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Deborah Thompson

Publications and source records attributed to Deborah Thompson.

At least 19 recordsLinked to original sources
PubMed2006

PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene.

PALB2 interacts with BRCA2, and biallelic mutations in PALB2 (also known as FANCN), similar to biallelic BRCA2 mutations, cause Fanconi anemia. We identified monoallelic truncating PALB2 mutations in 10/923 individuals with familial breast cancer compared with 0/1,084 controls (P = 0.0004) and show that such mutations confer a 2.3-fold higher risk of breast cancer (95% confidence interval (c.i.) = 1.4-3.9, P = 0.0025). The results show that PALB2 is a breast cancer susceptibility gene and further demonstrate the close relationship of the Fanconi anemia-DNA repair pathway and breast cancer predisposition.

Adult↗
PubMed2006

Mutations in the gene encoding the Sigma 2 subunit of the adaptor protein 1 complex, AP1S2, cause X-linked mental retardation.

In a systematic sequencing screen of the coding exons of the X chromosome in 250 families with X-linked mental retardation (XLMR), we identified two nonsense mutations and one consensus splice-site mutation in the AP1S2 gene on Xp22 in three families. Affected individuals in these families showed mild-to-profound mental retardation. Other features included hypotonia early in life and delay in walking. AP1S2 encodes an adaptin protein that constitutes part of the adaptor protein complex found at the cytoplasmic face of coated vesicles located at the Golgi complex. The complex mediates the recruitment of clathrin to the vesicle membrane. Aberrant endocytic processing through disruption of adaptor protein complexes is likely to result from the AP1S2 mutations identified in the three XLMR-affected families, and such defects may plausibly cause abnormal synaptic development and function. AP1S2 is the first reported XLMR gene that encodes a protein directly involved in the assembly of endocytic vesicles.

Adaptor Protein Complex sigma Subunits↗
PubMed2006

Truncating mutations in the Fanconi anemia J gene BRIP1 are low-penetrance breast cancer susceptibility alleles.

We identified constitutional truncating mutations of the BRCA1-interacting helicase BRIP1 in 9/1,212 individuals with breast cancer from BRCA1/BRCA2 mutation-negative families but in only 2/2,081 controls (P = 0.0030), and we estimate that BRIP1 mutations confer a relative risk of breast cancer of 2.0 (95% confidence interval = 1.2-3.2, P = 0.012). Biallelic BRIP1 mutations were recently shown to cause Fanconi anemia complementation group J. Thus, inactivating truncating mutations of BRIP1, similar to those in BRCA2, cause Fanconi anemia in biallelic carriers and confer susceptibility to breast cancer in monoallelic carriers.

Adult↗
PubMed2006

ATM mutations that cause ataxia-telangiectasia are breast cancer susceptibility alleles.

We screened individuals from 443 familial breast cancer pedigrees and 521 controls for ATM sequence variants and identified 12 mutations in affected individuals and two in controls (P = 0.0047). The results demonstrate that ATM mutations that cause ataxia-telangiectasia in biallelic carriers are breast cancer susceptibility alleles in monoallelic carriers, with an estimated relative risk of 2.37 (95% confidence interval (c.i.) = 1.51-3.78, P = 0.0003). There was no evidence that other classes of ATM variant confer a risk of breast cancer.

Alleles↗
PubMed2006

A test of performance of breast MRI interpretation in a multicentre screening study.

OBJECTIVES: The aim of this study was to assess the consistency and performance of radiologists interpreting breast magnetic resonance imaging (MRI) examinations. MATERIALS AND METHODS: Two test sets of eight cases comprising cancers, benign disease, technical problems and parenchymal enhancement were prepared from two manufacturers' equipment (X and Y) and reported by 15 radiologists using the recording form and scoring system of the UK MRI breast screening study [(MAgnetic Resonance Imaging in Breast Screening (MARIBS)]. Variations in assessments of morphology, kinetic scores and diagnosis were measured by assessing intraobserver and interobserver variability and agreement. The sensitivity and specificity of reporting performances was determined using receiver operating characteristic (ROC) curve analysis. RESULTS: Intraobserver variation was seen in 13 (27.7%) of 47 of the radiologists' conclusions (four technical and seven pathological differences). Substantial interobserver variation was observed in the scores recorded for morphology, pattern of enhancement, quantification of enhancement and washout pattern. The overall sensitivity of breast MRI was high [88.6%, 95% confidence interval (CI) 77.4-94.7%], combined with a specificity of 69.2% (95% CI 60.5-76.7%). The sensitivities were similar for the two test sets (P=.3), but the specificity was significantly higher for the Manufacturer X dataset (P<.001). ROC curve analysis gave an area under the curve of 0.85 (95% CI 0.79-0.92) CONCLUSIONS: Substantial variation in all elements of the scoring system and in the overall diagnostic conclusions was observed between radiologists participating in MARIBS. High overall sensitivity was achieved with moderate specificity. Manufacturer-related differences in specificities possibly occurred because the numerical thresholds set for the scoring system were not optimised for both equipment manufacturers. Scoring systems developed on one equipment software may not be transferable to other manufacturers.

