Obesity-related genes variability in Czech patients with sporadic colorectal cancer: preliminary results

Vašků, Anna; Vokůrka, J; Bienertová-Vašků, Julie

doi:10.1007/s00384-008-0553-6

Cited by 25 publications

(14 citation statements)

References 24 publications

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“…The association between LEP gene variants and CRC risk has been examined in several epidemiologic studies, and the results were conflicting ( 14 - 18 ). Our results are in line with studies by Slattery et al ( 14 ), Vasku et al ( 15 ), Pechlivanis et al ( 16 ) and by He and Xu ( 18 ), where no association was found between LEP gene rs7799039 variant and CRC risk; nevertheless, Partida-Perez et al ( 17 ) reported a significant association between other variants of this gene and CRC risk. The discrepancy in the reported associations between the LEP gene variants and CRC risk may be due to false positive results, small sample size, statistical methods, genotyped markers, population differences in allele frequencies, or differences in the dietary and lifestyle factors.…”

Section: Discussionsupporting

confidence: 93%

“…In this study, we also analyzed the association between the rs1137101 (Gln223Arg) variant in the exon 6 of LEPR gene and CRC risk. Studies of the effect of LEPR gene variants on CRC risk have also been inconclusive ( 15 , 16 , 19 ). Consistent with our findings, Vasku et al ( 15 ), and Pechlivanis et al ( 16 ) found no association between LEPR gene rs1137101 variant and CRC risk.…”

Section: Discussionmentioning

confidence: 99%

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Genetic Variations in Leptin and Leptin Receptor and Susceptibility to Colorectal Cancer and Obesity

et al. 2016

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BackgroundColorectal cancer (CRC) is the second most commonly diagnosed cancer and the fourth leading cause of cancer-related mortality around the world.ObjectivesWith regard to the role of obesity in colorectal cancer (CRC) and the role of leptin in obesity, we investigated whether leptin (LEP) and leptin receptor (LEPR) gene variants are associated with CRC risk.Patients and MethodsWe evaluated LEP (rs7799039) and LEPR (rs1137101) gene variants by using PCR-RFLP method in 261 cases with CRC and 339 controls.ResultsNo significant difference was found for rs7799039 and rs1137101gene variants between the cases with CRC and controls. However, the LEPR rs1137101 “GG” genotype compared with “AA” genotype and “AA + AG” genotype was associated with increased risks for obesity, and the differences remained significant after adjustment for confounding factors including age, sex, smoking status, and NSAID use (P = 0.015; OR = 2.42, 95%CI = 1.19 - 4.93 and P = 0.016; OR = 2.28, 95%CI = 1.17 - 4.48, respectively). In addition, the LEPR “G” allele compared with the “A” allele was associated with an increased risk for obesity (P = 0.024; OR = 1.44, 95%CI = 1.05 - 1.98).ConclusionsConsistent with most previous studies, our findings found no association between LEP (rs7799039) and LEPR (rs1137101) gene variants and CRC risk. However, the LEPR rs1137101 “GG” genotype compared with the “AA” genotype and “AA+AG” genotype was associated with a 2.42-fold and a 2.28-fold increased risk for obesity, respectively.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Genetic Variations in Leptin and Leptin Receptor and Susceptibility to Colorectal Cancer and Obesity

et al. 2016

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“…Previous reports demonstrated that genetic variation in LEPR affected cancer susceptibility with significantly higher frequency of the LEPR 223Arg allele in patients than in controls [9,11,22,24,33]; however, this association was not be replicated by later studies [14,16,19,23,31,36]. Likewise, previous reports also demonstrated that LEP 2548AA was associated with an increased risk of cancer [12,13,20,21,33,34]; however, replication of this finding by others also failed as well [25,28,31]. …”

Section: Discussionmentioning

confidence: 96%

Association of LEP G2548A and LEPR Q223R Polymorphisms with Cancer Susceptibility: Evidence from a Meta-Analysis

