The TGFBR1*6A allele is not associated with susceptibility to colorectal cancer in a Spanish population: a case-control study

Castillejo, Adela; Mata-Balaguer, Trinidad; Montenegro, Paola; Ochoa, Enrique; Lázaro, Rafael; Martínez-Cantó, Ana; Castillejo, M.I.; Guarinós, Carla; Barbera, V.; Guillén‐Ponce, Carmen; Carrato, Alfredo; Soto, José Luís

doi:10.1186/1471-2407-9-193

Cited by 13 publications

(11 citation statements)

References 15 publications

(28 reference statements)

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“…The follow‐up time was up to 16 years after diagnosis, allowing analysis of long‐term survival. The proportion of women (56.5%) in our study was slightly higher than in other studies about the effects of the TGB1 pathway genes on the risk of CRC; however, we did not observe any gender‐specific differences in genotype distribution in concordance with the previous studies (Pasche et al,1999; Sparks et al,2004; Berndt et al,2007; Saltzman et al,2008; Castillejo et al,2009). With our sample size of 308 patients with CRC and 585 controls, we had a limited power to detect the relatively low ORs observed for common SNPs in the recent genome‐wide association studies (GWASs) (Easton and Eeles,2008; Houlston et al,2008).…”

Section: Discussionsupporting

confidence: 88%

Polymorphisms in the transforming growth factor beta 1 pathway in relation to colorectal cancer progression

Försti

Wagner

et al. 2009

Genes Chromosomes & Cancer

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Transforming growth factor beta1 (TGFB1) acts as a growth inhibitor of normal colonic epithelial cells, however, as a tumor promoter of colorectal cancer (CRC) cells. To explore the association between genetic polymorphisms in the TGFB1 pathway and CRC susceptibility and clinical outcome, we carried out a case-control study on a Swedish population of 308 CRC cases and 585 age- and gender-matched controls. The cases were sampled prospectively and had up to 16 years follow-up, making the study material particularly suitable for survival analysis. On the basis of their reported or predicted functional effect, nine single-nucleotide polymorphisms (TGFB1: Leu10Pro; TGFBR1: 9A/6A and IVS7G+24A; FURIN: C-229T; THBS1: T+42C; LTBP1L: C-256G; LTBP4: T-893G and Thr750Ala; BAMBI: T-779A) were selected for genotyping. We evaluated the associations between genotypes and CRC and Dukes' stage. Survival probabilities were compared between different subgroups. The observed statistically significant associations included a decreased CRC risk for TGFBR1 IVS7G+24A minor allele carriers (odds ratio (OR): 0.72, 95% confidence interval (CI): 0.53-0.97), less aggressive tumors with Dukes' stage A+B for carriers of LTBP4 Thr750Ala and BAMBI T-779A minor alleles (OR: 0.58, 95%CI: 0.36-0.93 and OR: 0.51, 95%CI: 0.29-0.89, respectively) and worse survival for FURIN C-229T heterozygotes (hazard ratio: 1.63, 95%CI: 1.08-2.46). As this is the first study about the influence of the polymorphisms in the TGFB1 pathway on CRC progression, further studies in large independent cohorts are warranted.

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Section: Discussionsupporting

confidence: 88%

Polymorphisms in the transforming growth factor beta 1 pathway in relation to colorectal cancer progression

Försti

Wagner

et al. 2009

Genes Chromosomes & Cancer

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“…There is wide geographical variation in incidence with rates varying 8-fold (colon cancer) and 6-fold (rectal cancer) in both sexes worldwide[1]. In this sense, Spain is one of the countries with the highest incidence of CRC, and taking into account both sexes, it was the most frequent cancer diagnosed in 2018 with 13.7% of newcancer cases[2] and is the main cause of cancer related deaths [3]. Considering the magnitude of the problem, the use of screening tests for early detection and effective treatment of CRC during the initial stages would have a significant impact on public health.…”

Section: Introductionmentioning

confidence: 99%

Single nucleotide polymorphisms associated with susceptibility for development of colorectal cancer: Case-control study in a Basque population

et al. 2019

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Given the significant population diversity in genetic variation, we aimed to investigate whether single nucleotide polymorphisms (SNPs) previously identified in studies of colorectal cancer (CRC) susceptibility were also relevant to the population of the Basque Country (North of Spain). We genotyped 230 CRC cases and 230 healthy controls for 48 previously reported CRC-susceptibility SNPs. Only the rs6687758 in DUPS10 exhibited a statistically significant association with CRC risk based on the crude analysis. The rs6687758 AG genotype conferred about 2.13-fold increased risk for CRC compared to the AA genotype. Moreover, we found significant associations in cases between smoking status, physical activity, and the rs6687758 SNP. The results of a Genetic Risk Score (GRS) showed that the risk alleles were more frequent in cases than controls and the score was associated with CRC in crude analysis. In conclusion, we have confirmed a CRC susceptibility locus and the existence of associations between modifiable factors and the rs6687758 SNP; moreover, the GRS was associated with CRC. However, further experimental validations are needed to establish the role of this SNP, the function of the gene identified, as well as the contribution of the interaction between environmental factors and this locusto the risk of CRC.

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“…al recently published a study of *6A risk and osteosarcoma for a Chinese patient population in which no significant association was discovered [42]. Castillejo et al reported results that suggest that the TGFBR1* 6A allele does not confer an increased risk of colorectal cancer in the Spanish population [43]. A small study in lung cancer did not show any significant increase in risk for TGFBR1* 6A mutation carriers [44].…”

Section: Characterization Of Tgfbr1*6amentioning

confidence: 99%

TGFBR1 Signaling and Breast Cancer

Moore-Smith

Pasche

2011

J Mammary Gland Biol Neoplasia

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Over the past decade mutations discovered in genes such as BRCA1, BRCA2, TP53 and PTEN, have emerged as high-penetrance susceptibility genes and are clinically relevant for determination of breast cancer risk. Genetic counseling and subsequent screening for mutations and gene rearrangement has improved patient outcome through early detection and prophylactic interventions in patients with familial breast cancer syndromes. However, these high-penetrance genes only account for a small fraction of the hereditary linked breast cancers. It is currently believed that low-penetrance susceptibility alleles and/or environmental factors may play an important role in the remaining cases. TGFBR1*6A (*6A) is a common hypomorphic variant of the type I TGF-β receptor gene (TGFBR1) that has been associated with risk for several forms of cancer, in particular breast cancer. Several epidemiological studies have suggested that patients who carry the *6A allele have an increased risk of breast cancer. Furthermore, functional analysis suggests that this mutation alters TGF-β signaling and promotes tumorigenesis. Although a decade of research has provided basic information in regards to the prevalence of this mutation in several cancer types and populations the molecular underpinning of its functional effects are poorly understood. A better understanding of the molecular mechanism of TGFBR1 signaling in breast cancer may have an impact on breast cancer risk assessment and breast cancer prevention.

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The TGFBR1*6A allele is not associated with susceptibility to colorectal cancer in a Spanish population: a case-control study

Cited by 13 publications

References 15 publications

Polymorphisms in the transforming growth factor beta 1 pathway in relation to colorectal cancer progression

Polymorphisms in the transforming growth factor beta 1 pathway in relation to colorectal cancer progression

Single nucleotide polymorphisms associated with susceptibility for development of colorectal cancer: Case-control study in a Basque population

TGFBR1 Signaling and Breast Cancer

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