Biomedical subjects

Andreas Braun

Publications and source records attributed to Andreas Braun.

At least 19 recordsLinked to original sources

PubMed2006

Evaluation of selective calculus removal by a fluorescence feedback-controlled Er:YAG laser in vitro.

OBJECTIVES: To evaluate the removal of subgingival calculus and dental hard tissues depending on the threshold level of a fluorescence feedback-controlled Er:YAG laser. MATERIAL AND METHODS: Twenty teeth with calculus on the root surface were treated with an Er:YAG laser. Laser settings were 140 mJ and 10 Hz. The initial fluorescence threshold level of 5 [U] was reduced at intervals of 1 [U] for every laser treatment. Areas of residual calculus (RC) were evaluated using a surface analysis software. Loss of dental hard tissues was assessed by histomorphometric analysis of undecalcified ground sections. RESULTS: Using a threshold value of 5 [U], the median amount of RC was 11% (0-78%). By lowering the threshold levels, the amount of RC decreased [level 1 [U]: 0% (0-26%)]. The laser-treated root surfaces revealed a statistically significant reduction of the cementum thickness [median: 80 microm (0-250)] compared with the non-treated opposite side [median: 90 microm (30-250)] (p<0.05). CONCLUSION: The amount of RC following laser irradiation depends on the fluorescence threshold level for a feedback-controlled Er:YAG laser. It might be suggested that this laser system may be used with a threshold level even lower than 5 [U] without removing a clinically relevant amount of root cementum.

Aluminum Silicates↗

PubMed2006

Using DNA pools for genotyping trios.

The genotyping of mother-father-child trios is a very useful tool in disease association studies, as trios eliminate population stratification effects and increase the accuracy of haplotype inference. Unfortunately, the use of trios for association studies may reduce power, since it requires the genotyping of three individuals where only four independent haplotypes are involved. We describe here a method for genotyping a trio using two DNA pools, thus reducing the cost of genotyping trios to that of genotyping two individuals. Furthermore, we present extensions to the method that exploit the linkage disequilibrium structure to compensate for missing data and genotyping errors. We evaluated our method on trios from CEPH pedigree 66 of the Coriell Institute. We demonstrate that the error rates in the genotype calls of the proposed protocol are comparable to those of standard genotyping techniques, although the cost is reduced considerably. The approach described is generic and it can be applied to any genotyping platform that achieves a reasonable precision of allele frequency estimates from pools of two individuals. Using this approach, future trio-based association studies may be able to increase the sample size by 50% for the same cost and thereby increase the power to detect associations.

Adult↗

PubMed2006

Association of the PDCD5 locus with lung cancer risk and prognosis in smokers.

PURPOSE: Whole-genome scan association analysis was carried out to identify genetic variants predictive of lung cancer risk in smokers and to confirm the identified variants in an independent sample. PATIENTS AND METHODS: A case-control study was performed using two pools consisting of DNA from 322 German smoking lung cancer patients and 273 healthy smoking controls, respectively. A replication study was carried out using 254 Italian lung adenocarcinoma (ADCA) patients and 235 healthy controls. RESULTS: Patients with genotypes GG or CG for the rs1862214 single nucleotide polymorphism, 5' upstream of the programmed cell death 5 (PDCD5) gene, compared with those with the common genotype CC showed an increased risk of lung cancer (odds ratio, 1.6; 95% CI, 1.2 to 2.1) and a higher incidence of poor clinical stage disease (hazard ratio [HR], 1.9; 95% CI, 1.1 to 3.4; P = .023), nodal involvement (HR, 1.9; 95% CI, 1.1 to 3.6; P = .033), and short-term survivorship (HR, 1.8; 95% CI, 1.2 to 2.6, P = .003). PDCD5 mRNA expression levels were approximately 2.4-fold lower in lung ADCA as compared to normal lung tissue. Human NCI-H520 cancer cells transfected with PDCD5 cDNA showed decreased colony-forming ability. CONCLUSION: These results suggest that the rs1862214 polymorphism in PDCD5 is predictive for lung cancer risk and prognosis, and that PDCD5 may represent a novel tumor suppressor gene influencing lung cancer.

Adenocarcinoma↗

PubMed2006

Spectrophotometric and visual evaluation of vital tooth bleaching employing different carbamide peroxide concentrations.

