Adenomatous polyposis coli I1307K mutation in Jewish patients with different ethnicity

Abstract

BACKGROUND A new mutation, I1307K, recently was reported in the adenomatous polyposis coli (APC) gene. This mutation was found to be predominant in Ashkenazi Jews, creating a hypermutable area and predisposing the development of carcinoma. The objective of the current study was to estimate the prevalence of this mutation in several of the ethnic groups that comprise the Israeli population and to elucidate the clinical features of the mutation carriers with colorectal carcinoma (CRC). METHODS A total of 111 consecutive CRC patients were evaluated and their medical history and clinical data recorded. The general population (298 Ashkenazim and 189 Yemenites) also was tested for the presence of this mutation. Mutation screening was performed using both the polymerase chain reaction‐based amplification refractory mutation system and a commercial APC kit. RESULTS Of the total of 111 CRC patients, 15 (13.5%) carried the I1307K mutation and 26 of 487 subjects from the general population (5.3%) carried the I1307K mutation (P = 0.004). Among the 71 Ashkenazi CRC patients there were 12 carriers (16.9%) whereas 17 of the 298 Ashkenazi Jewish general population (5.7%) carried the mutation (P = 0.004). Of the 4 CRC patients of Yemenite origin, 3 carried the mutation and 9 carriers were found among 189 subjects in the general Yemenite population (4.7%) (P = 0.0007). None of the 34 Sepharadic or 2 Arab CRC patients carried the APC I1307K allele. Late age at diagnosis (64.6 years ± 10.0, which is similar to that of the noncarriers), mostly right‐sided tumors, and moderate to good differentiation constituted the phenotype of the mutation carriers. CONCLUSIONS The authors believe the findings of the current study broaden the known spectrum of ethnic groups in which the APC I1307K mutation is prevalent. The phenotype of the mutation carrier CRC patients does not conform to the expected familial pattern of germline mutations. The phenotype and the differential incidence rate of CRC among APC I1307K carriers of various ethnic groups suggest low penetrance. Cancer 2000;88:755–60. © 2000 American Cancer Society.

Phenotypic characteristics of colo-rectal cancer in I1307K APC germline mutation carriers compared with sporadic cases

“…This finding is counter-intuitive, as the prevailing paradigm of cancer susceptibility genes predicts that mutation carriers will exhibit early age at onset, and have a personal or a family history of cancer more frequently than sporadic cases. The findings of a similar age at onset and family history of cancer in mutation carriers and non-carriers reported herein are consistent with another study (Drucker et al, 2000). Taken together with the reports that adenomatous colonic polyps were not more prevalent in I1307K mutation carriers compared with non-carriers (Syngal et al, 2000;Stern et al, 2001), these findings imply that the I1307K APC mutation confers a moderate increased lifetime risk for CRC (Woodage et al, 1998;Gryfe et al, 1999).…”

“…In fact, we previously showed that the mutation probably represents a founder mutation in Jewish individuals (Patael et al, 1998), as was also confirmed by other investigators (Woodage et al, 1998). Drucker et al (2000), reported that the I1307K mutation was detected in 3/4 Yemenite Jewish individuals, whereas in the present study this mutation could not be detected in any of 18 Yemenite Jews with CRC. This discrepancy cannot be logically settled, until more individuals of Yemenite extraction are tested.…”

“…Mutation carriers had a more advanced disease stage, in line with the observations from another study from Israel (Drucker et al, 2000). Yet, several differences exist between the data presented herein and the study by Drucker and co-workers (2000).…”

“…Studies involving I1307K carriers have shown a moderate increase (up to 2-fold) in colon cancer risk (Laken et al, 1997;Woodage et al, 1998;Rozen et al, 1999;Gryfe et al, 1999). This specific polymorphism was considered to be limited to Ashkenazi Jews (Laken et al, 1997;Prior et al, 1999), but it was also reported in Jewish individuals of non-Ashkenazi origin (Rozen et al, 1999;Patael et al, 1999;Drucker et al, 2000;Shtoyerman et al, 2001), as well as non-Jewish individuals (Yuan et al, 1998;Nathanson et al, 1999). Yet, the rate of this mutation in the Jewish Ashkenazi population (5-7%) (Laken et al, 1997;Woodage et al, 1998) and among patients with familial CRC (up to 28%) (Laken et al, 1997) facilitates large-scale analysis of this mutation in unselected Jewish sub-populations.…”

APC I1307K and the E1317Q variants are not present in Chinese colorectal cancer patients

“…7 This variant has been reported exclusively in the Ashkenazi 2,7,8 and Yemenite Jewish populations. 9 Like the I1307K variant, the E1317Q variant results in a charge difference from a single amino acid change. 6 As opposed to the I1307K variant, this variant is present in both Ashkenazi Jewish and non-Ashkenazi Jewish Caucasian populations, and is believed to predispose to colonic adenomas and carcinomas.…”