Genetic variant of the human homologous recombination-associated gene RMI1 (S455N) impacts the risk of AML/MDS and malignant melanoma.

Summary, in English

The newly identified protein BLAP75/RMI1 associates with the helicase BLM and is critical for the function of the homologous recombination complex. Mutations altering BLM function are associated with highly elevated cancer susceptibility (Bloom's syndrome). We have analyzed the common polymorphism Ser455Asn in RMI1 and its association with cancer risk in acute myeloid leukemia (AML, N=93), myelodysplatic syndromes (MDS, N=74), and malignant melanoma (MM, N=166). Two control groups were used: one population-based (N=119) and one recruited from spouses of cancer patients (N=189). The results showed a consistent pattern, where carriers of the Asn variant had a significantly increased risk of AML/MDS. The risk of AML/MDS for SerAsn+AsnAsn subjects was odds ratio (OR)=1.7, 95% confidence interval (CI) 1.1-2.5 or MM was OR=1.5, 95% CI 1.0-2.2. Age might modify the effect of RMI1 on cancer risk. This was most evident for MM: AsnAsn homozygotes > or =64 years showed OR=2.7, 95% CI 1.1-6.0, whereas individuals <64 years showed OR=0.87, 95% CI 0.31-2.5. These results indicate a role of low-penetrance genes involved in BLM-associated homologous recombination for cancer risk.

• Author: Karin Broberg Palmgren; Mattias Höglund; Cecilia Gustafsson; Jonas Björk; Christian Ingvar; Maria Albin; Håkan Olsson
• Department/s: Division of Occupational and Environmental Medicine, Lund University; Division of Clinical Genetics; Geriatric Medicine; Surgery (Lund); Breastcancer-genetics; Medical oncology; Tumor microenvironment
• Publishing year: 2007
• Language: English
• Pages: 38-44
• Publication/Series: Cancer Letters
• Volume: 258
• Issue: 1
• Links: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17900800&dopt=Abstract; http://dx.doi.org/10.1016/j.canlet.2007.08.005
• Document type: Journal article
• Publisher: Elsevier
• Topic: Cancer and Oncology
• Keywords: Acute/genetics* *Male *Melanoma/genetics* *Middle Aged *Myelodysplastic Syndromes/genetics* *Nuclear Proteins/genetics* *Polymerase Chain Reaction *Polymorphism; Genetic *RecQ Helicases *Recombination; Myeloid; *Adenosine Triphosphatases/genetics *Adult *Aged *Aged; 80 and over *Bloom Syndrome/genetics *Carrier Proteins/genetics* *Case-Control Studies *DNA Helicases/genetics *Female *Genetic Variation* *Genotype *Humans *Leukemia; Genetic* *Skin Neoplasms/genetics*
• Status: Published
• Research group: Geriatric Medicine
• ISBN/ISSN/Other: ISSN: 1872-7980