Breast Neoplasms↗
PubMed2006

Evaluation of a prospective scoring system designed for a multicenter breast MR imaging screening study.

PURPOSE: To evaluate prospectively the accuracy of a lesion classification system designed for use in a magnetic resonance (MR) imaging high-breast-cancer-risk screening study. MATERIALS AND METHODS: All participating patients provided written informed consent. Ethics committee approval was obtained. The results of 1541 contrast material-enhanced breast MR imaging examinations were analyzed; 1441 screening examinations were performed in 638 women aged 24-51 years at high risk for breast cancer, and 100 examinations were performed in 100 women aged 23-81 years. Lesion analysis was performed in 991 breasts, which were divided into design (491 breasts) and testing (500 breasts) sets. The reference standard was histologic analysis of biopsy samples, fine-needle aspiration cytology, or minimal follow-up of 24 months. The scoring system involved the use of five features: morphology (MOR), pattern of enhancement (POE), percentage of maximal focal enhancement (PMFE), maximal signal intensity-time ratio (MITR), and pattern of contrast material washout (POCW). The system was evaluated by means of (a) assessment of interreader agreement, as expressed in kappa statistics, for 315 breasts in which both readers analyzed the same lesion, (b) assessment of the diagnostic accuracy of the scored components with receiver operating characteristic curve analysis, and (c) logistic regression analysis to determine which components of the scoring system were critical to the final score. A new simplified scoring system developed with the design set was applied to the testing set. RESULTS: There was moderate reader agreement regarding overall lesion outcome (ie, malignant, suspicious, or benign) (kappa=0.58) and less agreement regarding the scored components. The area under the receiver operating characteristic curve (AUC) for the overall lesion score, 0.88, was higher than the AUC for any one component. The components MOR, POE, and POCW yielded the best overall result. PMFE and MITR did not contribute to diagnostic utility. Applying a simplified scoring system to the testing set yielded a nonsignificantly (P=.2) higher AUC than did applying the original scoring system (sensitivity, 84%; specificity, 86.0%). CONCLUSION: Good diagnostic accuracy can be achieved by using simple qualitative descriptors of lesion enhancement, including POCW. In the context of screening, quantitative enhancement parameters appear to be less useful for lesion characterization.

Adult↗
PubMed2006

Association of the progesterone receptor gene with breast cancer risk: a single-nucleotide polymorphism tagging approach.

Association studies on susceptibility to breast cancer using single nucleotide polymorphisms (SNP) in the progesterone receptor (PGR) gene have been previously published, but the results have been inconclusive. We used a comprehensive SNP-tagging approach to search for low-penetrance susceptibility alleles in a study of up to 4,647 cases and 4,564 controls, in a two-stage study design. We identified seven tagging SNPs using genotype data from the National Institute of Environmental Health Sciences (NIEHS) Environmental Genome Project and typed these, and an additional three SNPs, in 2,345 breast cancer cases and 2,284 controls (set 1). Three SNPs showed no evidence for association and were not studied further, whereas seven SNPs (rs11571171, rs7116336, rs660149, rs10895068, rs500760, rs566351, and rs1042838) exhibited significant associations at P < 0.1 using either a heterogeneity or trend test and progressed to be genotyped in set 2. After both stages, only one SNP was significantly associated with an increased risk of breast cancer - the PGR-12 (rs1042638) V660L valine to leucine polymorphism [VL heterozygotes (odds ratio, 1.13; 95% confidence interval, 1.03-1.24) and the LL homozygotes (odds ratio, 1.30; 95% confidence interval, 0.98-1.73), P(het) = 0.008, P(trend) = 0.002]. Similar estimates were obtained in a combined analysis of our data with those from three other published studies. We conclude that the 660L allele may be associated with a moderately increased risk of breast cancer, but that other common SNPs in the PGR gene are unlikely to be associated with a substantial risk of breast cancer.

