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- Barnes, DR, et al.
(författare)
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Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores
- 2022
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 114:1, s. 109-122
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Tidskriftsartikel (refereegranskat)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.
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- Mavaddat, N, et al.
(författare)
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Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers
- 2020
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Ingår i: Breast cancer research : BCR. - : Springer Science and Business Media LLC. - 1465-542X. ; 22:1, s. 8-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe effect of risk-reducing salpingo-oophorectomy (RRSO) on breast cancer risk forBRCA1andBRCA2mutation carriers is uncertain. Retrospective analyses have suggested a protective effect but may be substantially biased. Prospective studies have had limited power, particularly forBRCA2mutation carriers. Further, previous studies have not considered the effect of RRSO in the context of natural menopause.MethodsA multi-centre prospective cohort of 2272BRCA1and 1605BRCA2mutation carriers was followed for a mean of 5.4 and 4.9 years, respectively; 426 women developed incident breast cancer. RRSO was modelled as a time-dependent covariate in Cox regression, and its effect assessed in premenopausal and postmenopausal women.ResultsThere was no association between RRSO and breast cancer forBRCA1(HR = 1.23; 95% CI 0.94–1.61) orBRCA2(HR = 0.88; 95% CI 0.62–1.24) mutation carriers. ForBRCA2mutation carriers, HRs were 0.68 (95% CI 0.40–1.15) and 1.07 (95% CI 0.69–1.64) for RRSO carried out before or after age 45 years, respectively. The HR forBRCA2mutation carriers decreased with increasing time since RRSO (HR = 0.51; 95% CI 0.26–0.99 for 5 years or longer after RRSO). Estimates for premenopausal women were similar.ConclusionWe found no evidence that RRSO reduces breast cancer risk forBRCA1mutation carriers. A potentially beneficial effect forBRCA2mutation carriers was observed, particularly after 5 years following RRSO. These results may inform counselling and management of carriers with respect to RRSO.
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- Takano, Yohei, et al.
(författare)
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Simulations of ocean deoxygenation in the historical era : insights from forced and coupled models
- 2023
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Ingår i: Frontiers in Marine Science. - 2296-7745. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Ocean deoxygenation due to anthropogenic warming represents a major threat to marine ecosystems and fisheries. Challenges remain in simulating the modern observed changes in the dissolved oxygen (O2). Here, we present an analysis of upper ocean (0-700m) deoxygenation in recent decades from a suite of the Coupled Model Intercomparison Project phase 6 (CMIP6) ocean biogeochemical simulations. The physics and biogeochemical simulations include both ocean-only (the Ocean Model Intercomparison Project Phase 1 and 2, OMIP1 and OMIP2) and coupled Earth system (CMIP6 Historical) configurations. We examine simulated changes in the O2 inventory and ocean heat content (OHC) over the past 5 decades across models. The models simulate spatially divergent evolution of O2 trends over the past 5 decades. The trend (multi-model mean and spread) for upper ocean global O2 inventory for each of the MIP simulations over the past 5 decades is 0.03 ± 0.39×1014 [mol/decade] for OMIP1, −0.37 ± 0.15×1014 [mol/decade] for OMIP2, and −1.06 ± 0.68×1014 [mol/decade] for CMIP6 Historical, respectively. The trend in the upper ocean global O2 inventory for the latest observations based on the World Ocean Database 2018 is −0.98×1014 [mol/decade], in line with the CMIP6 Historical multi-model mean, though this recent observations-based trend estimate is weaker than previously reported trends. A comparison across ocean-only simulations from OMIP1 and OMIP2 suggests that differences in atmospheric forcing such as surface wind explain the simulated divergence across configurations in O2 inventory changes. Additionally, a comparison of coupled model simulations from the CMIP6 Historical configuration indicates that differences in background mean states due to differences in spin-up duration and equilibrium states result in substantial differences in the climate change response of O2. Finally, we discuss gaps and uncertainties in both ocean biogeochemical simulations and observations and explore possible future coordinated ocean biogeochemistry simulations to fill in gaps and unravel the mechanisms controlling the O2 changes.
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