No association of the I1307K APC allele with ovarian cancer risk in Ashkenazi Jews.
Familial adenomatous polyposis is a dominantly inherited colon cancer syndrome associated with germ-line mutations in the APC tumor suppressor gene. An APC gene sequence alteration, the I1307K allele, occurs in 6% of the Ashkenazi Jewish population and is reported to double the risk for colorectal cancer. We screened a population of 190 Ashkenazi women who were diagnosed with epithelial ovarian carcinoma for the I1307K variant and measured the effect of this allele on the risk for cancer development in their first-degree relatives. We identified the I1307K allele in 7.9% (15 of 190) of our ovarian cancer cases. The average age of ovarian cancer diagnosis in carriers of the I1307K allele (57.5 years) was not statistically different than the age for noncarriers (56.4 years; P = 0.70). Among the 1087 first-degree relatives, there were 23 cases of colorectal cancer; 3 of 100 relatives of probands with the I1307K allele (3.0%) had a history of colorectal cancer versus 20 of 987 relatives of probands without the I1307K allele (2.1%; relative risk, 1.48; 95% confidence interval, 0.45-4.88; P = 0.462). Relatives of the I1307K carriers had a risk of 38.0% for developing any cancer to age 80, similar to the risk for relatives of noncarriers of the I1307K allele (42.1%; P = 0.86). The average age of diagnosis of cancer of any type was not different between relatives of carriers (59.0 years) and noncarriers (60.4 years). In the Ashkenazi Jewish population, the I1307K allele is unlikely to increase the risk of ovarian cancer or of cancer in general.
Women's College Hospital, The Centre for Research in Women's Health, Toronto, Ontario, Canada.
J
J
Abrahamson
R
R
Moslehi
D
D
Vesprini
B
B
Karlan
D
D
Fishman
D
D
Smotkin
Y
Y
Ben David
H
H
Biran
A
A
Fields
J S
JS
Brunet
S A
SA
Narod
D014408:Biomarkers, Tumor / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics; D005260:Female; D017491:Genes, APC / Q000235:genetics*; D006801:Humans; D007585:Jews; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000208:ethnology / Q000235:genetics*; D010375:Pedigree; D012307:Risk Factors
D014408:Biomarkers, Tumor