There were no other common germ line variants identified within the region of the APC gene examined, suggesting that any effect from this region on tumour production is attributable to the c.3920T>A allele.
Comparing the frequencies of the two separate population control groups, the APC I1307K allele is associated with an estimated relative risk of 1.9 for colorectal neoplasia.
Comparing the frequencies of the two separate population control groups, the APC I1307K allele is associated with an estimated relative risk of 1.9 for colorectal neoplasia.
In addition, we did not observe loss of heterozygosity at APC or a somatic mutation near APC I1307K using microdissected tumor DNA from mutation carriers enrolled in the Prostate Cancer Genetic Study.
In addition, we did not observe loss of heterozygosity at APC or a somatic mutation near APC I1307K using microdissected tumor DNA from mutation carriers enrolled in the Prostate Cancer Genetic Study.
Carriers of the I1307K mutation did not appear to differ from noncarriers with regard to the number of neoplasms, patient age at detection, or tumor location within the colon.
Carriers of the I1307K mutation did not appear to differ from noncarriers with regard to the number of neoplasms, patient age at detection, or tumor location within the colon.
It is therefore possible that many APC I1307K carriers with multiple adenomas have a susceptibility to tumours additional to that resulting from the A(8) tract.
Further evidence for the interpretation of the action of I1307K as producing DNA instability is provided by analysing multiple neoplasms from the same person and by showing that these neoplasms have differing patterns of LOH and associated somatic mutations.
It is therefore possible that many APC I1307K carriers with multiple adenomas have a susceptibility to tumours additional to that resulting from the A(8) tract.
Further evidence for the interpretation of the action of I1307K as producing DNA instability is provided by analysing multiple neoplasms from the same person and by showing that these neoplasms have differing patterns of LOH and associated somatic mutations.
I1307K is a low-penetrance genetic variant that indicates a 1.7 relative risk for neoplasia in carriers who have familial carcinoma, clinically equivalent to obtaining a family history of sporadic colorectal neoplasia and promoting early screening.
I1307K is a low-penetrance genetic variant that indicates a 1.7 relative risk for neoplasia in carriers who have familial carcinoma, clinically equivalent to obtaining a family history of sporadic colorectal neoplasia and promoting early screening.
The I1307K mutation represents a novel paradigm for cancer-predisposing genes, as it is associated with moderately increased risk of neoplasia without other associated distinguishing phenotypic features.JAMA.2000;284:857-860
The I1307K mutation represents a novel paradigm for cancer-predisposing genes, as it is associated with moderately increased risk of neoplasia without other associated distinguishing phenotypic features.JAMA.2000;284:857-860
Our findings support the hypothesis that the I1307K mutation is unique to the Ashkenazi Jews, contributes to tumor predisposition in colorectal cancer, and is unrelated to mismatch repair deficiency.
Compared with the frequency in two separate population control groups, the APC I1307K allele is associated with an estimated relative risk of 1.5-1.7 for colorectal neoplasia (both P=.01).