✦ LIBER ✦

Lymphocyte radiosensitivity in BRCA1 and BRCA2 mutation carriers and implications for breast cancer susceptibility

✍ Scribed by Julian Barwell; Laurent Pangon; Anne Georgiou; Ian Kesterton; Caroline Langman; Audrey Arden-Jones; Elizabeth Bancroft; Ashi Salmon; Imogen Locke; Zsofia Kote-Jarai; Joanna R. Morris; Ellen Solomon; Jonathan Berg; Zoe Docherty; Richard Camplejohn; Rosalind Eeles; Shirley V. Hodgson

Publisher: John Wiley and Sons
Year: 2007
Tongue: French
Weight: 336 KB
Volume: 121
Category: Article
ISSN: 0020-7136
DOI: 10.1002/ijc.22915

No coin nor oath required. For personal study only.

✦ Synopsis

Abstract

There is conflicting evidence as to whether individuals who are heterozygous for germ‐line BRCA1 or BRCA2 mutations have an altered phenotypic cellular response to irradiation. To investigate this, chromosome breakage and apoptotic response were measured after irradiation in peripheral blood lymphocytes from 26 BRCA1 and 18 BRCA2 mutation carriers without diagnosed breast cancer, and 38 unaffected age, ethnically and sex‐matched controls. To assess the role of BRCA1 and BRCA2 in homologous recombination, an S phase enrichment chromosome breakage assay was used. BrdUrd incorporation studies allowed verification of the correct experimental settings. We found that BRCA1 mutation carriers without cancer had increased chromosome breaks as well as breaks and gaps per cell post irradiation using the classical G2 assay (p = 0.01 and 0.004, respectively) and the S phase enrichment assay (p = 0.01 and 0.01, respectively) compared to age‐matched unaffected controls. BRCA2 mutation carriers without cancer had increased breaks as well as breaks and gaps per cell post irradiation using the S phase enrichment assay (p = 0.045 and 0.012, respectively). No difference was detected using the G2 assay (p = 0.88 and 0.40 respectively). BRCA1 and BRCA2 mutation carriers had normal cell cycle kinetics and apoptotic response to irradiation compared to age‐matched controls. Our results show a demonstrable impairment in irradiation induced DNA repair in women with heterozygous germline BRCA1 and BRCA2 mutations prior to being diagnosed with breast cancer. © 2007 Wiley‐Liss, Inc.

📜 SIMILAR VOLUMES

Ovarian cancer susceptibility alleles an

Ovarian cancer susceptibility alleles and risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers

✍ Susan J. Ramus; Antonis C. Antoniou; Karoline B. Kuchenbaecker; Penny Soucy; Jon 📂 Article 📅 2012 🏛 John Wiley and Sons 🌐 English ⚖ 361 KB

Germline mutations in BRCA1 and BRCA2 are associated with increased risks of breast and ovarian cancer. A genome-wide association study (GWAS) identified six alleles associated with risk of ovarian cancer for women in the general population. We evaluated four of these loci as potential modifiers of

Coffee consumption and breast cancer ris

Coffee consumption and breast cancer risk among BRCA1 and BRCA2 mutation carriers

✍ André Nkondjock; Parviz Ghadirian; Joanne Kotsopoulos; Jan Lubinski; Henry Lynch 📂 Article 📅 2005 🏛 John Wiley and Sons 🌐 French ⚖ 91 KB 👁 1 views

## Abstract Although there are several plausible biologic mechanisms whereby coffee consumption might influence the risk of breast cancer, epidemiologic evidence is limited. We assessed the association between coffee consumption and breast cancer risk among high‐risk women who carry __BRCA__ mutati

BRCA1 and BRCA2 mutations in Russian fam

BRCA1 and BRCA2 mutations in Russian familial breast cancer

✍ Irina V. Tereschenko; Victoria M. Basham; Bruce A.J. Ponder; Paul D.P. Pharoah 📂 Article 📅 2002 🏛 John Wiley and Sons 🌐 English ⚖ 24 KB 👁 2 views

We have screened index cases from 25 Russian breast/ovarian cancer families for germ-line mutations in all coding exons of the BRCA1 and BRCA2 genes, using multiplex heteroduplex analysis. In addition we tested 22 patients with breast cancer diagnosed before age 40 without family history and 6 patie

Tamoxifen and contralateral breast cance

Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers: An update

✍ Jacek Gronwald; Nadine Tung; William D. Foulkes; Kenneth Offit; Ruth Gershoni; M 📂 Article 📅 2006 🏛 John Wiley and Sons 🌐 French ⚖ 77 KB

## Abstract Women with a mutation in __BRCA1__ or __BRCA2__ face a lifetime risk of breast cancer of ∼80%, and following the first diagnosis the10‐year risk of contralateral breast cancer is ∼30%. It has been shown that both tamoxifen and oophorectomy prevent contralateral breast cancer, but it is

Effect of pregnancy as a risk factor for

Effect of pregnancy as a risk factor for breast cancer in BRCA1/BRCA2 mutation carriers

✍ Carey A. Cullinane; Jan Lubinski; Susan L. Neuhausen; Parviz Ghadirian; Henry T. 📂 Article 📅 2005 🏛 John Wiley and Sons 🌐 French ⚖ 69 KB 👁 1 views

## Abstract Early age at first birth and multiparity have been associated with a decrease in the risk of breast cancer in women in the general population. We examined whether this relationship is also present in women at high risk of breast cancer due to the presence of a mutation in either of the

Association between BRCA1 and BRCA2 muta

Association between BRCA1 and BRCA2 mutations and cancer phenotype in Spanish breast/ovarian cancer families: Implications for genetic testing

✍ Miguel de la Hoya; Ana Osorio; Javier Godino; Sara Sulleiro; Alicia Tosar; Pedro 📂 Article 📅 2001 🏛 John Wiley and Sons 🌐 French ⚖ 86 KB 👁 1 views

## Abstract Index cases from a clinically relevant cohort of 102 Spanish families with at least 3 cases of breast and/or ovarian cancer (at least 1 case diagnosed before age 50) in the same lineage were screened for germline mutations in the entire coding sequence and intron boundaries of the breas