detect putative SREBPs binding sites irrespective of target elements arrangements. The strategy is based on the recognition of SRE linked (less than 250 bp) to NFY sequences according to chromosomal localization derived from TF Immunoprecipitation (TF ChIP) experiments. The CNN is trained with several 100 bp sequences containing both SRE and NF-Y. Once trained, the model is used to predict the presence of SRE-NFY in the first 500 bp of all the known gene promoters. Finally, genes are grouped according to biological process and the processes enriched in genes containing SRE-NFY in their promoters are analyzed in details. This workflow allowed to identify biological processes enriched in SRE containing genes not directly linked to cholesterol metabolism and possible novel DNA patterns able to fill in for missing classical SRE sequences.

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“…Compared with traditional diagnostic techniques, such as MRI and CT, which are time-consuming, expensive, and limited in sensitivity, detecting serum tumor markers has a great advantage. Previous studies on serum lipids as risk factors for different cancers are shown in Table 5 [16,[32][33][34][35][36][37].…”

Section: Discussionmentioning

confidence: 99%

The predictive value of serum lipids for eye metastases in male nasopharyngeal carcinoma patients

Xie

Shao

2020

Bioscience Reports

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Background: Nasopharyngeal carcinoma (NPC) is a tumor that is commonly found in southern China. NPC has several risk factors, such as infection with the Epstein–Barr virus. However, we know little about the risk factors for eye metastasis (EM) in male patients with NPC. Serum lipids are well recognized as risk factors for cardiovascular disease, and recent studies show that they also have a relationship with the development of NPC. Purpose: We designed the present study to determine whether they were relevant with the development of EM in male NPC patients by detecting the levels of several serum lipids. Methods: A total of 1140 male patients with NPC were enrolled in this retrospective study and we divided them into two groups: the metastasis (EM) group and non-eye metastasis (NEM) group. A variety of serum lipids between the two groups were tested and compared. Results: There were statistical differences in the levels of serum TG and TC between these two groups. Binary logistic regression showed that TG and TC were independent risk factors for EM in male NPC patients with P=0.004 and P<0.001, respectively. The area under the curve of TG and TC were 0.764 and 0.681, respectively, using cutoff values of 0.975 and 3.425 mmol/l, respectively. We found that TG had higher sensitivity and specificity values with 87.5% and 62.7%, respectively, than TC which were 50.0% and 87.2%. Conclusion: TG and TC are potential risk factors for eye metastases in male NPC patients.

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Type 2 diabetes mellitus, blood cholesterol, triglyceride and colorectal cancer risk in Lynch syndrome

Cited by 12 publications

References 36 publications

Relationship between serum lipid level and colorectal cancer: a systemic review and meta-analysis

Relationship between serum lipid level and colorectal cancer: a systemic review and meta-analysis

DeepSRE: Identification of sterol responsive elements and nuclear transcription factors Y proximity in human DNA by Convolutional Neural Network analysis

The predictive value of serum lipids for eye metastases in male nasopharyngeal carcinoma patients

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