Aged↗
PubMed2006

A multicenter study of cancer incidence in CHEK2 1100delC mutation carriers.

The CHEK2 1100delC protein-truncating mutation has a carrier frequency of approximately 0.7% in Northern and Western European populations and confers an approximately 2-fold increased risk of breast cancer. It has also been suggested to increase risks of colorectal and prostate cancer, but its involvement with these or other types of cancer has not been confirmed. The incidence of cancer other than breast cancer in 11,116 individuals from 734 non-BRCA1/2 breast cancer families from the United Kingdom, Germany, Netherlands, and the United States was compared with that predicted by population rates. Relative risks (RR) to carriers and noncarriers were estimated by maximum likelihood, via the expectation-maximization algorithm to allow for unknown genotypes. Sixty-seven families contained at least one tested CHEK2 1100delC mutation carrier. There was evidence of underreporting of cancers in male relatives (422 cancers observed, 860 expected) but not in females (322 observed, 335 expected); hence, we focused on cancer risks in female carriers. The risk of cancers other than breast cancer in female carriers was not significantly elevated, although a modest increase in risk could not be excluded (RR, 1.18; 95% confidence interval, 0.64-2.17). The carrier risk was not significantly raised for any individual cancer site, including colorectal cancer (RR, 1.60; 95% confidence interval, 0.54-4.71). However, between ages 20 to 50 years, the risks of colorectal and lung cancer were both higher in female carriers than noncarriers (P = 0.041 and 0.0001, respectively). There was no evidence of a higher prostate cancer risk in carriers than noncarriers (P = 0.26), although underreporting of male cancers limited our power to detect such a difference. Our results suggest that the risk of cancer associated with CHEK2 1100delC mutations is restricted to breast cancer, although we cannot rule out a small increase in overall cancer risk.

Breast Neoplasms↗
PubMed2005

IGF1 and IGFBP3 tagging polymorphisms are associated with circulating levels of IGF1, IGFBP3 and risk of breast cancer.

Experimental and observational studies in humans and animals suggest that insulin-like growth factor 1 (IGF1) and its principal binding protein, IGFBP3, may influence breast cancer susceptibility. We have examined the association of nine and four single nucleotide polymorphisms (SNPs) in the IGF1 gene and in the IGFBP3 genes, respectively, with circulating levels of their gene products in a population-based study of 600 middle-aged men and women, and in a breast cancer case-control study, comprised 4647 cases and 4564 controls. All study participants are from the East Anglian region of UK. SNPs were specifically chosen to tag all other known SNPs in each gene. Several SNPs in each gene are associated both with circulating levels of their respective proteins and with risk of breast cancer. In particular, the c allele of IGF1 SNPrs1520220 is associated with increased circulating IGF1 (r2=2.1%, P-trend=0.003) in females and an increased risk of breast cancer: odds ratio (OR) (cc/gg)=1.41; 95% confidence intervals (95% CI) 1.11-1.79, P-trend=0.03. The a allele of IGFBP3 SNP rs2854744 is associated with increased circulating IGFBP3 (r2=9.7%, P<10(-9)) and a decreased risk of breast cancer: OR (aa/cc)=0.87; 95% CI 0.77-0.99, P=0.03. Our data indicate that common variants in the IGF1 and IGFBP3 genes are associated with differences in circulating levels of IGF1 and IGFBP3 and with breast cancer risk. More specifically and consistent with experimental models, our data suggest that higher IGF1 levels may increase the risk of breast cancer but higher IGFBP3 levels may be protective.

Breast Neoplasms↗
PubMed2005

Cancer risks and mortality in heterozygous ATM mutation carriers.