OBJECTIVE: The aim of the present study was to assess the hypothesis that the efficiency of vital tooth bleaching depends on the concentration of carbamide peroxide agents. METHODS: The front teeth of 30 subjects were bleached at home with 10%, 17% or 0% (control) carbamide peroxide for 1 week in a double-blind study design. Tooth shades were determined in the LCH color space employing a visual shade matching system and a spectrophotometer. Differences in lightness (Deltal), chroma (Deltac) and hue (Deltah) were measured to assess the treatment process. After 2 weeks of no treatment, tooth shades were evaluated again to assess stability of the resultant shade. RESULTS: First-time changes of shade values could be observed after 3 days in the 17% group and after 7 days in the 10% group. After 1 week, in both the 17% group (Deltal: 2.80, Deltac: -3.33, Deltah: 0.60) and the 10% group (Deltal: 2.61, Deltac: -2.54, Deltah: 0.09), values for lightness and chroma were significantly different from the control (Deltal: 0.13, Deltac: 0.14, Deltah: 0.21, p<0.05) with no difference between the test groups (p>0.05). Two weeks after treatment, a rebound of shade values could be observed in the test groups (p<0.05). SIGNIFICANCE: The study indicates that higher concentration bleaching agents might whiten teeth faster with major changes in lightness and chroma. However, by bleaching daily for 1 week, similar effects can be achieved with both a high and a low concentration agent. After treatment, a regression of the resultant shade has to be expected.

Carbamide Peroxide↗

PubMed2006

Association between a variation in LRCH1 and knee osteoarthritis: a genome-wide single-nucleotide polymorphism association study using DNA pooling.

OBJECTIVE: To perform a large-scale association analysis of single-nucleotide polymorphisms (SNPs) in patients with radiographically defined osteoarthritis (OA) of the knee. METHODS: We examined >25,000 SNPs located within approximately 14,000 genes for associations with radiographically defined knee OA, using polymerase chain reaction and MassExtend amplification techniques. Allele frequencies were estimated initially in DNA pools from 335 female patients with knee OA and 335 asymptomatic and radiographically negative female control subjects. All were of northern European ancestry. Significant allele frequency differences were validated by genotyping of individual DNA samples. Confirmed significant findings were verified in 2 additional case-control samples from the UK (443 cases and 303 controls) and Newfoundland (346 cases and 264 controls). Chondrosarcoma cell lines were used to test for potential differences in gene expression. RESULTS: The marker most strongly associated with the risk of knee OA was rs912428, a C/T polymorphism in intron 1 of LRCH1, a gene on chromosome 13q14 that encodes a novel protein of as-yet-unknown function. The frequency of the T allele compared with controls was consistently increased by 40% across all 3 case-control groups. Additional subanalyses in case-control samples with hip OA and hand OA suggested similar trends, but did not reach statistical significance. Association fine-mapping using 10 additional SNPs in LRCH1 confirmed intron 1 as the region of highest association but failed to reveal variations with significance stronger than the marker SNP, as did the haplotype analysis. LRCH1 was not up-regulated or overexpressed in chondrosarcoma cell lines exposed to inflammatory stimuli, suggesting a possible structural role. CONCLUSION: A genetic variant in LRCH1 was consistently associated with knee OA in 3 samples from 2 populations. Our results also suggest that the same association with OA may exist at other sites. Additional genetic and experimental work is needed to elucidate the precise mechanism by which the LRCH1 gene influences OA risk.

Aged↗

PubMed2006

Linkage and potential association of obesity-related phenotypes with two genes on chromosome 12q24 in a female dizygous twin cohort.

Obesity is a multifactorial disorder with a complex phenotype. It is a significant risk factor for diabetes and hypertension. We assessed obesity-related traits in a large cohort of twins and performed a genome-wide linkage scan and positional candidate analysis to identify genes that play a role in regulating fat mass and distribution in women. Dizygous female twin pairs from 1,094 pedigrees were studied (mean age 47.0+/-11.5 years (range 18-79 years)). Nonparametric multipoint linkage analyses showed linkage for central fat mass to 12q24 (141 cM) with LOD 2.2 and body mass index to 8q11 (67 cM) with LOD 1.3, supporting previously established linkage data. Novel areas of suggestive linkage were for total fat percentage at 6q12 (LOD 2.4) and for total lean mass at 2q37 (LOD 2.4). Data from follow-up fine mapping in an expanded cohort of 1243 twin pairs reinforced the linkage for central fat mass to 12q24 (LOD 2.6; 143 cM) and narrowed the -1 LOD support interval to 22 cM. In all, 45 single-nucleotide polymorphisms (SNPs) from 26 positional candidate genes within the 12q24 interval were then tested for association in a cohort of 1102 twins. Single-point Monks-Kaplan analysis provided evidence of association between central fat mass and SNPs in two genes - PLA2G1B (P = 0.0067) and P2RX4 (P = 0.017). These data provide replication and refinement of the 12q24 obesity locus and suggest that genes involved in phospholipase and purinoreceptor pathways may regulate fat accumulation and distribution.

