Allelic imbalance of the TGFβR1 is not a major contributor to the genetic predisposition to colorectal cancer

Abadie, Caroline; Killian, Audrey; Tinat, Julie; Bougeard, Marion; Medhaoui, D; Af, Cailleux; Baert‐Desurmont, Stéphanie; Frébourg, Thierry

doi:10.1038/bjc.2011.124

Cited by 4 publications

(6 citation statements)

References 6 publications

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“…More recently, contrary results were reported, in that the ASE of TGFBR1 was observed as a rare event and no increased susceptibility to CRC could be detected [9]–[14].…”

Section: Introductionmentioning

confidence: 69%

“…Recently, a phenomenon called “allele-specific expression” (ASE) was described; ASE occurs in the germline at the TGFBR1 gene in 10%–20% of CRC patients and generates an increased risk of CRC (odds ratio [OR]: 8.7; 95% confidence interval [CI]: 2.6–29.1), although the underlying genetic cause of this transcriptional variation remains unknown [8] . More recently, contrary results were reported, in that the ASE of TGFBR1 was observed as a rare event and no increased susceptibility to CRC could be detected [9] – [14] .…”

Section: Introductionmentioning

confidence: 69%

“…Moreover, cumulative effects, epistasis, genotype-environment interactions, and pleiotropy may account for the complex genetic architecture underlying these transcriptional variations [22] . Plausible heterogeneity in regulatory factors, differences in selected cohorts of CRC patients, and differences in methodological approaches may be responsible for the apparently incongruent results published for TGFBR1 ASE [8] – [14] .…”

Section: Discussionmentioning

confidence: 99%

“…For these reasons, the use of bulk nontransformed cells or ex vivo cells is recommended for ASE assays [22] . All previously reported TGFBR1 ASE studies used SNPs as genetic markers [8] – [14] . SNaPshot [8] , [9] , [11] and pyrosequencing [10] , [12] – [14] technologies have been used to analyze SNPs, and have generated discrepancies in published TGFBR1 ASE results.…”

Section: Discussionmentioning

confidence: 99%

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TGFBR1 Intralocus Epistatic Interaction as a Risk Factor for Colorectal Cancer

et al. 2012

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In colorectal cancer (CRC), an inherited susceptibility risk affects about 35% of patients, whereas high-penetrance germline mutations account for <6% of cases. A considerable proportion of sporadic tumors could be explained by the coinheritance of multiple low-penetrance variants, some of which are common. We assessed the susceptibility to CRC conferred by genetic variants at the TGFBR1 locus. We analyzed 14 polymorphisms and the allele-specific expression (ASE) of TGFBR1 in 1025 individuals from the Spanish population. A case-control study was undertaken with 504 controls and 521 patients with sporadic CRC. Fourteen polymorphisms located at the TGFBR1 locus were genotyped with the iPLEX Gold (MassARRAY-Sequenom) technology. Descriptive analyses of the polymorphisms and haplotypes and association studies were performed with the SNPator workpackage. No relevant associations were detected between individual polymorphisms or haplotypes and the risk of CRC. The TGFBR1*9A/6A polymorphism was used for the ASE analysis. Heterozygous individuals were analyzed for ASE by fragment analysis using cDNA from normal tissue. The relative level of allelic expression was extrapolated from a standard curve. The cutoff value was calculated with Youden's index. ASE was found in 25.4% of patients and 16.4% of controls. Considering both bimodal and continuous types of distribution, no significant differences between the ASE values of patients and controls were identified. Interestingly, a combined analysis of the polymorphisms and ASE for the association with CRC occurrence revealed that ASE-positive individuals carrying one of the most common haplotypes (H2: 20.7%) showed remarkable susceptibility to CRC (RR: 5.25; 95% CI: 2.547–5.250; p<0.001) with a synergy factor of 3.7. In our study, 54.1% of sporadic CRC cases were attributable to the coinheritance of the H2 haplotype and TGFBR1 ASE. These results support the hypothesis that the allelic architecture of cancer genes, rather than individual polymorphisms, more accurately defines the CRC risk.

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“…More recently, contrary results were reported, in that the ASE of TGFBR1 was observed as a rare event and no increased susceptibility to CRC could be detected [9]–[14].…”

Section: Introductionmentioning

confidence: 69%

Section: Introductionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

TGFBR1 Intralocus Epistatic Interaction as a Risk Factor for Colorectal Cancer

et al. 2012

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“…We appreciate the data and comments provided by Abadie et al (2011) regarding our recent report ‘No association between germline allele-specific expression of TGFBR1 and colorectal cancer risk in Caucasian and Ashkenazi populations' ( Segui et al , 2011 ). They provide new compelling data corroborating our latest findings, which indicate that allele-specific expression (ASE) of TGFBR1 does not confer an increased risk of colorectal cancer (CRC).…”

mentioning

confidence: 99%

Reply: Allelic imbalance of TGFBR1 is not a major contributor to the genetic predisposition to colorectal cancer

et al. 2011

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BRCA1 allele-specific expression in genetic predisposed breast/ovarian cancer

et al. 2016

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Germline allele specific expression (ASE), resulting in a lowered expression of one of the BRCA1 alleles, has been described as a possible predisposition marker in Hereditary Breast or Ovarian Cancer (HBOC), usable for molecular diagnosis in HBOC. The main objective of this prospective case-control study was to compare the proportion of ASE between controls without familial history of breast or ovarian cancer, and HBOC cases without BRCA1 or BRCA2 deleterious mutation. BRCA1 ASE evaluated on three SNPs among controls and HBOC patients without deleterious mutation were assessed by pyrosequencing. The allelic ratios and the proportion of ASE were compared between controls and cases using a Student's t test and a Fisher exact test, respectively. The linearity and reproducibility of the ASE dosage was demonstrated with R > 0.99 and a coefficient of variation below 10 %, and ASE was detected in two positive controls harbouring BRCA1 truncated mutations. In the heterozygote population, composed of 99/264 controls (37.5 %) and 96/227 patients (42.3 %), we detected a 5 % ASE without truncated mutations, in each population. We failed to detect any significant difference of ASE between controls and patients. So far, BRCA1 Allelic specific expression is not usable in routine diagnosis as a possible predisposition marker in HBOC patients except for the detection of truncated mutations.

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Allelic imbalance of the TGFβR1 is not a major contributor to the genetic predisposition to colorectal cancer

Cited by 4 publications

References 6 publications

TGFBR1 Intralocus Epistatic Interaction as a Risk Factor for Colorectal Cancer

TGFBR1 Intralocus Epistatic Interaction as a Risk Factor for Colorectal Cancer

Reply: Allelic imbalance of TGFBR1 is not a major contributor to the genetic predisposition to colorectal cancer

BRCA1 allele-specific expression in genetic predisposed breast/ovarian cancer

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