The I1307K APC mutation in a high‐risk clinic setting: a follow‐up study

Abstract

While the I1307K APC mutation clearly confers an increased lifetime risk for colorectal cancer, there is a paucity of data on the natural history of colonic neoplasia in symptomatic and asymptomatic mutation carriers. In this study, 51 Jewish I1307K APC mutation carriers were identified in a high-risk familial cancer clinic over a 4-year period, of whom 29 (56.8%) (four males and 25 females) were successfully telephone interviewed for 0.5-5 years (mean 2.4 +/- 1.4) after initial genetic testing. Of these 29 cases, one individual was diagnosed with colon cancer at the age of 45 years, five had adenomatous polyps (mean number of polyps = 1.8), 11 had breast cancer (mean age at diagnosis 49.5 +/- 10.5 years), and 12 were asymptomatic, at the time of the testing. During the follow-up period, new colonic polyps were diagnosed in three mutation carriers, two with previously diagnosed colon cancer and polyps and only one of the asymptomatic mutation carriers, and two additional previously affected patients had new cancer diagnoses: gastric cancer and melanoma. From this descriptive study, it seems that the short-term risk for colonic polyps in I1307K APC mutation is low, primarily affecting patients with previously diagnosed colon tumors.

Congenital hypertrophy of the retinal pigment epithelium (CHRPE) in familial colorectal cancer

“…3c). A second patient had the common Jewish I1307 K polymorphism which is weakly pathogenic [30]; this patient had a normal retinal examination.…”

Presence of a TA Haplotype in the APC Gene Containing the Common 1822 Polymorphism and Colorectal Adenoma

“…Furthermore, there seems to be a protective role for synonymous polymorphic changes when present with particular nonsynonymous polymorphisms. Whereas previous studies have shown the value of individual SNP analysis in assessing the odds of disease (7,(9)(10)(11)(12)(13), our work and that of Cui and colleagues (29) suggest that evaluating allele structure is critical in the understanding of the role of APC polymorphic variation and colorectal adenoma and perhaps susceptibility to cancer. Further evaluation of these findings would serve to expand the understanding of the role of these polymorphisms and haplotypes in the etiology of colorectal cancer.…”

“…The results from our study are intriguing because they support previous conclusions that these common and rare allele variants of APC likely influence colorectal carcinogenesis (7,8,22). A number of studies support the importance of variation in APC on colorectal adenoma with weak to no association with colorectal cancer (9,10,12,13,15,17,18,23). These data suggest that modest acting variants might act as predisposing variants for adenoma development but are insufficient alone as risk factors for cancer.…”

“…However, results from other studies are less informative with the majority observing no difference in risk of colorectal adenomas or colorectal cancer by the 1307 genotype (9)(10)(11)(12)(13)(14)(15). The frequency of the 1307K polymorphism is highest in Ashkenazi Jewish populations (f6%; refs.…”

Single nucleotide polymorphisms and colorectal neoplasia risk: Updates and impact

“…The authors reported similar ages of CRC and adenoma onset in I1307K carriers and noncarriers, but estimated a greater than twofold CRC risk increase in I1307K carriers (OR, 2.24; 95% CI, 1.24-4.05). During prospective followup on a subset of carriers (n = 29; mean follow-up, 2.4 ± 1.4 years) new adenomas were detected in three individuals (two had previously been diagnosed with CRC and polyps) [49]. Although this work is one of the fi rst to prospectively follow I1307K carriers, health information on adenoma and CRC diagnosis was obtained primarily by patient report and was not directly diagnosed or collected by the investigators.…”