BACKGROUND: Homozygous or compound heterozygous mutations in the ATM gene are the principal cause of ataxia telangiectasia (A-T). Several studies have suggested that heterozygous carriers of ATM mutations are at increased risk of breast cancer and perhaps of other cancers, but the precise risk is uncertain. METHODS: Cancer incidence and mortality information for 1160 relatives of 169 UK A-T patients (including 247 obligate carriers) was obtained through the National Health Service Central Registry. Relative risks (RRs) of cancer in carriers, allowing for genotype uncertainty, were estimated with a maximum-likelihood approach that used the EM algorithm. Maximum-likelihood estimates of cancer risks associated with three groups of mutations were calculated using the pedigree analysis program MENDEL. All statistical tests were two-sided. RESULTS: The overall relative risk of breast cancer in carriers was 2.23 (95% confidence interval [CI] = 1.16 to 4.28) compared with the general population but was 4.94 (95% CI = 1.90 to 12.9) in those younger than age 50 years. The relative risk for all cancers other than breast cancer was 2.05 (95% CI = 1.09 to 3.84) in female carriers and 1.23 (95% CI = 0.76 to 2.00) in male carriers. Breast cancer was the only site for which a clear risk increase was seen, although there was some evidence of excess risks of colorectal cancer (RR = 2.54, 95% CI = 1.06 to 6.09) and stomach cancer (RR = 3.39, 95% CI = 0.86 to 13.4). Carriers of mutations predicted to encode a full-length ATM protein had cancer risks similar to those of people carrying truncating mutations. CONCLUSION: These results confirm a moderate risk of breast cancer in A-T heterozygotes and give some evidence of an excess risk of other cancers but provide no support for large mutation-specific differences in risk.

Adult↗
PubMed2005

Occupational exposure to metalworking fluids and risk of breast cancer among female autoworkers.

BACKGROUND: Metalworking fluids (MWF) are used for lubrication during metal manufacturing. Previous studies have observed increased risks of several cancers among MWF-exposed workers. We hypothesized that MWF may be associated with risk of breast cancer because they can contain carcinogenic or endocrine-disrupting chemicals. METHODS: We conducted a case-control study nested in a cohort of 4,680 female automobile workers employed for at least 3 years between 1/1/41 and 1/1/85, with follow-up through 1994. Cases were identified using the National Death Index (NDI), Michigan cancer registries, and company records. Detailed quantitative MWF exposure data were available for each subject, although data on known breast cancer risk factors were not. RESULTS: Ninety-nine cases of breast cancer and 626 matched controls were identified. There was a weak positive association between lifetime cumulative exposure to soluble MWF and breast cancer risk, but no evidence of association with either straight or synthetic fluids. When exposure was divided into time-windows, the association was strongest for soluble MWF in the decade preceding diagnosis. Controlling for earlier exposures, there was an odds ratio of 1.18 (95% CI=1.02-1.35) per mg/m3-year of cumulative exposure to soluble MWF in this 10-year period. CONCLUSION: This hypothesis-generating study provides some preliminary evidence for an association between exposure to soluble MWF and increased risk of breast cancer. Additional studies of MWF and breast cancer, with data on known breast cancer risk factors, are warranted.

Adult↗
PubMed2005

Two ATM variants and breast cancer risk.

The ATM gene is mutated in ataxia-telangiectasia (AT). Heterozygote female relatives of AT cases have a 2-7fold increased risk of breast cancer. We previously reported high risks of breast cancer associated with certain ATM variants. To estimate the risks more precisely, we have examined two ATM variants, c.1066-6T>G (IVS10-6T>G) and c.4258C>T (p.Leu1420Phe), in additional cases and controls from the same Australian cohorts previously used to estimate the risk of breast cancer associated with c.1066-6T>G. A total of 775 and 84 population-based controls were genotyped for the c.1066-6T>G and c.4258C>T ATM variants respectively, as were index cases from 378 and 373 non-BRCA1/2 breast cancer families. Penetrance was estimated by Bayes factor analysis. The allele frequencies of ATM c.1066-6T>G and c.4258C>T estimated from controls were 0.005 (95% CI=0.002 to 0.009) and 0.012 (95% CI=0.001 to 0.042), respectively. We identified three new breast cancer families with c.1066-6T>G, and seven families with c.4258C>T. Combining with the two c.1066-6T>G families previously reported, the estimated penetrance to age 70 of c.1066-6T>G was 17.2% (95% CI=4.7% to 37.5%). For c.4258C>T, the estimated average penetrance was 4.8% (95% CI 1.7% to 10.1%). In conclusion, we found no evidence that the ATM c.4258C>T variant increases breast cancer risk, and little evidence that c.1066-6T>G confers an elevated risk. Analysis of additional families will be necessary to define more precisely the risk, if any, associated with c.1066-6T>G.