Adolescent↗

PubMed2006

Efficiency of the Vector -system compared with conventional subgingival debridement in vitro and in vivo.

OBJECTIVE: To assess the efficacy of the novel ultrasonic Vector -system system for subgingival debridement and to compare the results with conventional periodontal instrumentation in vitro and in vivo. MATERIAL AND METHODS: Forty extracted human teeth were treated in vitro: Vector -system with polishing (VP) and abrasive fluid (VA), conventional ultrasonic system (U) and hand instrument (H). At intervals of 40 s, calculus removal was assessed using a 3D laser scanning device. Eight single-rooted teeth were treated in vivo with the Vector -system or hand instruments. Subgingival plaque samples were obtained for microbiological evaluation. After extraction, residual calculus was assessed by means of digitized planimetry. RESULTS: In vitro efficiency of hand instruments was statistically higher compared with the conventional ultrasonic system (p < 0.05) and the Vector -system with no difference between U and VA (p > 0.05) and VA and VP (p > 0.05). Residual calculus following in vivo instrumentation was not different in the Vector and the hand instrument group (p > 0.05) but treatment time with the Vector -system was statistically higher (p < 0.05). A similar reduction of periopathogenic bacteria could be observed in both groups. CONCLUSION: Using the Vector -system, root surfaces can be debrided as thoroughly as with conventional instruments. However, treatment is more time consuming than conventional debridement.

Bacteroides↗

PubMed2005

Genetic polymorphisms in DPF3 associated with risk of breast cancer and lymph node metastases.

BACKGROUND: Several studies have identified rare genetic variations responsible for many cases of familial breast cancer but their contribution to total breast cancer incidence is relatively small. More common genetic variations with low penetrance have been postulated to account for a higher proportion of the population risk of breast cancer. METHODS AND RESULTS: In an effort to identify genes that influence non-familial breast cancer risk, we tested over 25,000 single nucleotide polymorphisms (SNPs) located within approximately 14,000 genes in a large-scale case-control study in 254 German women with breast cancer and 268 age-matched women without malignant disease. We identified a marker on chromosome 14q24.3-q31.1 that was marginally associated with breast cancer status (OR = 1.5, P = 0.07). Genotypes for this SNP were also significantly associated with indicators of breast cancer severity, including presence of lymph node metastases (P = 0.006) and earlier age of onset (P = 0.01). The association with breast cancer status was replicated in two independent samples (OR = 1.35, P = 0.05). High-density association fine mapping showed that the association spanned about 80 kb of the zinc-finger gene DPF3 (also known as CERD4). One SNP in intron 1 was found to be more strongly associated with breast cancer status in all three sample collections (OR = 1.6, P = 0.003) as well as with increased lymph node metastases (P = 0.01) and tumor size (P = 0.01). CONCLUSION: Polymorphisms in the 5' region of DPF3 were associated with increased risk of breast cancer development, lymph node metastases, age of onset, and tumor size in women of European ancestry. This large-scale association study suggests that genetic variation in DPF3 contributes to breast cancer susceptibility and severity.

Journal Article↗

PubMed2005

Genome-wide SNP association: identification of susceptibility alleles for osteoarthritis.

The successful identification of genes involved in common human disorders is dependent upon availability of informative sample sets, validated marker panels, a high-throughput scoring technology, and a strategy for combining these resources. We have developed a universal platform based on mass spectrometry (MassARRAY) for analyzing nucleic acids with high precision and accuracy. To fuel this technology we have generated more than 100,000 validated assays for single nucleotide polymorphisms (SNPs) covering virtually all known and predicted human genes, and a large DNA sample bank from more than 50,000 consented diseased (case) and healthy (control) individuals. Taking advantage of MassARRAY's capability for quantitative analysis of nucleic acids, allele frequencies are estimated in sample pools containing large numbers of individual DNAs. Comparing frequencies between case and control pools as a first-pass filtering step is a tremendous advantage in throughput and cost over individual genotyping. We have employed this approach in numerous genome-wide association studies to identify genes implicated in common complex diseases, including osteoarthritis (OA). Access to additional patient samples through collaborations allows us to conduct replication studies that validate true disease genes. These discoveries will expand our understanding of genetic disease predisposition, and our capabilities for early diagnosis and improved therapeutic approaches.

