The BRCA1 Ashkenazi founder mutations occur on common haplotypes and are not highly correlated with anonymous single nucleotide polymorphisms likely to be used in genome-wide case-control association studies

BackgroundWe studied linkage disequilibrium (LD) patterns at the BRCA1 locus, a susceptibility gene for breast and ovarian cancer, using a dense set of 114 single nucleotide polymorphisms in 5 population groups. We focused on Ashkenazi Jews in whom there are known founder mutations, to address the question of whether we would have been able to identify the 185delAG mutation in a case-control association study (should one have been done) using anonymous genetic markers. This mutation is present in approximately 1% of the general Ashkenazi population and 4% of Ashkenazi breast cancer cases. We evaluated LD using pairwise and haplotype-based methods, and assessed correlation of SNPs with the founder mutations using Pearson's correlation coefficient.ResultsBRCA1 is characterized by very high linkage disequilibrium in all populations spanning several hundred kilobases. Overall, haplotype blocks and pair-wise LD bins were highly correlated, with lower LD in African versus non-African populations. The 185delAG and 5382insC founder mutations occur on the two most common haplotypes among Ashkenazim. Because these mutations are rare, even though they are in strong LD with many other SNPs in the region as measured by D-prime, there were no strong associations when assessed by Pearson's correlation coefficient, r (maximum of 0.04 for the 185delAG).ConclusionSince the required sample size is related to the inverse of r, this suggests that it would have been difficult to map BRCA1 in an Ashkenazi case-unrelated control association study using anonymous markers that were linked to the founder mutations

Risk Stratification System for Oral Cancer Screening

Oral cavity and oropharyngeal cancer (oral cancer) is a deadly disease that is increasing in incidence. World-wide 5-year survival is only 50% due to delayed intervention with more than half of diagnoses at stage III and IV, whereas earlier detection (stage I and II) yields survival rates up to 80%–90%. Salivary soluble CD44 (CD44), a tumor-initiating marker, and total protein levels may facilitate oral cancer risk assessment and early intervention. This study used a hospital-based design with 150 cases and 150 frequency-matched controls to determine whether CD44 and total protein levels in oral rinses were associated with oral cancer independent of age, gender, race, ethnicity, tobacco and alcohol use, and socioeconomic status (SES). High-risk subjects receiving oral cancer prevention interventions as part of a community- based program (n=150) were followed over 1 year to determine marker specificity and variation. CD44 ≥5.33 ng/ml was highly associated with case status (adjusted OR 14.489, 95%CI: 5.973, 35.145; p<.0001, versus reference group CD44 <2.22 ng/ml and protein <1.23 mg/ml). Total protein aided prediction above CD44 alone. Sensitivity and specificity in the frequency-matched study was 80% and 48.7%, respectively. However, controls were not representative of the target screening population due, in part, to a high rate of prior cancer. In contrast, specificity in the high-risk community was 74% and reached 95% after annual retesting. Simple and inexpensive salivary CD44 and total protein measurements may help identify individuals at heightened risk for oral cancer from the millions who partake in risky behaviors

The Ashkenazi founder mutations occur on common haplotypes and are not highly correlated with anonymous single nucleotide polymorphisms likely to be used in genome-wide case-control association studies-1

<p><b>Copyright information:</b></p><p>Taken from "The Ashkenazi founder mutations occur on common haplotypes and are not highly correlated with anonymous single nucleotide polymorphisms likely to be used in genome-wide case-control association studies"</p><p>http://www.biomedcentral.com/1471-2156/8/68</p><p>BMC Genetics 2007;8():68-68.</p><p>Published online 4 Oct 2007</p><p>PMCID:PMC2093936.</p><p></p>wn true size. Anchor lines link to position of the SNP within the region. B-F) LDSelect creates bins of SNPs that have an value of 0.8 or greater with at least one other SNP in the bin. Each vertical line and arrowhead represents a SNP, with dashed lines and shaded background connecting SNPs within the same bin. Down arrowheads indicate Tag SNPs (those with ≥ 0.8 with all other SNPs in a bin). Note that this use of the term Tag-SNP is different from Haploview – with LDSelect, only one Tag-SNP per bin would be required to capture the majority of the nucleotide diversity. Singleton bins (SNPs that did not have ≥ 0.8 with any other SNP) are indicated by solid dots on a single row. SNP number refers to numbering in column 1 of Table 1

The Ashkenazi founder mutations occur on common haplotypes and are not highly correlated with anonymous single nucleotide polymorphisms likely to be used in genome-wide case-control association studies-0

<p><b>Copyright information:</b></p><p>Taken from "The Ashkenazi founder mutations occur on common haplotypes and are not highly correlated with anonymous single nucleotide polymorphisms likely to be used in genome-wide case-control association studies"</p><p>http://www.biomedcentral.com/1471-2156/8/68</p><p>BMC Genetics 2007;8():68-68.</p><p>Published online 4 Oct 2007</p><p>PMCID:PMC2093936.</p><p></p>e indicated by arrowheads; htSNPs in only one population are shown on a yellow background while the single htSNP shared between all populations is shown on a green background