The Intronic G13964C Variant in P53 is Not a High-risk Mutation in Familial Breast Cancer in Australia

Overview

Journal Breast Cancer Res

Specialty Oncology

Date 2001 Oct 13

PMID 11597326

Citations 5

Authors

A Marsh

A B Spurdle

B C Turner

S Fereday

H Thorne

G M Pupo

G J Mann

J L Hopper

J F Sambrook

G Chenevix-Trench

Affiliations

Soon will be listed here.

Abstract

Background: Mutations in BRCA1 and BRCA2 account for approximately 50% of breast cancer families with more than four affected cases, whereas exonic mutations in p53, PTEN, CHK2 and ATM may account for a very small proportion. It was recently reported that an intronic variant of p53--G13964C--occurred in three out of 42 (7.1%) 'hereditary' breast cancer patients, but not in any of 171 'sporadic' breast cancer control individuals (P = 0.0003). If this relatively frequent occurrence of G13964C in familial breast cancer and absence in control individuals were confirmed, then this would suggest that the G13964C variant plays a role in breast cancer susceptibility.

Method: 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.

Results: Three (4.2%; 95% confidence interval [CI] 0-8.9%) G13964C heterozygotes were identified. The variant was also identified in 5 out of 143 (3.5%; 95% CI 0.6-6.4%) 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).

Conclusion: 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.

Citing Articles

P53 gene polymorphisms and breast cancer risk in Arab women.

Alawadi S, Ghabreau L, Alsaleh M, Abdulaziz Z, Rafeek M, Akil N Med Oncol. 2010; 28(3):709-15.

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Intronic TP53 Germline Sequence Variants Modify the Risk in German Breast/Ovarian Cancer Families.

Liu X, Sinn H, Ulmer H, Scott R, Hamann U Hered Cancer Clin Pract. 2010; 2(3):139-45.

PMID: 20233468 PMC: 4392522. DOI: 10.1186/1897-4287-2-3-139.

Polymorphisms in p53 and the p53 pathway: roles in cancer susceptibility and response to treatment.

Hrstka R, Coates P, Vojtesek B J Cell Mol Med. 2009; 13(3):440-53.

PMID: 19379143 PMC: 3822507. DOI: 10.1111/j.1582-4934.2008.00634.x.

Analysis of cancer risk and BRCA1 and BRCA2 mutation prevalence in the kConFab familial breast cancer resource.

Mann G, Thorne H, Balleine R, Butow P, Clarke C, Edkins E Breast Cancer Res. 2006; 8(1):R12.

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The R72P P53 mutation is associated with familial breast cancer in Jewish women.

Ohayon T, Gershoni-Baruch R, Papa M, Distelman Menachem T, Eisenberg Barzilai S, Friedman E Br J Cancer. 2005; 92(6):1144-8.

PMID: 15756275 PMC: 2361953. DOI: 10.1038/sj.bjc.6602451.

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