Ataxia Telangiectasia Mutated Proteins↗
PubMed2005

Reading protocol for dynamic contrast-enhanced MR images of the breast: sensitivity and specificity analysis.

PURPOSE: To prospectively determine sensitivity and specificity of breast magnetic resonance (MR) imaging in a screening and symptomatic population by using independent double reading, with histologic or cytologic results or a minimum 18-month follow-up as the standard. MATERIALS AND METHODS: Informed consent and ethical approval were obtained. Reader performance was analyzed in 44 radiologists at 18 centers from 1541 examinations, including 1441 screening examinations in 638 high-risk women aged 24-51 years (mean, 40.5 years) and 100 examinations in symptomatic women aged 23-81 years (mean, 49.2 years). A screening protocol of dynamic T1-weighted three-dimensional imaging and 0.2 mmol/kg gadolinium-based intravenous contrast agent was used. Logistic and Poisson regressions were used to analyze reader performance in relation to experience. Correlation between readers was determined with kappa statistics. Sensitivity and specificity were analyzed according to reader, field strength, machine type, and histologic results. RESULTS: The proportion of studies with lesions analyzed reduced significantly with reader experience (odds ratio, 0.84 per 6 months; P < .001), and number of regions per lesion analyzed also diminished (incidence rate ratio, 0.98 per 6 months; P = .047). The two readers for each study agreed 87% of the time, with a moderately good kappa statistic of 0.52 (95% confidence interval [CI]: 0.45, 0.58). By taking the reading with the highest score (most likely to be malignant) from each double-read study, sensitivity was 91% (95% CI: 83%, 96%) and specificity was 81% (95% CI: 79%, 83%). Single readings had 7% lower sensitivity (95% CI: 4%, 11%) and 7% higher specificity (95% CI: 6%, 7%). Sensitivity did not differ between MR imager manufacturers or between 1.0- and 1.5-T field strength, but there were significant differences in specificity for machine type (P = .001) and for field strength adjusted for manufacturer (P = .001). Specificity, but not sensitivity, was higher in women younger than 50 years (P = .02). CONCLUSION: Independent double reading by 44 radiologists blinded to mammography results showed sensitivity and specificity acceptable for screening; sensitivity was higher when two readings were used, at the cost of specificity. Interreader correlation was moderately good, and evidence of learning was seen. Equipment manufacturer, field strength, and age affected specificity but not sensitivity.

Adult↗
PubMed2005

Exploratory study of ovarian intraepithelial neoplasia.

PURPOSE: This was an exploratory study to test two hypotheses related to potential epithelial precursors to ovarian cancer: (a) histologically normal ovarian surface epithelium exhibited changes in the nuclear chromatin pattern, which indicate an ovarian abnormality, and (b) such changes were detectable in the ovarian surface epithelium of cancer-free subjects who were at high risk for ovarian cancer. EXPERIMENTAL DESIGN: Ovaries were carefully collected to avoid damage to the surface epithelium. Five-micron-thick histologic sections were cut and stained with H&E. High-resolution images were recorded from the ovarian surface epithelium and from the underlying stroma of ovaries from normal women (10 cases), women at high risk of developing ovarian cancer (7 cases), and histologically normal areas adjacent to ovarian cancer (3 cases). Karyometric features and measurements of nuclear abnormality were computed for 3,390 epithelial nuclei. Discriminant function analyses and unsupervised learning algorithms were employed to define deviations from normal and to identify the subpopulations of nuclei exhibiting these changes. RESULTS: Epithelium from ovaries harboring a malignant lesion had changes in the nuclear chromatin pattern consistent with a second phenotype, which were not visually detected with histopathologic surveillance. This phenotype was also present in the ovaries obtained from women at increased risk of ovarian cancer, suggesting that it may represent a premalignant abnormality. These changes were statistically significant. CONCLUSION: The observed changes in karyometric features were sufficiently distinct to warrant further study as both diagnostic and prognostic biomarkers for early detection and prevention of ovarian cancer.

Carcinoma in Situ↗
PubMed2004

Acetyl-CoA carboxylase alpha gene and breast cancer susceptibility.

