Cyclin D1 rare variants in UK multiple adenoma and early-onset colorectal cancer patients

Bonilla, Carolina; Lefèvre, Jérémie H.; Winney, Bruce; Johnstone, Elaine; Tonks, Susan; Colas, Chrystelle; Day, Tammy; Hutnik, Katarzyna; Boumertit, Abdelhamid; Midgley, Rachel; Kerr, David J.; Parc, Yann; Bodmer, W F

doi:10.1038/jhg.2010.144

Cited by 8 publications

(6 citation statements)

References 43 publications

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“…The conclusion is that these variants may well be pathologically relevant, but that the in silico approaches are not yet adequate to detect this. The low-frequency variants (MAF between 1 and 5%) do not appear to influence susceptibility to CRC, as we described earlier for CCND1 36. It is clear that further research is needed to evaluate more fully the role of low-frequency variants in cancer 37.…”

Section: Discussionsupporting

confidence: 54%

Role of rare variants in undetermined multiple adenomatous polyposis and early-onset colorectal cancer

et al. 2012

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Some 15-20% of multiple adenomatous polyposis have no genetic explanation and 20-30% of colorectal cancer (CRC) cases are thought to be due to inherited multifactorial causes. Accumulation of deleterious effects of low-frequency dominant and independently acting variants may be a partial explanation for such patients. The aim of this study was to type a selection of rare and low-frequency variants (o5%) to elucidate their role in CRC susceptibility. A total of 1181 subjects were included (866 controls; 315 cases). Cases comprised UK (n ¼ 184) and French (n ¼ 131) patients with MAP (n ¼ 187) or early-onset CRC (n ¼ 128). Seventy variants in 17 genes were examined in cases and controls. The effect of the variant effect on protein function was investigated in silico. Out of the 70 variants typed, 36 (51%) were tested for association. Twenty-one variants were rare (minor allele frequency (MAF) o1%). Four rare variants were found to have a significantly higher MAF in cases (EXO1-12, MLH1-1, CTNNB1-1 and BRCA2-37, Po0.05) than in controls. Pooling all rare variants with a MAF o0.5% showed an excess risk in cases (odds ratio ¼ 3.2; 95% confidence interval ¼ 1.1-9.5; P ¼ 0.04). Rare variants are important risk factors in CRC and, as such, should be systematically assayed alongside common variation in the search for the genetic basis of complex diseases.

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Section: Discussionsupporting

confidence: 54%

Role of rare variants in undetermined multiple adenomatous polyposis and early-onset colorectal cancer

et al. 2012

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“…Various studies have shown the role of cyclin D1 protein in neoplastic transformation and progression of variety of cancers 28 , 29 . In ISCC of CC, there is discrepancy in the expression of Cyclin D1 as few authors reported the elevated levels 14 , 30 and others reported the decreased levels 14 , 31 .…”

Section: Discussionmentioning

confidence: 99%

Cyclin D1 protein affecting global women’s health by regulating HPV mediated adenocarcinoma of the uterine cervix

Tripathi

Rath

Jawanjal

et al. 2019

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Adenocarcinoma (ADC) of the uterine cervix (UC) is a rare form of cervical cancer (CC) caused due to the infection of Human Papilloma Virus (HPV). Cyclin D1 is one of the downstream targets of aberrantly activated Notch signaling, contribute to the etiology of CC. However, little is known about the role of Cyclin D1 in the modulation of cervical ADC and is controversial. The purpose of this study is to determine the role of Cyclin D1 protein and to elucidate the combined analysis with Notch signaling proteins in HPV associated ADCs of CC. A total of 60 biopsy samples (40 normal and 20 ADCs of CC) were analyzed for the expression of Cyclin D1 in HPV associated ADCs via immunohistochemistry and by immunoblotting. HPV-16 positive ADC patients showed a strong association with the Cyclin D1 expression (p = 0.007). The significant mean difference (p = 0.0001) and the pairwise comparison between Cyclin D1/JAG1 (p = 0.0001), and Cyclin D1/Notch-3 (p = 0.0001) were observed. The above Notch signaling proteins showed their synergistic role in modulating Cyclin D1 which in-turn regulates HPV-16 associated ADC of the uterine cervix (UC), affecting women’s global health.

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“…This polymorphism has been investigated in studies on ovarian, uterine, cervical ( 23 , 24 ) and breast cancer susceptibility alleles in European Caucasians ( 25 , 26 ), however no clear correlations have been identified. Studies into the c.669C>T variant in colorectal cancer in the UK population led to the conclusion that rare variants of the CCND1 gene are risk factors for colorectal cancer, with considerably larger effects compared with common polymorphisms, and as such should be systematically evaluated in susceptibility studies ( 27 , 28 ). The frequency of the c.669C allele in Caucasians is ~96% and the frequency of the minor allele, c.669T, is 4% ( 29 ).…”

Section: Discussionmentioning

confidence: 99%

CCND1 gene polymorphic variants in patients with differentiated thyroid carcinoma

et al. 2014

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Alterations in the CCND1 gene affect the cell cycle and are frequently observed in a variety of cancers. While the most frequent mutations that occur in thyroid tumor tissue have been characterized, the genetic factors that predispose individuals to differentiated thyroid cancer (DTC) remain to be elucidated. The present study examined whether the CCND1 c.723G>A (rs9344; p.Pro241=) and c.669C>T (rs3862792; p.Phe223=) variants have an impact on DTC susceptibility. A cohort consisting of 652 patients diagnosed with DTC were analyzed and comapred with a reference group of 799 subjects from the general population. Pyrosequencing was used as the genotyping technique. In order to determine the statistical significance of differences observed in the genotypic and allelic frequencies between the compared groups, GraphPad Prism 4 was used. At the rs9344 locus in the DTC patients, a higher frequency of allele A [P=0.032; odds ratio (OR), 1.18; 95% confidence interval (CI), 1.014–1.361] and the AA homozygous genotype (P=0.028; OR, 1.41; 95% CI, 1.059–1.989) was observed compared with the control population group. The differences were stronger for papillary carcinomas (OR 1.45; 95% CI, 1.059–1.989), but were not significant in follicular tumors. No statistically significant differences were noted in the frequency of genotypes or alleles at the rs3862792 locus in the examined groups. The present findings indicate that the c.723A variant of the CCDN1 gene may be a susceptibility low penetrance allele in the development of papillary thyroid cancer in the population studied, however it does not impact on multifocality, metastatic ability or age at diagnosis. A cumulative effect of the analyzed CCND1 gene variants was also excluded.

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Cyclin D1 rare variants in UK multiple adenoma and early-onset colorectal cancer patients

Cited by 8 publications

References 43 publications

Role of rare variants in undetermined multiple adenomatous polyposis and early-onset colorectal cancer

Role of rare variants in undetermined multiple adenomatous polyposis and early-onset colorectal cancer

Cyclin D1 protein affecting global women’s health by regulating HPV mediated adenocarcinoma of the uterine cervix

CCND1 gene polymorphic variants in patients with differentiated thyroid carcinoma

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