| 1. |
- Broberg Palmgren, Karin, et al.
(författare)
-
Association between polymorphisms in RMI1, TOP3A, and BLM and risk of cancer, a case-control study.
- 2009
-
Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 9:May 11
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Mutations altering BLM function are associated with highly elevated cancer susceptibility (Bloom syndrome). Thus, genetic variants of BLM and proteins that form complexes with BLM, such as TOP3A and RMI1, might affect cancer risk as well. METHODS: In this study we have studied 26 tagged single nucleotide polymorphisms (tagSNPs) in RMI1, TOP3A, and BLM and their associations with cancer risk in acute myeloid leukemia/myelodysplatic syndromes (AML/MDS; N = 152), malignant melanoma (N = 170), and bladder cancer (N = 61). Two population-based control groups were used (N = 119 and N = 156). RESULTS: Based on consistency in effect estimates for the three cancer forms and similar allelic frequencies of the variant alleles in the control groups, two SNPs in TOP3A (rs1563634 and rs12945597) and two SNPs in BLM (rs401549 and rs2532105) were selected for analysis in breast cancer cases (N = 200) and a control group recruited from spouses of cancer patients (N = 131). The rs12945597 in TOP3A and rs2532105 in BLM showed increased risk for breast cancer. We then combined all cases (N = 584) and controls (N = 406) respectively and found significantly increased risk for variant carriers of rs1563634 A/G (AG carriers OR = 1.7 [95%CI 1.1-2.6], AA carriers OR = 1.8 [1.2-2.8]), rs12945597 G/A (GA carriers OR = 1.5 [1.1-1.9], AA carriers OR = 1.6 [1.0-2.5]), and rs2532105 C/T (CT+TT carriers OR = 1.8 [1.4-2.5]). Gene-gene interaction analysis suggested an additive effect of carrying more than one risk allele. For the variants of TOP3A, the risk increment was more pronounced for older carriers. CONCLUSION: These results further support a role of low-penetrance genes involved in BLM-associated homologous recombination for cancer risk.
|
|
| 2. |
|
|
| 3. |
- Broberg Palmgren, Karin, et al.
(författare)
-
Genetic variant of the human homologous recombination-associated gene RMI1 (S455N) impacts the risk of AML/MDS and malignant melanoma.
- 2007
-
Ingår i: Cancer Letters. - : Elsevier BV. - 1872-7980 .- 0304-3835. ; 258:1, s. 38-44
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