Alleles↗

PubMed2005

Role of ICAM1 in invasion of human breast cancer cells.

We identified previously a region on chromosome 19p13.2 spanning the genes encoding the intercellular adhesion molecules (ICAM), ICAM1, ICAM4 and ICAM5 as a breast cancer susceptibility locus. Genetic variants in this region were also associated with indicators of disease severity, including higher rates of metastases to other organs. Based on this association, we set out to explore the role of ICAM1 in proliferation and invasion of human breast cancer cells. We observed that ICAM1 downregulation at the mRNA and protein levels led to a strong suppression of human breast cell invasion through a matrigel matrix. Under the same conditions, no significant effect on cell proliferation in vitro was seen. Incubation of cells with an antibody against ICAM1 blocked invasion of the highly metastatic MDA-MB-435 cell line in a dose-dependent manner without affecting cell migration. We also demonstrated that the level of ICAM1 protein expression on the cell surface positively correlated with metastatic potential of five human breast cancer cell lines and that ICAM1 mRNA levels were elevated in breast tumor compared with adjacent normal tissue. These results corroborate our previous genetic finding that variations in the ICAM region are associated with the occurrence of metastases and establish a causal role of ICAM1 in invasion of metastatic human breast carcinoma cell lines.

Breast Neoplasms↗

PubMed2005

Association between a variation in the phosphodiesterase 4D gene and bone mineral density.

BACKGROUND: Fragility fractures caused by osteoporosis are a major cause of morbidity and mortality in aging populations. Bone mineral density (BMD) is a useful surrogate marker for risk of fracture and is a highly heritable trait. The genetic variants underlying this genetic contribution are largely unknown. METHODS: We performed a large-scale association study investigating more than 25,000 single nucleotide polymorphisms (SNPs) located within 16,000 genes. Allele frequencies were estimated in contrasting DNA pools from white females selected for low (<0.87 g/cm2, n = 319) and high (> 1.11 g/cm2, n = 321) BMD at the lumbar spine. Significant findings were verified in two additional sample collections. RESULTS: Based on allele frequency differences between DNA pools and subsequent individual genotyping, one of the candidate loci indicated was the phosphodiesterase 4D (PDE4D) gene region on chromosome 5q12. We subsequently tested the marker SNP, rs1498608, in a second sample of 138 white females with low (<0.91 g/cm2) and 138 females with high (>1.04 g/cm2) lumbar spine BMD. Odds ratios were 1.5 (P = 0.035) in the original sample and 2.1 (P = 0.018) in the replication sample. Association fine mapping with 80 SNPs located within 50 kilobases of the marker SNP identified a 20 kilobase region of association containing exon 6 of PDE4D. In a second, family-based replication sample with a preponderance of females with low BMD, rs1498608 showed an opposite relationship with BMD at different sites (p = 0.00044-0.09). We also replicated the previously reported association of the Ser37Ala polymorphism in BMP2, known to interact biologically with PDE4D, with BMD. CONCLUSION: This study indicates that variants in the gene encoding PDE4D account for some of the genetic contribution to bone mineral density variation in humans. The contrasting results from different samples indicate that the effect may be context-dependent. PDE4 inhibitors have been shown to increase bone mass in normal and osteopenic mice, but up until now there have been no reports implicating any member of the PDE4 gene family in human osteoporosis.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2005

Association of the NuMA region on chromosome 11q13 with breast cancer susceptibility.

