| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Barnes, DR, et al.
(author)
-
Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores
- 2022
-
In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 114:1, s. 109-122
-
Journal article (peer-reviewed)abstract
- BackgroundRecent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers.Methods483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)–negative (PRSER-), or ER-positive (PRSER+) breast cancer risk.ResultsPRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions.ConclusionsPopulation-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management.
|
|
| 5. |
- Aglietta, M, et al.
(author)
-
The cosmic ray primary composition between 10(15) and 10(16) eV from Extensive Air Showers electromagnetic and TeV muon data
- 2004
-
In: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 20:6, s. 641-652
-
Journal article (peer-reviewed)abstract
- The cosmic ray primary composition in the energy range between 10(15) and 10(16) eV, i.e., around the "knee" of the primary spectrum, has been studied through the combined measurements of the EAS-TOP air shower array (2005 m a. s.l., 10(5) m(2) collecting area) and the MACRO underground detector (963 m.a.s.l., 3100 m w.e. of minimum rock overburden, 920 m(2) effective area) at the National Gran Sasso Laboratories. The used observables are the air shower size (N-c) measured by EAS-TOP and the muon number (N-mu) recorded by MACRO. The two detectors are separated on average by 1200 m of rock, and located at a respective zenith angle of about 30degrees. The energy threshold at the surface for muons reaching the MACRO depth is approximately 1.3 TeV. Such muons are produced in the early stages of the shower development and in a kinematic region quite different from the one relevant for the usual N-mu - N-e studies. The measurement leads to a primary composition becoming heavier at the knee of the primary spectrum, the knee itself resulting from the steepening of the spectrum of a primary light component (p, He) of Deltay = 0.7 +/- 0.4 at E-0 similar to 4 x 10(15) eV. The result confirms the ones reported from the observation of the low energy muons at the surface (typically in the GeV energy range), showing that the conclusions do not depend on the production region kinematics. Thus, the hadronic interaction model used (CORSIKA/QGSJET) provides consistent composition results from data related to secondaries produced in a rapidity region exceeding the central one. Such an evolution of the composition in the knee region supports the "standard" galactic acceleration/propagation models that imply rigidity dependent breaks of the different components.. and therefore breaks occurring at lower energies in the spectra of the light nuclei. (C) 2003 Elsevier B.V. All rights reserved.
|
|
| 6. |
- Aglietta, M, et al.
(author)
-
The cosmic ray proton, helium and CNO fluxes in the 100 TeV energy region from TeV muons and EAS atmospheric Cherenkov light observations of MACRO and EAS-TOP
- 2004
-
In: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 21:3, s. 223-240
-
Journal article (peer-reviewed)abstract
- The primary cosmic ray (CR) proton, helium and CNO fluxes in the energy range 80-300 TeV are studied at the National Gran Sasso Laboratories by means of EAS-TOP (Campo Imperatore, 2005 m a.s.l.) and MACRO (deep underground, 3100 m w.e., the surface energy threshold for a muon reaching the detector being E-mu(th) approximate to 1.3 TeV). The measurement is based on: (a) the selection of primaries based on their energy/nucleon (i.e., with energy/nucleon sufficient to produce a muon with energy larger than 1.3 TeV) and the reconstruction of the shower geometry by means of the muons recorded by MACRO in the deep underground laboratories; (b) the detection of the associated atmospheric Cherenkov light (C.l.) signals by means of the C.l. detector of EAS-TOP. The C.l. density at core distance r > 100 m is directly related to the total primary energy E-0. Proton and helium ("p + He") and proton, helium and CNO ("p + He + CNO") primaries are thus selected at E-0 approximate to 80 TeV, and at E-0 similar or equal to 250 TeV, respectively. Their flux is measured: J(p+He)(80 TeV) = (1.8 +/- 0.4) x 10(-6) m(-1)-s(-1) sr(-1) TeV-1, and J(p+He+CNO)(250 TeV) = (1.1 +/- 0.3) x 10(-7) m(-2)-s(-1) sr(-1) TeV-1, their relative weights being J(p+He)(J(p+He+CNO)) over bar (250 TeV) = 0.78 +/- 0.17. By using the measurements of the proton spectrum obtained from the direct experiments and hadron flux data in the atmosphere, we obtain for the relative weights of the three components at 250 TeV: J(p) : J(He) : J(CNO) = (0.20 +/- 0.08) : (0.58 +/- 0.19) : (0.22 +/- 0.17). This corresponds to the dominance of helium over proton primaries at 100-1000 TeV, and a possible non-negligible contribution from CNO. The lateral distribution of Cherenkov light in Extensive Air Showers (EASs), which is related to the rate of energy deposit of the primary in the atmosphere, is measured for a selected proton and helium primary beam, and good agreement is found when compared with the one calculated with the CORSIKA/QGSJET simulation model. (C) 2004 Elsevier B.V. All rights reserved.
|
|
| 7. |
- Peterlongo, Paolo, et al.
(author)
-
FANCM c.5791C>T nonsense mutation (rs144567652) induces exon skipping, affects DNA repair activity and is a familial breast cancer risk factor.
- 2015
-
In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:18, s. 5345-5355
-
Journal article (peer-reviewed)abstract
- Numerous genetic factors that influence breast cancer risk are known. However, approximately two-thirds of the overall familial risk remain unexplained. To determine whether some of the missing heritability is due to rare variants conferring high to moderate risk, we tested for an association between the c.5791C>T nonsense mutation (p.Arg1931*; rs144567652) in exon 22 of FANCM gene and breast cancer. An analysis of genotyping data from 8635 familial breast cancer cases and 6625 controls from different countries yielded an association between the c.5791C>T mutation and breast cancer risk [odds ratio (OR) = 3.93 (95% confidence interval (CI) = 1.28-12.11; P = 0.017)]. Moreover, we performed two meta-analyses of studies from countries with carriers in both cases and controls and of all available data. These analyses showed breast cancer associations with OR = 3.67 (95% CI = 1.04-12.87; P = 0.043) and OR = 3.33 (95% CI = 1.09-13.62; P = 0.032), respectively. Based on information theory-based prediction, we established that the mutation caused an out-of-frame deletion of exon 22, due to the creation of a binding site for the pre-mRNA processing protein hnRNP A1. Furthermore, genetic complementation analyses showed that the mutation influenced the DNA repair activity of the FANCM protein. In summary, we provide evidence for the first time showing that the common p.Arg1931* loss-of-function variant in FANCM is a risk factor for familial breast cancer.
|
|
