Brittle Culm1, a COBRA-Like Protein,Functions in Cellulose Assembly through Binding Cellulose Microfibrils

Cellulose represents the most abundant biopolymer in nature and has great economic importance. Cellulose chains pack laterally into crystalline forms, stacking into a complicated crystallographic structure. However, the mechanism of cellulose crystallization is poorly understood. Here, via functional characterization, we report that Brittle Culm1 (BC1), a COBRA-like protein in rice, modifies cellulose crystallinity. BC1 was demonstrated to be a glycosylphosphatidylinositol (GPI) anchored protein and can be released into cell walls by removal of the GPI anchor. BC1 possesses a carbohydrate-binding module (CBM) at its N-terminus. In vitro binding assays showed that this CBM interacts specifically with crystalline cellulose, and several aromatic residues in this domain are essential for binding. It was further demonstrated that cell wall-localized BC1 via the CBM and GPI anchor is one functional form of BC1. X-ray diffraction (XRD) assays revealed that mutations in BC1 and knockdown of BC1 expression decrease the crystallite width of cellulose; overexpression of BC1 and the CBM-mutated BC1s caused varied crystallinity with results that were consistent with the in vitro binding assay. Moreover, interaction between the CBM and cellulose microfibrils was largely repressed when the cell wall residues were pre-stained with two cellulose dyes. Treating wild-type and bc1 seedlings with the dyes resulted in insensitive root growth responses in bc1 plants. Combined with the evidence that BC1 and three secondary wall cellulose synthases (CESAs) function in different steps of cellulose production as revealed by genetic analysis, we conclude that BC1 modulates cellulose assembly by interacting with cellulose and affecting microfibril crystallinity.     

Environmental stress as an indicator of anthropogenic impact across the African Albertine Rift: a case study using museum specimens

We examined fluctuating asymmetry (FA) and body condition (BC) as two measures of environmental stress using museum specimens of Lophuromys aquilus, a rodent species complex wide-spread across the African Albertine Rift. We related FA and BC to a spatially-derived index of anthropogenic impact using a principal components analysis (PCA). We found no relationship between the four PCA scores and mean FA or BC, but did find that FA variance was higher in areas with lower anthropogenic impact. There was also a negative, albeit non-significant, trend for PC3, suggesting that populations with higher than average BC were in areas with higher anthropogenic impact. Overall, our case study does not support FA and BC as effective predictors of environmental stress with low to moderate habitat disturbance. In fact, L. aquilus, as a habitat generalist, may be positively affected by some aspects of anthropogenic change. Studies relating environmental stress to anthropogenic impact should examine sites with a wide range of habitat qualities and human impact and utilize multiple measures of environmental stress to characterize the health of one or more populations.     

Effect of dietary Bacillus coagulans on the performance and intestinal microbiota of weaned piglets

The performance of weaned piglets suffers from severe limitations resulting from diarrhoea. Therefore, this trial was performed to investigate the effects of Bacillus coagulans as an alternative to antibiotics on piglet growth performance and intestinal health. Ninety (initial BW = 7.70 ± 0.17 kg, weaning age of 26 days) healthy weaned piglets with similar BWs were selected and randomised into three treatment groups. Pigs in the negative control (NC) group were fed a basal diet, pigs in the positive control (PC) group were fed the basal diet plus antibiotics, and pigs in the test group (BC) were fed the basal diet plus Bacillus coagulans at 600 g/t; the trial lasted for 28 days. The results showed that the ratios of feed to gain (F:G) of both the BC and PC groups from 1 to 21 days were significantly lower (P < 0.05), and the average daily weight gain (ADG) of the BC group from 22 to 28 days was significantly higher (P < 0.05) than that of the NC group in terms of growth performance. The diarrhoea index was lowest in the PC group, followed by the BC group, and highest in the NC group. The BC group had a lower diarrhoea index at the later stage. We performed 16S rRNA sequencing to measure the intestinal bacteria and found that the BC group had a higher intestinal bacteria diversity than the NC and PC groups (P < 0.05). From days 1 to 21, the main differential species were Ruminococcaceae_UCG-014 and Faecalibacterium (P < 0.05); from days 22 to 28, the main differential species were Prevotella_9, unclassified_f__Lachnospiraceae, Anaerovibrio, and Ruminococcaceae_UCG-002 (P < 0.05). The correlation analysis between growth performance and species revealed specific gut microorganisms responsible for variation in F:G, ADG, and diarrhoea index, such as Prevotellaceae, Clostridium_sensu_stricto_1, Ruminococcaceae, Phascolarctobacterium, and Anaerovibrio. In conclusion, Bacillus coagulans changed the microbial composition in the faeces of weaned piglets, which had positive effects on growth performance and the diarrhoea index. Therefore, our study provided new insight into the future application of Bacillus coagulans as an additive.     

