The APC p.I1307K polymorphism is a significant risk factor for CRC in average risk Ashkenazi Jews

Boursi, Ben; Sella, Tal; Liberman, Eliezer; Shapira, Shiran; David, Menachem P.; Kazanov, Diana; Arber, Nadir; Kraus, Sarah

doi:10.1016/j.ejca.2013.06.040

Cited by 44 publications

(35 citation statements)

References 28 publications

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“…17 A subgroup analysis found that the prevalence of the I1307K polymorphism in individuals of Ashkenazi Jewish descent was 10.1% and the adjusted OR was 1.75 (95% CI, 1.26-2.45). 17 A meta-analysis including 40 studies showed that compared with carriers of wild-type I1307K, individuals of Ashkenazi Jewish descent who carried the I1307K polymorphism had a significantly increased risk of colorectal neoplasia, with a pooled OR of 2.17 (95% CI, 1.64-2.86). 20 Some studies have identified the I1307K polymorphism in the APC gene in individuals of non-Ashkenazi Jewish and Arabic descent, although the prevalence is higher in individuals of Ashkenazi Jewish descent.…”

Section: Apc I1307k Mutationmentioning

confidence: 99%

“…16 There is well-established evidence that the I1307K polymorphism in the APC gene, which occurs in approximately 6% to 8% of individuals of Ashkenazi Jewish decent, predisposes carriers to CRC. [17][18][19][20][21] In an analysis of 3,305 individuals from Israel who underwent colonoscopic examinations, 8% were identified as carriers of the I1307K polymorphism, and the overall adjusted odds ratio (OR) for colorectal neoplasia among carriers was 1.51 (95% CI, 1.16-1.98). 17 A subgroup analysis found that the prevalence of the I1307K polymorphism in individuals of Ashkenazi Jewish descent was 10.1% and the adjusted OR was 1.75 (95% CI, 1.26-2.45).…”

Section: Apc I1307k Mutationmentioning

confidence: 99%

“…[17][18][19][20][21] In an analysis of 3,305 individuals from Israel who underwent colonoscopic examinations, 8% were identified as carriers of the I1307K polymorphism, and the overall adjusted odds ratio (OR) for colorectal neoplasia among carriers was 1.51 (95% CI, 1.16-1.98). 17 A subgroup analysis found that the prevalence of the I1307K polymorphism in individuals of Ashkenazi Jewish descent was 10.1% and the adjusted OR was 1.75 (95% CI, 1.26-2.45). 17 A meta-analysis including 40 studies showed that compared with carriers of wild-type I1307K, individuals of Ashkenazi Jewish descent who carried the I1307K polymorphism had a significantly increased risk of colorectal neoplasia, with a pooled OR of 2.17 (95% CI, 1.64-2.86).…”

Section: Apc I1307k Mutationmentioning

confidence: 99%

See 2 more Smart Citations

NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Colorectal, Version 3.2017

Gupta¹,

Provenzale²,

Regenbogen³

et al. 2017

J Natl Compr Canc Netw

146

163

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Section: Apc I1307k Mutationmentioning

confidence: 99%

Section: Apc I1307k Mutationmentioning

confidence: 99%

Section: Apc I1307k Mutationmentioning

confidence: 99%

See 1 more Smart Citation

NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Colorectal, Version 3.2017

Gupta¹,

Provenzale²,

Regenbogen³

et al. 2017

J Natl Compr Canc Netw

146

163

View full text Add to dashboard Cite

“…This APC mutation does not cause traditional familial adenomatous polyposis, but rather, has been shown to 6 increase risk for colon cancer, and the NCCN recommends increased surveillance for carriers of this specific 7 mutation (Boursi et al 2013;Liang et al 2013;National Comprehensive Cancer Network 2016).…”

