NBS1 variant I171V and breast cancer risk

Abstract

The NBS1/p95 protein has a pivotal role in the sensing and repair of chromosome breaks. A missense mutation in the NBS1 gene, I171V, has recently been associated with a ninefold increased risk of breast cancer in Polish patients. Positive associations have also been reported for leukaemia and larynx cancer suggesting that I171V could be a more general susceptibility factor for malignancies. We investigated the prevalence of this mutation in two large hospital-based case-control series from Germany and from the Republic of Belarus. The I171V substitution was detected in 20/1,636 Byelorussian breast cancer patients and in 18/1,014 Byelorussian controls (OR: 0.68; 95%CI: 0.36-1.30, P=0.3). The I171V substitution was furthermore detected in 10/1,048 German breast cancer patients and in 7/1,017 German controls (OR: 1.39; 95%CI: 0.53-3.67, P=0.7). There were no significant differences between I171V carriers and non-carriers among the cases with regard to age at diagnosis, family history or bilateral occurrence of disease. A meta-analysis of all hitherto available studies did not reveal a difference in the prevalence of I171V between breast cancer cases and controls (OR: 1.05; 95%CI: 0.64-1.74, P=0.9). We conclude that the I171V substitution is unlikely to constitute a strong risk factor for breast cancer in our study populations.

Mitochondrial NADH-dehydrogenase subunit 3 (ND3) polymorphism (A10398G) and sporadic breast cancer in Poland

“…Genes correlated with breast cancer susceptibility include also the ''guardian of the genome'' TP53, and genes of proteins from p53-DNA repair-pathways-the PTEN (phosphatase and tensin homolog, also called mutated in multiple advanced cancers 1) gene, and the CHEK2 (protein kinase CHK2 isoform c) gene. Recent studies have revealed new breast cancer markers like NBS1/p95 [29] and PALB2. PALB2 protein interacts with BRCA2, and is involved in homologous recombination and the repair of DNA double-strand breaks [30,31].…”

Some common mutations of RAD50 and NBS1 in western populations do not contribute significantly to Chinese non-BRCA1/2 hereditary breast cancer

“…A total of 192 women with no personal or family history of cancer were enrolled as normal control from Cancer Hospital of Fudan University between 2003 and 2007. This project has been approved by the Scientific and Ethical Committee of the Cancer Hospital of Fudan University.Oligonucleotide primers and polymerase chain reaction (PCR) conditions as former publications were used to amplify the specific segments which spanned the three mutation spots (RAD50 687delT, NBS1 657del5 and NBS1 I171 V) [3,5,6]. The PCR and DNA sequencing analysis were performed as described previously [4].…”

A Rare Polymorphic Variant of NBS1 Reduces DNA Repair Activity and Elevates Chromosomal Instability

“…However, other groups did not find a similar association in European patients with breast cancer, leukemia, or lymphoma (29)(30)(31). It remains unclear whether this particular polymorphic variant of the NBS1 gene is associated with cancer.…”