Distribution of bronchoconstrictor responses in isolated-perfused rat lung

We studied the effects of bronchoconstrictor stimuli administered selectively through isolated-perfused preparations of the bronchial and pulmonary circulations of 80 Sprague-Dawley rats. Dose-related contraction was elicited with infusion of acetylcholine (ACh), histamine, and serotonin (5-HT). Bolus infusion of 10(-5) mol ACh caused a 3.5-fold increase in pulmonary resistance (RL) after infusion into the pulmonary circulation (PC) and a 2.5-fold increase in the bronchial circulation (BC) (P less than 0.05 vs. control) that was blocked selectively in each circulation with atropine. Administration of 10(-5) mol 5-HT into the BC caused only a 45% increase in RL; the same dose of 5-HT caused a 5.1-fold increase in RL in the PC. A biphasic (increase at lower doses/decrease at higher doses) change in RL was elicited by histamine that was converted to dose-related constriction after H2-receptor blockade with cimetidine in both BC and PC. Response to exogenous ACh remained viable for greater than 5 h. Infusion of the mast cell degranulating agent, compound 48/80 (48/80), caused increase in RL that corresponded to quantitative recovery of histamine in the perfusates of both BC and PC. Histamine concentration in the perfusate increased from 47.2 +/- 31.8 (base line) to 624 +/- 60.1 ng/ml (2-fold increase in RL) in the BC and from 38.3 +/- 17.7 (base line) to 294.4 +/- 38.1 ng/ml (50% increase in RL) in the PC (P less than 0.001 vs. baseline concentration) after a 0.1-mg/ml dose of 48/80.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of the roles of estrogens and androgens in breast cancer and prostate cancer

Breast cancer (BC) and prostate cancer (PC) are the second most common malignant tumors in women and men in western countries, respectively. The risks of death are 14% for BC and 9% for PC. Abnormal estrogen and androgen levels are related to carcinogenesis of the breast and prostate. Estradiol stimulates cancer development in BC. The effect of estrogen on PC is concentration-dependent, and estrogen can regulate androgen production, further affecting PC. Estrogen can also increase the risk of androgen-induced PC. Androgen has dual effects on BC via different metabolic pathways, and the role of the androgen receptor (AR) in BC also depends on cell subtype and downstream target genes. Androgen and AR can stimulate both primary PC and castration-resistant PC. Understanding the mechanisms of the effects of estrogen and androgen on BC and PC may help us to improve curative BC and PC treatment strategies.     

Role of Efflux Pumps in Adaptation and Resistance of Listeria monocytogenes to Benzalkonium Chloride

In this study, potential mechanisms underlying resistance and adaptation to benzalkonium chloride (BC) in Listeria monocytogenes were investigated. Two groups of strains were studied. The first group consisted of strains naturally sensitive to BC which could be adapted to BC. The second group consisted of naturally resistant strains. For all adapted isolates, there was a correlation between the resistance to BC and ethidium bromide, but this was not the case for the naturally resistant isolates. To investigate the role of efflux pumps in adaptation or resistance, reserpine, an efflux pump inhibitor, was added to the strains. Addition of reserpine to the sensitive and adapted strains resulted in a decrease in the MIC for BC, whereas no such decrease was observed for the resistant strains, indicating that efflux pumps played no role in the innate resistance of certain strains of L. monocytogenes to this compound. Two efflux pumps (MdrL and Lde) have been described in L. monocytogenes. Studies showed low and intermediate levels of expression of the genes encoding the efflux pumps for two selected resistant strains, H7764 and H7962, respectively. Adaptation to BC of sensitive isolates of L. monocytogenes resulted in significant increases in expression of mdrl (P < 0.05), but no such increase was observed for lde for two adapted strains of L. monocytogenes, LJH 381 (P = 0.91) and C719 (P = 0.11). This indicates that the efflux pump Mdrl is at least partly responsible for the adaptation to BC.     

