rs1801155

badMag 6.5

This is a protein-altering variant in the APC gene.

Key Literature Trait Associations

Colorectal Cancer Risk

The APC I1307K variant (c.3920T>A, p.Ile1307Lys) creates a hypermutable poly-A repeat (A8 instead of A3TA4) prone to somatic frameshift during DNA replication, meaning it does not directly inactivate APC but renders the gene susceptible to subsequent somatic mutations. Carriers have approximately 1.5–2× the average risk of colorectal cancer. The variant is present in roughly 6–10% of Ashkenazi Jewish individuals and is considerably rarer in other populations. Carriers should discuss colonoscopy surveillance with their physician.

Liang J et al. “APC polymorphisms and the risk of colorectal neoplasia: a HuGE review and meta-analysis.” American Journal of Epidemiology (2013)

Allele A

OR 2.17

p —

Meta-analysis

Ashkenazi Jewish

Boursi B et al. “The APC p.I1307K polymorphism is a significant risk factor for CRC in average risk Ashkenazi Jews.” European Journal of Cancer (oxford, England : 1990) 49(17):3680-3685 (2013)

Allele A

OR 1.75

p 1.0e-6

Preliminary work

Forkosh E et al. “Ashkenazi Jewish and Other White APC I1307K Carriers Are at Higher Risk for Multiple Cancers.” Cancers (2022)

Allele A

OR 1.95

p —

N 213,133

Preliminary work

Ashkenazi Jewish and non-Ashkenazi White

Yurgelun MB et al. “Cancer Susceptibility Gene Mutations in Individuals With Colorectal Cancer.” Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology (2017)

Allele A

OR —

p —

N 1,058

Preliminary work

multi-ancestry

Valle L et al. “Position statement of the International Society for Gastrointestinal Hereditary Tumours (InSiGHT) on APC I1307K and cancer risk.” Journal of Medical Genetics (2023)

Allele A

OR —

p —

Candidate gene study

Ashkenazi Jewish

Breast cancer

APC I1307K has been associated with elevated breast cancer risk, primarily in female Ashkenazi Jewish carriers and non-Ashkenazi white women. A large 2016 study of 13,013 healthy subjects and 1,611 cancer patients found an overall adjusted OR of 2.53 (p<0.0001) for any cancer in I1307K carriers, with breast cancer showing increased prevalence among female carriers. A 2022 registry study found OR=1.73 for breast cancer in non-Ashkenazi white female carriers. Evidence is more limited than for colorectal cancer and routine enhanced screening for breast cancer in I1307K carriers is not yet universally recommended.

Forkosh E et al. “Ashkenazi Jewish and Other White APC I1307K Carriers Are at Higher Risk for Multiple Cancers.” Cancers (2022)

Allele A

OR 1.73

p —

N 213,133

Preliminary work

non-Ashkenazi White

Leshno A et al. “The APC I1307K allele conveys a significant increased risk for cancer.” International Journal of Cancer (2016)

Allele A

OR 2.53

p 1.0e-4

N 14,624

Preliminary work

Ashkenazi Jewish

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ClinVar annotation

Risk Factor

55 submitters91 publications

; Breast cancer, susceptibility to; not provided; Familial adenomatous polyposis 1; not specified; Hereditary cancer-predisposing syndrome; Familial multiple polyposis syndrome; Colorectal cancer, susceptibility to; Carcinoma of colon; Colorectal cancer; APC-Associated Polyposis Disorders; Breast carcinoma; Familial colorectal cancer; Diffuse midline glioma, H3 K27-altered

View on ClinVar →

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Research that mentions this SNP (1)

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

AssociationN=450Pearlman R. et al.(2017)· JAMA Oncology

A prospective cohort study of 450 patients with early-onset colorectal cancer (diagnosed before age 50) identified 72 patients (16%) with pathogenic mutations in cancer susceptibility genes, including 37 with Lynch syndrome (MLH1, MSH2, MSH6, PMS2). The study found that multigene panel testing identified mutations in 33.3% of patients who did not meet conventional genetic testing criteria, suggesting that broad multigene panel testing should be considered for all early-onset CRC patients.

Traits studied:Breast cancerColorectal cancerEarly-onset colorectal cancerFamilial adenomatous polyposisHereditary breast-ovarian cancerJuvenile polyposis syndromeLynch syndromeMUTYH-associated polyposisMelanomaPancreatic cancer

rs1801155

Key Literature Trait Associations

Colorectal Cancer Risk

Breast cancer

ClinVar annotation

Research that mentions this SNP (1)

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