Propolis is increasingly being discussed as an alternative to commonly used antiseptics. This in vitro study focused on the ethanolic extract of green Brazilian propolis (EEPg) as an additive in an ...oral health care product. We investigated (i) a potential inflammation-modulation activity of EEPg when a periodontal or Candida biofilm was exposed to monocytic (MONO-MAC-6) cells, (ii) the adhesion of oral pathogens to gingival keratinocytes and (iii) the antimicrobial and antibiofilm effect of different toothpaste formulations. EEPg decreased the levels of interleukin (IL)-1β and increased IL-10 in MONO-MAC cells challenged with a periodontal biofilm. In contact with TIGK cells, EEPg reduced the numbers of adherent
to 0.5% but did not affect the adhesion of
. The frequent brushing of a cariogenic biofilm with a toothpaste supplemented with EEPg reduced the surface microhardness loss of enamel specimens. Mixing an experimental erythritol toothpaste with 25 and 50 mg/mL of EEPg confirmed the antibacterial activity of EEPg against oral bacteria and particularly inhibited periodontal biofilm formation. The suggested toothpaste formulations seem to have potential in the prevention of caries, gingivitis and periodontitis and should be evaluated in further in vitro research and in clinical trials.
The first International Workshop of the
ATM
and Cancer Risk group focusing on the role of
Ataxia-Telangiectasia Mutated
(
ATM
) gene in cancer was held on December 4 and 5, 2019 at Institut Curie in ...Paris, France. It was motivated by the fact that germline
ATM
pathogenic variants have been found to be associated with different cancer types. However, due to the lack of precise age-, sex-, and site-specific risk estimates, no consensus on management guidelines for variant carriers exists, and the clinical utility of
ATM
variant testing is uncertain. The meeting brought together epidemiologists, geneticists, biologists and clinicians to review current knowledge and on-going challenges related to
ATM
and cancer risk. This report summarizes the meeting sessions content that covered the latest results in family-based and population-based studies, the importance of accurate variant classification, the effect of radiation exposures for
ATM
variant carriers, and the characteristics of ATM-deficient tumors. The report concludes that
ATM
variant carriers outside of the context of Ataxia-Telangiectasia may benefit from effective cancer risk management and therapeutic strategies and that efforts to set up large-scale studies in the international framework to achieve this goal are necessary.
Breast cancer risks conferred by many germline missense variants in the
and
genes, often referred to as variants of uncertain significance (VUS), have not been established. In this study, ...associations between 19 BRCA1 and 33 BRCA2 missense substitution variants and breast cancer risk were investigated through a breast cancer case-control study using genotyping data from 38 studies of predominantly European ancestry (41,890 cases and 41,607 controls) and nine studies of Asian ancestry (6,269 cases and 6,624 controls). The BRCA2 c.9104A>C, p.Tyr3035Ser (OR = 2.52;
= 0.04), and BRCA1 c.5096G>A, p.Arg1699Gln (OR = 4.29;
= 0.009) variant were associated with moderately increased risks of breast cancer among Europeans, whereas BRCA2 c.7522G>A, p.Gly2508Ser (OR = 2.68;
= 0.004), and c.8187G>T, p.Lys2729Asn (OR = 1.4;
= 0.004) were associated with moderate and low risks of breast cancer among Asians. Functional characterization of the BRCA2 variants using four quantitative assays showed reduced BRCA2 activity for p.Tyr3035Ser compared with wild-type. Overall, our results show how BRCA2 missense variants that influence protein function can confer clinically relevant, moderately increased risks of breast cancer, with potential implications for risk management guidelines in women with these specific variants.
.
Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. ...We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases) BRCA1 and 8,211 (631 ovarian cancer cases) BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA 2 mutation carriers respectively, within a retrospective cohort analytical framework. In BRCA1 mutation carriers one set of eight correlated candidate causal variants for ovarian cancer risk modification was identified (top SNP rs10124837, HR: 0.73, 95%CI: 0.68 to 0.79, p-value 2× 10-16). These variants were located up to 20 kb upstream of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95%CI: 0.59 to 0.80, p-value 1.0 × 10-6). The candidate causal in BRCA1 mutation carriers did not include the strongest associated variant at this locus in the general population. In sum, we identified a set of candidate causal variants in a region that encompasses the BNC2 transcription start site. The ovarian cancer association at 9p22.2 may be mediated by different variants in BRCA1 mutation carriers and in the general population. Thus, potentially different mechanisms may underlie ovarian cancer risk for mutation carriers and the general population.
Genetic linkage studies have provided evidence for a late-onset Alzheimer's disease (AD) susceptibility locus on chromosome 21q. We have tested, in a two-stage association study, whether allelic or ...haplotype variation of the beta-amyloid cleaving enzyme-2 (
BACE2) locus on chromosome 21q affects the risk of late-onset AD. In stage-1, an unselected population-based sample of Finns aged 85 years or over (
n
=
515) was analysed. Neuropathologic examination including beta-amyloid load quantification was possible in over 50% (
n
=
264) of these subjects. AD patients (
n
=
100) and controls (
n
=
48) were defined by modified neuropathological NIA-RI criteria. Positive associations were taken as a hypothesis, and tested in stage-2 using 483 AD families from the USA. Four single nucleotide polymorphisms (SNPs) of BACE2 gene were tested in stage-1. A SNP close to exon-6 was associated with neuropathologically verified AD (
p
=
0.02) and also with beta-amyloid load in non-selected autopsied subjects after conditioning with
APOE genotype (
p
=
0.001). In haplotype analysis a specific, relatively common haplotype (H5) was found to associate with AD (
p
=
0.004) and a second haplotype (H7) showed a weaker association with protection against AD (
p
=
0.04). In stage-2, the SNP association was not replicated, whereas the haplotype H5 association was replicated (
p
=
0.004) and a trend to association was found with the putative protective haplotype H7 (two-sided
p
=
0.08).
BACE2 haplotype association with AD in two independent datasets provides further evidence for an AD susceptibility locus on chromosome 21q within or close to
BACE2.
We and others have previously identified two distinct haplotypes of the
TAU gene in Caucasian populations. In this study, we have assessed whether these haplotypes show an association with ...Alzheimer's disease in a variety of populations. They do not. These data are consistent with the view that the involvement of TAU in Alzheimer's disease is a downstream event.
ApoE epsilon4 allele increases the risk of late-onset Alzheimer disease (AD) as well as the amount of beta-amyloid deposition in the brain. Because half of AD patients do not have ApoE epsilon4, it ...is important to search for other determinants of ApoE that modify AD risk. We tested whether the haplotype background of the most common ApoE allele, epsilon3, influences brain amyloid deposition or the risk of neuropathologically verified AD in a population-based sample of elderly Finns. To exclude the effects of ApoE protein polymorphism we focused these analyses on subjects homozygous for epsilon3. Haplotypes were defined using polymorphisms at positions - 491 and -219 of the ApoE promoter and at position +113 of intron-1. We found that epsilon3-haplotypes containing the promoter allele -219T were associated with reduced amyloid deposition and reduced risk of neuropathologically verified AD as compared to epsilon3-haplotypes containing -219G. The functional polymorphism(s) responsible for the haplotypic difference remains to be identified. These results indicate that there is significant allelic variation in the ApoE gene region, which modulates brain amyloid deposition and AD risk, independent of the ApoE protein polymorphism.
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