Single-nucleotide polymorphisms in the RB1 gene and association with breast cancer in the British population
| Autor: | Clare Jordan, Robert Luben, Craig Luccarini, Doug Easton, Alison M. Dunning, B. A. J. Ponder, Paul D.P. Pharoah, Shahana Ahmed, Fabienne Lesueur, Honglin Song |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Cancer Research
Linkage disequilibrium Breast Neoplasms Single-nucleotide polymorphism Biology Polymerase Chain Reaction Polymorphism Single Nucleotide Retinoblastoma Protein Linkage Disequilibrium breast cancer Breast cancer Gene Frequency Risk Factors single-nucleotide polymorphisms medicine Humans Genetic Predisposition to Disease Allele frequency Aged Genetics Haplotype Genetics and Genomics Middle Aged medicine.disease Penetrance United Kingdom Genotype frequency Minor allele frequency Haplotypes Oncology Case-Control Studies Female RB1 |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1038/sj.bjc.6603160 |
| Popis: | A substantial proportion of the familial risk of breast cancer may be attributable to genetic variants each contributing a small effect. pRb controls the cell cycle and polymorphisms within it are candidates for such low penetrance susceptibility alleles, since the gene has been implicated in several human tumours, particularly breast cancer. The purpose of this study was to determine whether common variants in the RB1 gene are associated with breast cancer risk. We assessed 15 tagging single-nucleotide polymorphisms (SNPs) using a case-control study design (nor = 4474 cases and nor = 4560 controls). A difference in genotype frequencies was found between cases and controls for rs2854344 in intron 17 (P-trend = 0.007) and rs198580 in intron 19 (P-trend = 0.018). Carrying the minor allele of these SNPs appears to confer a protective effect on breast cancer risk (odd ratio (OR) = 0.86 (0.76-0.96) for rs2854344 and OR = 0.80 (0.66-0.96) for rs198580). However, after adjusting for multiple testing these associations were borderline with an adjusted P-trend = 0.068 for the most significant SNP (rs2854344). The RB1 gene is not known to contain any coding SNPs with allele frequenciesor = 5% but several intronic variants are in perfect linkage disequilibrium with the associated SNPs. Replication studies are needed to confirm the associations with breast cancer. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|