The development of breast cancer is a complex process that involves multiple genes at many stages, from initial cell cycle dysregulation to disease progression. To identify genetic variations that influence this process, we conducted a large-scale association study using a collection of German cases and controls and >25,000 SNPs located within 16,000 genes. One of the loci identified was located on chromosome 11q13 [odds ratio (OR)=1.85, P=0.017]. The initial association was subsequently tested in two independent breast cancer collections. In both sample sets, the frequency of the susceptibility allele was increased in the cases (OR=1.6, P=0.01). The susceptibility allele was also associated with an increase in cancer family history (P=0.1). Fine mapping showed that the region of association extends approximately 300 kb and spans several genes, including the gene encoding the nuclear mitotic apparatus protein (NuMA). A nonsynonymous SNP (A794G) in NuMA was identified that showed a stronger association with breast cancer risk than the initial marker SNP (OR=2.8, P=0.005 initial sample; OR=2.1, P=0.002 combined). NuMA is a cell cycle-related protein essential for normal mitosis that is degraded in early apoptosis. NuMA-retinoic acid receptor alpha fusion proteins have been described in acute promyelocytic leukemia. Although the potential functional relevance of the A794G variation requires further biological validation, we conclude that variations in the NuMA gene are likely responsible for the observed increased breast cancer risk.

Adult↗

PubMed2005

BRAF polymorphisms and risk of melanocytic neoplasia.

Somatic mutations of the BRAF gene are common in melanomas and nevi but the contribution of polymorphisms in this gene to melanoma or nevus susceptibility remains unclear. An Australian melanoma case-control sample was typed for 16 single nucleotide polymorphisms (SNP) within the BRAF gene, and five SNP in three neighboring genes. The sample comprised 755 melanoma cases from 740 families stratified by family history of melanoma and controls from 635 unselected twin families (2,239 individuals). Ancestry of the cases and controls was recorded, and the twins had undergone skin examination to assess total body nevus count, degree of freckling, and pigmentation phenotype. Genotyping was carried out via primer extension followed by matrix-assisted laser desorption ionization-time of flight mass spectrometry. SNP in the BRAF gene were found to be weakly associated with melanoma status but not with development of nevi or freckles. The estimated proportion of attributable risk of melanoma due to variants in BRAF is 1.6%. This study shows that BRAF polymorphisms predispose to melanoma but the causal variant has yet to be determined. The burden of disease associated with this variant is greater than that associated with the major melanoma susceptibility locus CDKN2A, which has an estimated attributable risk of 0.2%.

Diseases in Twins↗

PubMed2005

Removal of root substance with the Vector-system compared with conventional debridement in vitro.

OBJECTIVE: The aim of the present study was to assess the removal of root substance with the Vector-system depending on different irrigation fluids and to compare the results with conventional methods for root debridement. MATERIAL AND METHODS: Forty extracted human teeth were treated using four different methods: Vector-system with polishing fluid and metal curette (VP), Vector-system with abrasive fluid and metal curette (VA), conventional ultrasonic system (U) with insert tip "P" and hand instrument. Treatment of the calculus-free root surfaces was carried out for a total of 12 min. using an artificial periodontal pocket. At intervals of 120 s, the removal of dental hard tissues was assessed using a three-dimensional (3D) laser scanning device and the Match 3D software with an accuracy of 0.00001 mm(3). RESULTS: No difference in the removal of root substance with the hand instrument (0.0055 mm(3)/s) and the Vector-system using the abrasive fluid (0.0044 mm(3)/s) could be observed (p=0.51). Using these two systems, a larger amount of root substance (p<0.05) was removed compared with the other methods (U: 0.0023 mm(3)/s, VP: 0.0022 mm(3)/s), which did not differ from each other (p=0.76). CONCLUSIONS: The present study indicates that the Vector-system in combination with polishing fluid or conventional ultrasonics might be used for root debridement without extensive root substance removal.

Dental Cementum↗

PubMed2005

Efficiency of subgingival calculus removal with the Vector-system compared to ultrasonic scaling and hand instrumentation in vitro.

