%0 Journal Article
%T The intronic G13964C variant in p53 is not a high-risk mutation in familial breast cancer in Australia
%A Anna Marsh
%A Amanda B Spurdle
%A Bruce C Turner
%A Sian Fereday
%A Heather Thorne
%A Gulietta M Pupo
%A Graham J Mann
%A John L Hopper
%A Joseph F Sambrook
%A Georgia Chenevix-Trench
%A Australian Breast Cancer Family Study (ABCFS) and Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFaB)
%J Breast Cancer Research
%D 2001
%I BioMed Central
%R 10.1186/bcr319
%X We genotyped 71 familial breast cancer patients and 143 control individuals for the G13964C variant using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis.Three (4.2%; 95% confidence interval [CI] 0¨C8.9%) G13964C heterozygotes were identified. The variant was also identified in 5 out of 143 (3.5%; 95% CI 0.6¨C6.4%) control individuals without breast cancer or a family history of breast cancer, however, which is no different to the proportion found in familial cases (P = 0.9).The present study would have had 80% power to detect an odds ratio of 4.4, and we therefore conclude that the G13946C polymorphism is not a 'high-risk' mutation for familial breast cancer.Mutations in BRCA1 and BRCA2 account for approximately 50% of breast/ovarian cancer pedigrees with more than four affected cases [1], whereas mutations in PTEN [2], CHK2 [3] and ATM [4] have been reported in a small number of breast cancer families or women with early onset breast cancer. In addition, germ line missense mutations in the p53 gene are associated with Li Fraumeni syndrome, a feature of which is early onset breast cancer [5]. The p53 gene is the most commonly mutated gene in human malignancies and has many important biological functions, including the control of cell cycle checkpoint after DNA damage. Deleterious germ line mutations in the p53 gene are found in less than 1% of all breast cancer patients, suggesting that the contribution of exonic mutations to familial breast cancer risk is small [6,7,8,9,10]. However, mutations in regulatory regions of the gene may affect p53 expression and thereby increase the risk of disease.One candidate for such a mutation is the G13964C variant in intron 6 of the p53 gene, which has been reported in 3 out of 42 patients with hereditary breast cancer (including a CC homozygote affected at age 59 years) but in none of 171 sporadic breast cancer patients (P = 0.0003) [11]. All three patients with the p53 variant had strong f
%K familial breast cancer
%K mutation
%K polymorphism
%K p53
%U http://breast-cancer-research.com/content/3/5/346