Preparation of cellulose films from solution of bacterial cellulose in NMMO

Bacterial cellulose (BC) was dissolved in N-methylmorpholine N-oxide (NMMO) to prepare regenerated BC films (RBC) with phase inversion. The solubility of BC, supermolecule on structure, morphology, thermal and physical properties of the films were investigated by Fourier transform infrared spectroscopy (FT-IR), solid-state cross polarization/magic angle spinning ¹³C nuclear magnetic resonance (CP/MAS ¹³C NMR), wide-angle X-ray diffraction (WAXD), scanning electron microscope (SEM), and thermogravimetric analysis (TGA). The investigation suggested BC was dissolved completely in NMMO. From the C₆ signal shifts to the amorphous area, the crystallinity of materials decreased from 79.20% to 38.17%, and the transformation from cellulose I to II occurred. It was also found that the banded structure of the native materials was replaced by homogeneous and densified sections, so RBC films had better mechanical and barrier properties, and do thermal stability was similar to that of the native BC.     

Synergistic effects of hormone therapy drugs and usnic acid on hormone receptor‐positive breast and prostate cancer cells

The aim of this study was to investigate the combined effects of usnic acid (UA) and Tamoxifen (Tam) or Enzalutamide (Enz) on hormone receptor‐positive breast and prostate cancer (BC and PC), respectively. The antiproliferative and apoptotic effects of Tam or Enz alone and in combination with UA on MCF7 and LNCaP cancer cells were detected. The results of the WST‐1 assay indicated that UA was a promising anticancer compound that significantly enhanced the effectiveness of hormone therapy drugs compared with each drug alone (combination index < 1). In addition, the combination of UA with Tam or Enz remarkably induced more cell cycle arrest at the G0/G1 phase and apoptosis than only drug‐treated cells (P < 0.01). Consequently, our findings suggest that the combination of UA with Tam or Enz may be a potential therapeutic approach for the treatment of BC and PC and further studies are required to exploit the potential mechanisms of synergistic effects.     

Analysis of Gut Microbiota in Patients with Breast Cancer and Benign Breast Lesions

Breast cancer (BC) and benign breast lesions (BBLs) are common diseases in women worldwide. The gut microbiota plays a vital role in regulating breast diseases’ formation, progression, and therapy response. Hence, we explored the structure and function of gut microflora in patients with BC and BBLs. A cohort of 66 subjects was enrolled in the study. Twenty-six subjects had BC, 20 subjects had BBLs, and 20 matched healthy controls. High throughput 16S ribosomal RNA (16S rRNA) gene sequencing technology was used to determine the microbial community structure. Compared with healthy individuals, BC patients had significantly lower alpha diversity indices (Sobs index, p = 0.019; Chao1 index, p = 0.033). Sobs and Chao1 indices were also lower in patients with BBLs than healthy individuals, without statistical significance (p = 0.279, p = 0.314, respectively). Both unweighted and weighted UniFrac analysis showed that beta diversity differed significantly among the three groups (p = 3.376e–14, p < 0.001, respectively). Compared with healthy individuals, the levels of Porphyromonas and Peptoniphilus were higher in BC patients (p = 0.004, p = 0.007, respectively), whereas Escherichia and Lactobacillus were more enriched in the benign breast lesion group (p < 0.001, p = 0.011, respectively). Our study indicates that patients with BC and BBLs may undergo significant changes in intestinal microbiota. These findings can help elucidate the role of intestinal flora in BC and BBLs patients. Open in a separate window     

Estrogen receptor alpha (ERS1) SNPs c454-397T>C (PvuII) and c454-351A>G (XbaI) are risk biomarkers for breast cancer development

There are several risk factors related to Breast Cancer (BC) risks and response to chemotherapy with SERMs. Recently some single nucleotide polymorphisms (SNPs) on ESR1 gene have been associated to this disease. However, data are still inconclusive. The present study aimed to investigate the association of SNPs c454-397T>C (also called PvuII) and c454-351A>G (so called XbaI) to incidence of sporadic BC; ERα expression in BC; tamoxifen hormonetherapy (HT-TMX) responsiveness. To do so, a cohort of BC patients was analyzed through retrospective data collection, immunohistochemistry to ERα protein, and genotyping for PvuII and XbaI SNPs by PCR–RFLP, confirmed by sequencing. Significant difference in PvuII alleles frequencies were found BC patients when compared to control samples. Patients with P allele have a 5.14-fold increased BC risk. We found higher P and X alleles frequencies in ERα positive BC and the pp and xx genotypes were observed exclusively in patients with HT-TMX-responsive BC. Taken together, data indicates that P allele as a novel sporadic BC biomarker whereas p and x alleles enhanced chemotherapy responsiveness.     

MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage, lymph node metastasis and patient poor prognosis

To investigate the global expression profile of miRNAs in primary breast cancer (BC) and normal adjacent tumor tissues (NATs) and its potential relevance to clinicopathological characteristics and patient survival, the genome-wide expression profiling of miRNAs in BC was investigated using a microarray containing 435 mature human miRNA oligonucleotide probes. Nine miRNAs of hsa-miR-21, hsa-miR-365, hsa-miR-181b, hsa-let-7f, hsa-miR-155, hsa-miR-29b, hsa-miR-181d, hsa-miR-98, and hsa-miR-29c were observed to be up-regulated greater than twofold in BC compared with NAT, whereas seven miRNAs of hsa-miR-497, hsa-miR-31, hsa-miR-355, hsa-miR-320, rno-mir-140, hsa-miR-127 and hsa-miR-30a-3p were observed to be down-regulated greater than twofold. The most significantly up-regulated miRNAs, hsa-mir-21 (miR-21), was quantitatively analyzed by TaqMan real-time PCR in 113 BC tumors. Interestingly, among the 113 BC cases, high level expression of miR-21 was significantly correlated with advanced clinical stage (P = 0.006, Fisher's exact text), lymph node metastasis (P = 0.007, Fisher's exact text), and shortened survival of the patients (hazard ratio [HR]=5.476, P < 0.001). Multivariate Cox regression analysis revealed this prognostic impact (HR=4.133, P = 0.001) to be independent of disease stage (HR=2.226, P = 0.013) and histological grade (HR=3.681, P = 0.033). This study could identify the differentiated miRNAs expression profile in BC and reveal that miR-21 overexpression was correlated with specific breast cancer biopathologic features, such as advanced tumor stage, lymph node metastasis, and poor survival of the patients, indicating that miR-21 may serve as a molecular prognostic marker for BC and disease progression.     

Predictive coding accounts for V1 response properties recorded using reverse correlation

PC/BC (“Predictive coding/Biased competition”) is a simple computational model that has previously been shown to explain a very wide range of V1 response properties. This article extends work on the PC/BC model of V1 by showing that it can also account for V1 response properties measured using the reverse correlation methodology. Reverse correlation employs an experimental procedure that is significantly different from that used in more typical neurophysiological experiments, and measures some distinctly different response properties in V1. Despite these differences PC/BC successfully accounts for the data. The current results thus provide additional support for the PC/BC model of V1 and further demonstrate that PC/BC offers a unified explanation for the seemingly diverse range of behaviours observed in primary visual cortex.     

Contribution of changes in demography and in the risk factors to the predicted pattern of cancer mortality among Spanish women by 2022

BackgroundChanges in the burden of cancer mortality are expected to be observed among Spanish women. We predict those changes, in Spain, for breast cancer (BC), colorectal cancer (CRC), lung cancer (LC) and pancreatic cancer (PC) from 2013 to 2022.MethodsBayesian age–period–cohort modeling was used to perform projections of the cancer burden in 2013–2022, extrapolating the trend of cancer mortality data from 1998 to 2012. We assessed the time trends of the crude rates (CRs) during 1998–2012, and compared the number of cancer deaths between the periods 2008–2012 and 2018–2022 to assess the contribution of demographic changes and changes in the risk factors for cancer.ResultsDuring 1998–2012, CRs of cancer decreased for BC (0.3% per year) and increased for LC (4.7%), PC (2%) and CRC (0.7%). During 2013–2022, CRs might level off for CRC, whereas the time trends for the remaining cancers might continue at a similar pace. During 2018–2022, BC could be surpassed by CRC as the most frequent cause of cancer mortality among Spanish women, whereas LC could be the most common cause of cancer mortality among women aged 50–69 years (N/year = 1960 for BC versus N/year = 1981 for LC). Comparing 2018–2022 and 1998–2012, changes in the risk factors for cancer could contribute 37.93% and 18.36% to the burden of LC and PC, respectively, and demographic shifts – mainly due to ageing (19.27%) – will drive the burden of CRC.ConclusionsDuring 2018–2022, demographic changes (ageing) and changes in risk factors could have a different impact on the lifetime risk of cancer among Spanish women.     

