The effect of the I1307K APC polymorphism on the clinicopathological features and natural history of breast cancer

The I1307K polymorphism in APC has been found to predispose to colorectal c ancer in Ashkenazi Jews, and has recently been associated with an increased risk for breast cancer in the same population. in that study. we genotyped 205 paraffin-embedded breast cancers from Ashkenazi Jewish women diagnosed below the age of 65. We now present an extended analysis, with clinicopath ological correlations between carriers of I1307K and non-carriers. Twenty-f our of 209 cases (11.5%, 95% confidence interval 7.5-16.6) were found to ca rry the I1307K polymorphism. When stratifying the data by other relevant cl inicopathological variables, we observed no association between the presenc e of this polymorphism and age at diagnosis (P = 0.52), grade (P = 0.074), tumour size (P = 0.99), lymph node status (P = 0.82), oestrogen receptor st atus (P = 0.23) or P53 immunoreactivity (P = 0.80). The breast-cancer speci fic 5-year survival for women with I1307 K polymorphism was 88.9% compared with 81.6% in women without I1307K (P = 0.34). Using microdissected samples and direct sequencing, no somatic mutations were observed in any of the 24 I1307K-positive cases. Single-strand conformation analysis of 158 of the I 1307K-negative breast cancers that were available far study revealed no mob ility shifts. We conclude that the presence of the I1307K polymorphism does not appear to be associated with any particular clinicopathological featur e of breast cancer and importantly. does not affect the prognosis. (C) 1999 cancer Research Campaign.