OBJECTIVE: The recently introduced Vector-system (Duerr Dental, Bietigheim-Bissingen, Germany) is recommended to be used in conjunction with different insert tips and irrigation fluids. The aim of the study was to assess subgingival calculus removal depending on the mode of operation and to compare the results to conventional methods for root debridement. METHODS: Sixty extracted human teeth with calculus on the root surface were treated in an artificial periodontal pocket model using six methods: Vector-system with metal probe insert (VPP) or metal curette insert (VPC), both used with polishing fluid, Vector-system with metal probe insert (VAP) or metal curette insert (VAC), both used with abrasive fluid, EMS-ultrasonic system (U) and hand instrument (Gracey curette). Photographs of the root surface were taken at intervals of 10 s and calculus removal was assessed using a surface analysis software until the root surfaces were cleaned completely. Analysis of variances (ANOVA) of the ranks with subsequent comparison of mean ranks and calculation of homogeneous groups (Scheffe) were used for statistical analysis. RESULTS: Employing the hand instrument, highest efficiency could be observed (0.340 mm2/s). Calculus removal with the Vector-system and metal probe insert (VPP: 0.036 mm2/s; VAP: 0.067 mm2/s) was less effective (p < 0.05) than using the system with metal curette inserts (VPC: 0.122 mm2/s; VAC: 0.209 mm2/s). Employing the abrasive fluid, removal of deposits with the metal curette insert was as efficient as with the conventional ultrasonic system (U: 0.199 mm2/s, p > 0.05). CONCLUSION: The present in vitro study indicates that the efficiency of calculus removal with the Vector-system is significantly dependent on the selection of inserts and irrigation fluids.

Analysis of Variance↗

PubMed2005

Genetic analysis of candidate modifier polymorphisms in Hb E-beta 0-thalassemia patients.

Hemoglobin E (Hb E)-beta-thalassemia patients display a range of clinical severities, from nearly asymptomatic to transfusion-dependent thalassemia major. Given this clinical heterogeneity, additional genetic factors modifying disease severity remain to be discovered. Association studies are being conducted to elucidate the role of genetic polymorphisms as disease severity modifiers in Hb E-beta-thalassemia patients. Using strict scoring criteria, 1060 Hb E-beta-thalassemia patients were categorized into mild, moderate, and severe groups. Taking a candidate gene approach, we found no statistically significant differences between the mild and severe patients groups in allelic or genotypic frequencies for single nucleotide polymorphisms within five genes known to influence globin gene expression and erythropoiesis.

Adolescent↗

PubMed2005

Detection of subgingival calculus with a novel LED-based optical probe.

BACKGROUND: A recently introduced detection device is designed for objective subgingival calculus diagnosis. The aim of the present study was to assess the possibility of detecting subgingival calculus with this novel LED-based optical probe in vitro. METHODS: Twenty extracted human teeth with calculus on the root surface were fixed on a translation stage. Measurements on the root surface were carried out in increments of 0.25 mm with an angulation of 0 to 10 degrees , 45 degrees , or 90 degrees to the optical fiber. Teeth were covered either with sodium chloride (NaCl) or blood in order to determine the influence of ambient fluids. Successional areas of positive measurements were defined as "length of positive values" (LPV). The results were compared to the clinical and histological findings. RESULTS: Clinically and histologically apparent calculus on the root surface was accompanied by positive measurement values. A reduction of the angulation between probe and root surface resulted in shorter LPV when measurements were performed in blood (P <0.05) and longer LPV employing NaCl as the ambient fluid (P <0.05). For both blood and NaCl, sensitivity and/or specificity values decreased when using lower angulations. CONCLUSION: The optical probe offers the possibility of subgingival calculus detection and may, therefore, be suited to determine the endpoint of root surface instrumentation during non-surgical periodontal therapy.

Dental Calculus↗

PubMed2004

Large-scale association study identifies ICAM gene region as breast and prostate cancer susceptibility locus.

We conducted a large-scale association study to identify genes that influence nonfamilial breast cancer risk using a collection of German cases and matched controls and >25,000 single nucleotide polymorphisms located within 16,000 genes. One of the candidate loci identified was located on chromosome 19p13.2 [odds ratio (OR) = 1.5, P = 0.001]. The effect was substantially stronger in the subset of cases with reported family history of breast cancer (OR = 3.4, P = 0.001). The finding was subsequently replicated in two independent collections (combined OR = 1.4, P < 0.001) and was also associated with predisposition to prostate cancer in an independent sample set of prostate cancer cases and matched controls (OR = 1.4, P = 0.002). High-density single nucleotide polymorphism mapping showed that the extent of association spans 20 kb and includes the intercellular adhesion molecule genes ICAM1, ICAM4, and ICAM5. Although genetic variants in ICAM5 showed the strongest association with disease status, ICAM1 is expressed at highest levels in normal and tumor breast tissue. A variant in ICAM5 was also associated with disease progression and prognosis. Because ICAMs are suitable targets for antibodies and small molecules, these findings may not only provide diagnostic and prognostic markers but also new therapeutic opportunities in breast and prostate cancer.

Adult↗