Development of candidate gene markers associated to common bacterial blight resistance in common bean

Common bacterial blight (CBB), caused by Xanthomonas axonopodis pv. phaseoli (Xap), is a major yield-limiting factor of common bean (Phaseolus vulgaris L.) production around the world. Two major CBB-resistant quantitative trait loci (QTL), linked to the sequence characterized amplified region markers BC420 and SU91, are located at chromosomes 6 and 8, respectively. Using map-based cloning approach, four bacterial artificial chromosome (BAC) clones from the BC420-QTL locus and one BAC clone containing SU91 were sequenced by Roche 454 technique and subsequently assembled using merged assemblies from three different programs. Based on the quality of the assembly, only the sequences of BAC 32H6 and 4K7 were used for candidate gene marker (CGM) development and candidate gene (CG) selection. For the BC420-QTL locus, 21 novel genes were predicted in silico by FGENESH using Medicago gene model, whereas 16 genes were identified in the SU91-QTL locus. For each putative gene, one or more primer pairs were designed and tested in the contrasting near isogenic lines. Overall, six and nine polymorphic markers were found in the SU91- and BC420-QTL loci, respectively. Afterwards, association mapping was conducted in a breeding population of 395 dry bean lines to discover marker-trait associations. Two CGMs per each locus showed better association with CBB resistance than the BC420 and SU91 markers, which include BC420-CG10B and BC420-CG14 for BC420_QTL locus, and SU91-CG10 and SU91-CG11 for SU91_QTL locus. The strong associations between CBB resistance and the CGs 10 and 14 from BC420_QTL locus and the CGs 10 and 11 from SU91_QTL locus indicate that the genes 10 and 14 from the BC420 locus are potential CGs underlying the BC420_QTL locus, whereas the genes 10 and 11 from the SU91 locus are potential CGs underlying the SU91_QTL locus. The superiority of SU91-CG11 was further validated in a recombinant inbred line population Sanilac?×?OAC 09-3. Thus, co-dominant CGMs, BC420-CG14 and SU91-CG11, are recommended to replace BC420 and SU91 for marker-assisted selection of common bean with resistance to CBB.     

Downregulation of MTAP promotes Tumor Growth and Metastasis by regulating ODC Activity in Breast Cancer

5''-Methylthioadenosine phosphorylase (MTAP) is a key enzyme in the methionine salvage pathway and has been reported to suppress tumorigenesis. The MTAP gene is located at 9p21, a chromosome region often deleted in breast cancer (BC). However, the clinical and biological significance of MTAP in BC is still unclear. Here, we reported that MTAP was frequently downregulated in 41% (35/85) of primary BCs and 89% (8/9) of BC cell lines. Low expression of MTAP was significantly correlated with a poor survival of BC patients (P=0.0334). Functional studies showed that MTAP was able to suppress both in vitro and in vivo tumorigenic ability of BC cells, including migration, invasion, angiogenesis, tumor growth and metastasis in nude mice with orthotopic xenograft tumor of BC. Mechanistically, we found that downregulation of MTAP could increase the polyamine levels by activating ornithine decarboxylase (ODC). By treating the MTAP-repressing BC cells with specific ODC inhibitor Difluoromethylornithine (DFMO) or treating the MTAP-overexpressing BC cells with additional putrescine, metastasis-promoting or -suppressing phenotype of these MTAP-manipulated cells was significantly reversed, respectively. Taken together, our data suggested that MTAP has a critical metastasis-suppressive role by tightly regulating ODC activity in BC cells, which may serve as a prominent novel therapeutic target for advanced breast cancer treatment.     

Viability and cellulose synthesizing ability of Gluconacetobacter xylinus cells under high-hydrostatic pressure

The effect of pressure on viability and the synthesis of bacterial cellulose (BC) by Gluconacetobacter xylinus ATCC53582 were investigated. G. xylinus was statically cultivated in a pressurized vessel under 0.1, 30, 60, and 100 MPa at 25°C for 6 days. G. xylinus cells remained viable and retained cellulose producing ability under all the conditions tested, though the production of cellulose decreased with increasing the pressure. The BCs produced at each pressure condition were analyzed by field emission scanning electron microscopy (FE-SEM) and Fourier Transform Infrared (FT-IR). FE-SEM revealed that the widths of BC fibers produced under high pressure decreased as compared with those produced under the atmospheric pressure. By FT-IR, all the BCs were found to be of Cellulose type I, as the same as typical native cellulose. Our findings evidently showed that G. xylinus possessed a piezotolerant (barotolerant) feature adapting to 100 MPa without losing its BC producing ability. This was the first attempt in synthesizing BC with G. xylinus under elevated pressure of 100 MPa, which corresponded to the deep sea at 10,000 m.     

