Association of APC I1307K and E1317Q polymorphisms with colorectal cancer among Egyptian subjects

Abdel-Malak, Camelia; Darwish, Hossam; Elsaid, A.; El-Tarapely, Fatma; Elshazli, Rami M.

doi:10.1007/s10689-015-9834-8

Cited by 12 publications

(13 citation statements)

References 47 publications

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“…It is also present among Japanese patients and other Asian populations but it is rare elsewhere 50 . The index case has, in addition, a variant, Ile1307Lys in APC gene, previously described as a risk factor for breast, lung, urologic, pancreatic, and skin cancers 33,34 and has been associated with an increased risk of colorectal cancer among Ashkenazi Jewish, Croatian, and Egyptian patients [35][36][37] . This gene encodes a tumor suppressor protein that acts as an antagonist of the Wnt signaling pathway that regulates crucial aspects of cell fate determination, cell migration, cell polarity, neural patterning and organogenesis during embryonic development.…”

Section: Discussionmentioning

confidence: 99%

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Whole exome sequencing reveals a combination of rare high and low penetrance variants that correlates with familial breast cancer relative risk

Rekaya

Hamdi

Benna

et al. 2020

Preprint

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Background: Genetic risk factors of breast cancer are very heterogeneous and complex. They vary according to the familial relative risk, the age of cancer diagnosis of the index case and the age of the affected relatives.Objectives: We aimed to investigate and identify simultaneously all rare pathogenic and common variants in unrelated BC cases with different relative risk ratios for breast cancer and evaluate the contribution of these variants in genetic susceptibility to breast cancer.Patients and Methods: All frequent mutations in BRCA genes previously identified in Tunisia have been excluded by Sanger sequencing in 42 women affected with high family risk having at least 3 cancer affected related individuals. Two unrelated cases having two different family histories (in terms of different numbers of affected first-degree relatives and young age onset) have been selected for whole exome sequencing. The first family is composed of three sisters F1.1, F1.2 and F1.3 affected at 46, 50, and 32 years old, respectively. The second has only two breast cancer cases, F2.2 and F2.4, affected at late age 61 and 70 years old, respectively, in addition to other 5 members affected by different kinds of cancer. Selected high risk variants were confirmed and segregation analysis was performed using Sanger sequencing. Results and discussion: For F1.1 case, we identified a pathogenic frame-shift loss of function variant in BRCA2 p.Val1283Lysfs. For F2.2 we identified a pathogenic rare variant in OGG1, p.Arg46Gln that co-segregates with a rare non sense variant in BRCA2 p.K3326X, only in the breast cancer affected cases. Moreover, F2.2 patient has 9 other common low penetrant variants in different loci known to represent independently minor, but cumulatively significant, increased risk for breast cancer.Conclusion: Family history and the young age at onset for patient F1.1 correlate with the presence of a rare high penetrant variant (p.Val1283Lysfs) in BRCA2 gene. However, the late age at onset and the less severe phenotype for patient F2.2 are probably the consequence of the presence of a pathogenic variant p.Arg46Gln in OGG1 gene that co-segregate with a low penetrant variant Lys3326X in BRCA2 only in breast cancer cases.

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Section: Discussionmentioning

confidence: 99%

“…Previous studies have shown that it could predict the prevalence of breast, lung, urologic, pancreatic, and skin cancers 33,34 and it has been associated with an increased risk of colorectal cancer among Ashkenazi Jewish, Croatian, and Egyptian patients [35][36][37] .…”

Section: Screening For Rare and Pathogen Variantsmentioning

confidence: 99%

Whole exome sequencing reveals a combination of rare high and low penetrance variants that correlates with familial breast cancer relative risk

Rekaya

Hamdi

Benna

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…The same holds true for colorectal cancer, where there is little population-level data surrounding the prevalence of germline mutations in common cancer susceptibility genes. Germline mutations reported in the literature from African countries suggest that these variants are typically different from those found in HICs and the clinical significance of these mutations remains poorly characterised ( 7 , 21 – 23 ).…”