Ruiter

et al. 2013

PLoS ONE

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BackgroundNumerous epidemiological studies have examined associations of genetic variations in LEP (G2548A, -2548 nucleotide upstream of the ATG start site) and LEPR (Q223R, nonsynonymous SNP in exon 6) with cancer susceptibility; however, the findings are inconsistent. Therefore, we performed a meta-analysis to comprehensively evaluate such associations.MethodsWe searched published literature from MEDLINE, EMBASE, Web of Science and CBM for eligible publications. We also assessed genotype-based mRNA expression data from HapMap for rs7799039 (G2548A) and rs1137101 (Q223R) in normal cell lines derived from 270 subjects with different ethnicities.ResultsThe final analysis included 16 published studies of 6569 cases and 8405 controls for the LEP G2548A and 19 studies of 7504 cases and 9581 controls for the LEPR Q223R. Overall, LEP G2548A was statistically significantly associated with an increased risk of overall cancer (AA vs. GG: OR=1.27, 95% CI=1.05-1.54; recessive model: OR=1.19, 95% CI=1.00-1.41). Further stratifications by cancer type showed an increased risk for prostate cancer (recessive model: OR=1.26, 95% CI=1.05-1.51) but not for other cancers. For LEPR Q223R, no statistical evidence for an association with risk of cancer was found for all; however, further stratification by ethnicity showed an increased risk for Africans but not for other ethnicities. No significantly differences in LEP and LEPR mRNA expression were found among genotypes or by ethnicity.ConclusionsDespite some limitations, this meta-analysis found some statistical evidence for an association between the LEP 2548AA genotype and overall risk of cancer, particularly for prostate cancer, but given this variant did not have an effect on mRNA expression, this association warrants additional validation in large and well-designed studies.

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“…RCC risk in relation to genetic variants in AGT has not been previously studied; however, AGT has been linked with other cancers. Specifically, an increased risk of postmenopausal breast cancer was found in a Dutch population among homozygous carriers of the M allele of rs699 (M235T) (26); a significantly higher number of heterozygote carriers of rs5051 (À6G.A) were found among Czech men with colorectal cancer compared with healthy men of similar age (27), and an increased risk of H. pylori-related gastric cancer was observed in a Japanese population among carriers of the C allele of rs5050 (À20A.C) (28). Rs699 is located in exon 2 and encodes a methionine to threonine amino acid change, and rs5051 and rs5050 are both located in the promoter (Figure 1).…”

Section: Gandreotti Et Almentioning

confidence: 99%

Variants in blood pressure genes and the risk of renal cell carcinoma

et al. 2010

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Hypertension is a known risk factor for renal cell carcinoma (RCC), although the underlying biological mechanisms of its action are unknown. To clarify the role of hypertension in RCC, we examined the risk of RCC in relation to 142 single-nucleotide polymorphisms (SNPs) in eight genes having a role in blood pressure control. We analyzed 777 incident and histologically confirmed RCC cases and 1035 controls who completed an in-person interview as part of a multi-center, hospital-based case-control study in Central Europe. Genotyping was conducted with an Illumina GoldenGate Oligo Pool All assay using germ line DNA. Of the eight genes examined, AGT (angiotensinogen) was most strongly associated with RCC (minimum P-value permutation test 5 0.02). Of the 17 AGT tagging SNPs considered, associations were strongest for rs1326889 [odds ratio (OR) 5 1.35, 95% confidence interval (CI) 5 1.15-1.58] and rs2493137 (OR 5 1.31, 95% CI 5 1.12-1.54), which are located in the promoter. Stratified analysis revealed that the effects of the AGT SNPs were statistically significant in participants with hypertension or high body mass index (BMI) ( ‡25 kg/m 2 ), but not in subjects without hypertension and with a normal BMI (<25 kg/m 2 ). Also, haplotypes with riskconferring alleles of markers located in the promoter and intron 1 regions of AGT were significantly associated with RCC compared with the common haplotype in subjects with hypertension or high BMI (global P 5 0.003). Our findings suggest that common genetic variants of AGT, particularly those in the promoter, increase RCC risk among subjects who are hypertensive or overweight.

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Obesity-related genes variability in Czech patients with sporadic colorectal cancer: preliminary results

Cited by 25 publications

References 24 publications

Genetic Variations in Leptin and Leptin Receptor and Susceptibility to Colorectal Cancer and Obesity

Genetic Variations in Leptin and Leptin Receptor and Susceptibility to Colorectal Cancer and Obesity

Association of LEP G2548A and LEPR Q223R Polymorphisms with Cancer Susceptibility: Evidence from a Meta-Analysis

Variants in blood pressure genes and the risk of renal cell carcinoma

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