| Summary: | <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>In this study we have studied 26 tagged single nucleotide polymorphisms (tagSNPs) in <it>RMI1</it>, <it>TOP3A</it>, and <it>BLM </it>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).</p> <p>Results</p> <p>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 <it>TOP3A </it>(rs1563634 and rs12945597) and two SNPs in <it>BLM </it>(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 <it>TOP3A </it>and rs2532105 in <it>BLM </it>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 <it>TOP3A</it>, the risk increment was more pronounced for older carriers.</p> <p>Conclusion</p> <p>These results further support a role of low-penetrance genes involved in BLM-associated homologous recombination for cancer risk.</p>
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