mentioning

confidence: 99%

“…http://dx.doi.org/10.1101/151225 doi: bioRxiv preprint first posted online Jun. 18, 2017; moderate risk allele for colon cancer, and has issued screening guidelines for heterozygous 1 carriers of this mutation (Boursi et al 2013;Liang et al 2013; National Comprehensive 2 Cancer Network 2016). In total, 12 of the 70 individuals in the cohort (17%) had medically 3 actionable likely pathogenic or pathogenic variants identified (see Table 3 for the complete 4 list of actionable variants).…”

mentioning

confidence: 99%

High Frequency Actionable Pathogenic Exome Mutations in an Average-Risk Cohort

Rego

Dagan‐Rosenfeld

Zhou

et al. 2017

Preprint

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Prevalence and Spectrum of Germline Cancer Susceptibility Gene Mutations Among Patients With Early-Onset Colorectal Cancer

et al. 2017

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IMPORTANCE Hereditary cancer syndromes infer high cancer risks and require intensive cancer surveillance, yet the prevalence and spectrum of these conditions among unselected patients with early-onset colorectal cancer (CRC) is largely undetermined. OBJECTIVE To determine the frequency and spectrum of cancer susceptibility gene mutations among patients with early-onset CRC. DESIGN, SETTING, AND PARTICIPANTS Overall, 450 patients diagnosed with colorectal cancer younger than 50 years were prospectively accrued from 51 hospitals into the Ohio Colorectal Cancer Prevention Initiative from January 1, 2013, to June 20, 2016. Mismatch repair (MMR) deficiency was determined by microsatellite instability and/or immunohistochemistry. Germline DNA was tested for mutations in 25 cancer susceptibility genes using next-generation sequencing. MAIN OUTCOMES AND MEASURES Mutation prevalence and spectrum in patients with early-onset CRC was determined. Clinical characteristics were assessed by mutation status. RESULTS In total 450 patients younger than 50 years were included in the study, and 75 gene mutations were found in 72 patients (16%). Forty-eight patients (10.7%) had MMR-deficient tumors, and 40 patients (83.3%) had at least 1 gene mutation: 37 had Lynch syndrome (13, MLH1 [including one with constitutional MLH1 methylation]; 16, MSH2; 1, MSH2/monoallelic MUTYH; 2, MSH6; 5, PMS2); 1 patient had the APC c.3920T>A, p.I1307K mutation and a PMS2 variant; 9 patients (18.8%) had double somatic MMR mutations (including 2 with germline biallelic MUTYH mutations); and 1 patient had somatic MLH1 methylation. Four hundred two patients (89.3%) had MMR-proficient tumors, and 32 patients (8%) had at least 1 gene mutation: 9 had mutations in high-penetrance CRC genes (5, APC; 1, APC/PMS2; 2, biallelic MUTYH; 1, SMAD4); 13 patients had mutations in high- or moderate-penetrance genes not traditionally associated with CRC (3, ATM; 1, ATM/CHEK2; 2, BRCA1; 4, BRCA2; 1, CDKN2A; 2, PALB2); 10 patients had mutations in low-penetrance CRC genes (3, APC c.3920T>A, p.I1307K; 7, monoallelic MUTYH). Importantly, 24 of 72 patients (33.3%) who were mutation positive did not meet established genetic testing criteria for the gene(s) in which they had a mutation. CONCLUSIONS AND RELEVANCE Of 450 patients with early-onset CRC, 72 (16%) had gene mutations. Given the high frequency and wide spectrum of mutations, genetic counseling and testing with a multigene panel could be considered for all patients with early-onset CRC.

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The APC p.I1307K polymorphism is a significant risk factor for CRC in average risk Ashkenazi Jews

Cited by 44 publications

References 28 publications

NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Colorectal, Version 3.2017

NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Colorectal, Version 3.2017

High Frequency Actionable Pathogenic Exome Mutations in an Average-Risk Cohort

Prevalence and Spectrum of Germline Cancer Susceptibility Gene Mutations Among Patients With Early-Onset Colorectal Cancer

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