The identification of an interaction between BRCA1 and acetyl-CoA carboxylase alpha (ACCalpha), a key enzyme in lipid synthesis, led us to investigate the role of ACCalpha in breast cancer development, where it might contribute to the energy-sensing mechanisms of malignant transformation. In order to investigate if certain ACCalpha alleles may be high-risk breast cancer susceptibility alleles, 37 extended breast and breast/ovarian cancer families negative for BRCA1 and BRCA2 mutations were exhaustively screened for sequence variations in the entire coding sequence, intron-exon junctions, 5'UTR, 3'UTR (untranslated regions) and the promoter regions of the ACCalpha gene. Two possibly disease-associated ACCalpha variants were each identified in a single family and were not present in 137 controls. Multiple polymorphisms were detected in breast cancer families, including 12 single nucleotide polymorphisms where the frequency of the rare allele estimated in controls was >0.10. The observed lack of variation in the ACCalpha coding region along with the presence of extended areas of linkage disequilibrium and low haplotype diversity indicates an overall high preservation of this gene. The prevalence of the ACCalpha haplotypes composed of common polymorphisms was determined in 453 breast cancer cases and 469 female controls. One haplotype was found to be associated with a substantial and highly significant increase in breast cancer risk (odds ratio = 3.10, 95% confidence interval 1.87-5.14, P < 0.0001), whereas three other haplotypes were found to have a protective effect. Our results indicate that mutations in the ACCalpha gene are unlikely to be a major cause of high-risk breast cancer susceptibility; however, certain common ACCalpha alleles may influence breast cancer risk. This study provides the first insight into the involvement of the ACCalpha gene in breast cancer predisposition and calls for further, large-scale studies that will be needed to understand the role of ACCalpha in tumour susceptibility and development.

Acetyl-CoA Carboxylase↗
PubMed2004

Safety and efficacy of dose-intensive oral vitamin A in subjects with sun-damaged skin.

PURPOSE: Previously, we reported the results of a Phase III, placebo-controlled trial in 2297 randomized participants with moderately severe actinic keratoses wherein 25000 IU/day vitamin A caused a 32% risk reduction in squamous cell skin cancers. We hypothesized that dose escalation of vitamin A to 50000 or 75000 IU/day would be both safe and more efficacious in skin cancer chemoprevention. EXPERIMENTAL DESIGN: One hundred and twenty-nine participants with severely sun-damaged skin on their lateral forearms were randomized to receive placebo or 25000, 50000, or 75000 IU/day vitamin A for 12 months. The primary study end points were the clinical and laboratory safety of vitamin A, and the secondary end points included quantitative, karyometric image analysis and assessment of retinoid and rexinoid receptors in sun-damaged skin. RESULTS: There were no significant differences in expected clinical and laboratory toxicities between the groups of participants randomized to placebo, 25000 IU/day, 50000 IU/day, and 75000 IU/day. Karyometric features were computed from the basal cell layer of skin biopsies, and a total of 22600 nuclei from 113 participants were examined, showing statistically significant, dose-response effects for vitamin A at the 25000 and 50000 IU/day doses. These karyometric changes correlated with increases in retinoic acid receptor alpha, retinoic acid receptor beta, and retinoid X receptor alpha at the 50000 IU/day vitamin A dose. CONCLUSIONS: The vitamin A doses of 50000 and 75000 IU/day for 1 year proved safe and equally more efficacious than the 25000 IU/day dose and can be recommended for future skin cancer chemoprevention studies.

Administration, Oral↗
PubMed2004

Are ATM mutations 7271T-->G and IVS10-6T-->G really high-risk breast cancer-susceptibility alleles?

Two mutations of the ATM gene were recently suggested to confer breast cancer risks similar to mutations of BRCA1 or BRCA2. Here, we set out to confirm these findings in 961 families with non-BRCA1/BRCA2 breast cancer from diverse geographical regions. We did not detect the ATM 7271T-->G mutation in any family. The ATM IVS10-6T-->G mutation was detected in eight families, which was similar to its frequency among population-matched control individuals (pooled Mantel-Haenszel odds ratio = 1.60; 95% confidence interval = 0.48 to 5.35; P = 0.44). Bayesian analysis of linkage in the ATM IVS10-6T-->G-positive families showed an overall posterior probability of causality for this mutation of 0.008. We conclude that the ATM IVS10-6T-->G mutation does not confer a significantly elevated breast cancer risk and that ATM 7271T-->G is a rare event in familial breast cancer.

Alleles↗