Vesicular and nonvesicular transport of phosphatidylcholine in polarized HepG2 cells

We have investigated the transport and canalicular enrichment of fluorescent phosphatidylcholine (PC) in HepG2 cells using the fluorescent analogs of PC C6-NBD-PC and β-BODIPY-PC. Fluorescent PC was efficiently transported to the biliary canaliculus (BC) and became enriched on the lumenal side of the canalicular membrane as shown for C6-NBD-PC. Some fluorescent PC was transported in vesicles to a subapical compartment (SAC) or apical recycling compartment (ARC) in polarized HepG2 cells as shown by colocalization with fluorescent sphingomyelin (C6-NBD-SM) and fluorescent transferrin, respectively. Extensive trafficking of vesicles containing fluorescent PC between the basolateral domain, the SAC/ARC and the BC as well as endocytosis of PC analogs from the canalicular membrane were found. Evidence for nonvesicular transport included enrichment of the PC-analog β-BODIPY-PC in the BC (t_1/2 = 3.54 min) prior to its accumulation in the SAC/ARC (t_1/2 = 18.5 min) at 37 °C. Transport of fluorescent PC to the canalicular membrane also continued after disruption of the actin or microtubule cytoskeleton and at 2 °C. These results indicate that: (i) a nonvesicular transport pathway significantly contributes to the canalicular enrichment of PC in hepatocytic cells, and (ii) vesicular transport of fluorescent PC occurs from both membrane domains via the SAC/ARC.     

Changes in Body Composition in Anorexia Nervosa: Predictors of Recovery and Treatment Outcome

The restoration of body composition (BC) parameters is considered to be one of the most important goals in the treatment of patients with anorexia nervosa (AN). However, little is known about differences between AN diagnostic subtypes [restricting (AN-R) and binge/purging (AN-BP)] and weekly changes in BC during refeeding treatment. Therefore, the main objectives of our study were twofold: 1) to assess the changes in BC throughout nutritional treatment in an AN sample and 2) to analyze predictors of BC changes during treatment, as well as predictors of treatment outcome. The whole sample comprised 261 participants [118 adult females with AN (70 AN-R vs. 48 AN-BP), and 143 healthy controls]. BC was measured weekly during 15 weeks of day-hospital treatment using bioelectrical impedance analysis (BIA). Assessment measures also included the Eating Disorders Inventory-2, as well as a number of other clinical indices. Overall, the results showed that AN-R and AN-BP patients statistically differed in all BC measures at admission. However, no significant time×group interaction was found for almost all BC parameters. Significant time×group interactions were only found for basal metabolic rate (p = .041) and body mass index (BMI) (p = .035). Multiple regression models showed that the best predictors of pre-post changes in BC parameters (namely fat-free mass, muscular mass, total body water and BMI) were the baseline values of BC parameters. Stepwise predictive logistic regressions showed that only BMI and age were significantly associated with outcome, but not with the percentage of body fat. In conclusion, these data suggest that although AN patients tended to restore all BC parameters during nutritional treatment, only AN-BP patients obtained the same fat mass values as healthy controls. Put succinctly, the best predictors of changes in BC were baseline BC values, which did not, however, seem to influence treatment outcome.     

Evidence for a rare prostate cancer-susceptibility locus at chromosome 1p36

Combining data from a genomic screen in 70 families with a high risk for prostate cancer (PC) with data from candidate-region mapping in these families and an additional 71 families, we have localized a potential hereditary PC-susceptibility locus to chromosome 1p36. Because an excess of cases of primary brain cancer (BC) have been observed in some studies of families with a high risk for PC, and because loss of heterozygosity at 1p36 is frequently observed in BC, we further evaluated 12 families with both a history of PC and a blood relative with primary BC. The overall LOD score in these 12 families was 3.22 at a recombination fraction (theta) of .06, with marker D1S507. On the basis of an a priori hypothesis, this group was stratified by age at diagnosis of PC. In the younger age group (mean age at diagnosis <66 years), a maximum two-point LOD score of 3.65 at straight theta = .0 was observed, with D1S407. This linkage was rejected in both early- and late-onset families without a history of BC (LOD scores -7.12 and -6.03, respectively, at straight theta = .0). After exclusion of 3 of the 12 families that had better evidence of linkage to previously described PC-susceptibility loci, linkage to the 1p36 region was suggested by a two-point LOD score of 4.74 at straight theta = .0, with marker D1S407. We conclude that a significant proportion of these families with both a high risk for PC and a family member with BC show linkage to the 1p36 region.