Section: Molecular Divergence In Cancer Aetiologymentioning

confidence: 99%

Global Inequities in Precision Medicine and Molecular Cancer Research

2018

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Precision medicine based upon molecular testing is heralded as a revolution in how cancer is prevented, diagnosed, and treated. Large efforts across the world aim to conduct comprehensive molecular profiling of disease to inform preclinical models, translational research studies and clinical trials. However, most studies have only been performed in patients from high-income countries. As the burden on non-communicable diseases increases, cancer will become a pressing burden across the world, disproportionately affecting low-middle income settings. There is emerging evidence that the molecular landscape of disease differs geographically and by genetic ancestry, which cannot be explained by environmental factors alone. There is a lack of good quality evidence that characterises the molecular landscape of cancers found in low-middle income countries. As cancer medicine becomes increasingly driven by molecular alterations in high-income settings, low-income settings may become left behind. Further efforts on an international scale must be made by researchers, funders, and policymakers to ensure cancer research addresses disease across the world, so models are not limited to subtypes of disease found in high-income countries. In this review, we discuss differences found in the molecular profiles of tumours worldwide and the implication this has for the future of global cancer care. Finally, we identify several barriers currently limiting progress in this field and innovative solutions, which may address these shortcomings.

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“…A specific germ-line missense mutation, involving transition of T to A at nucleotide 3920 of the APC gene causes the substitution of lysine for isoleucine at codon 1307 [135]. In a recent study, the APC I1307K variant has also been associated with an increased risk of CRC among Ashkenazi Jewish, Croatian, and Egyptian subjects [136–142]. While studies indicate that I1307K substitution predisposes to colorectal cancer, it has also been shown to predict the prevalence of breast, lung, urologic, pancreatic, and skin cancers [143, 144].…”

Section: Polymorphic Variations In Apc and Fen1 Genes That May Affmentioning

confidence: 99%

Interaction between APC and Fen1 during breast carcinogenesis

et al. 2016

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Aberrant DNA base excision repair (BER) contributes to malignant transformation. However, inter-individual variations in DNA repair capacity plays a key role in modifying breast cancer risk. We review here emerging evidence that two proteins involved in BER – adenomatous polyposis coli (APC) and flap endonuclease 1 (Fen1) – promote the development of breast cancer through novel mechanisms. APC and Fen1 expression and interaction is increased in breast tumors versus normal cells, APC interacts with and blocks Fen1 activity in Pol-β-directed LP-BER, and abrogation of LP-BER is linked with cigarette smoke condensate-induced transformation of normal breast epithelial cells. Carcinogens increase expression of APC and Fen1 in spontaneously immortalized human breast epithelial cells, human colon cancer cells, and mouse embryonic fibroblasts. Since APC and Fen1 are tumor suppressors, an increase in their levels could protect against carcinogenesis; however, this does not seem to be the case. Elevated Fen1 levels in breast and lung cancer cells may reflect the enhanced proliferation of cancer cells or increased DNA damage in cancer cells compared to normal cells. Inactivation of the tumor suppressor functions of APC and Fen1 is due to their interaction, which may act as a susceptibility factor for breast cancer. The increased interaction of APC and Fen1 may occur due to polypmorphic and/or mutational variation in these genes. Screening of APC and Fen1 polymorphic and/or mutational variations and APC/Fen1 interaction may permit assessment of individual DNA repair capability and the risk for breast cancer development. Such individuals might lower their breast cancer risk by reducing exposure to carcinogens. Stratifying individuals according to susceptibility would greatly assist epidemiologic studies of the impact of suspected environmental carcinogens. Additionally, a mechanistic understanding of the interaction of APC and Fen1 may provide the basis for developing new and effective targeted chemopreventive and chemotherapeutic agents.

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Association of APC I1307K and E1317Q polymorphisms with colorectal cancer among Egyptian subjects

Cited by 12 publications

References 47 publications

Whole exome sequencing reveals a combination of rare high and low penetrance variants that correlates with familial breast cancer relative risk

Whole exome sequencing reveals a combination of rare high and low penetrance variants that correlates with familial breast cancer relative risk

Global Inequities in Precision Medicine and Molecular Cancer Research

Interaction between APC and Fen1 during breast carcinogenesis

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