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- Escala-Garcia, Maria, et al.
(author)
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A network analysis to identify mediators of germline-driven differences in breast cancer prognosis
- 2020
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In: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 11:1
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Journal article (peer-reviewed)abstract
- Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies similar to 7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis.
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- Blomqvist, Niklas, 1987-
(author)
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Essays on Labor Economics : The Role of Government in Labor Supply Choices
- 2020
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Doctoral thesis (other academic/artistic)abstract
- "Right to Work Full-time" Policies and Involuntary Part-time EmploymentThis paper investigates the effect of right to full-time policies implemented to decrease involuntary part-time work for public care workers employed by Swedish municipalities. Taking advantage of a staggered decision process, these policies are evaluated using a difference-in-differences approach. Results show that involuntary part-time employment is real and significant, with 10% of part-time employed workers choosing full-time when given the opportunity. The effect mainly comes from a decrease in contracts of <75% of full-time and an increase in contracts of 80% of full-time and above. Further results from the full-time policies show that being more flexible in the choice of hours worked is popular among workers, indicated by an increase in tenure and reduced turnover in municipalities that offer more flexibility in the choice of hours worked.Hours Constraints and Tax Elasticity Estimates - Evidence from Swedish Public Care WorkersThere is a concern that tax elasticity estimates may be downward biased in the presence of optimization frictions for workers. So far, there is limited evidence on the nature of these optimization frictions. This paper provides new insight into one part of the optimization frictions black box, namely hours constraints. Using unique and newly collected data, I exploit a staggered implementation of a policy that gave some public care workers the opportunity to choose their preferred hours of work. Taking advantage of this policy, I estimate differences in tax elasticities between constrained and unconstrained public care workers by comparing bunching at a large tax kink in the Swedish tax system. The empirical evidence points to the conclusion that hours constraints do not affect tax elasticity estimates.Restricting Residence Permits - Short-Run Evidence from a Swedish ReformIn June 2016, the Swedish parliament decided to restrict the granting of permanent residence permits for asylum seekers in Sweden. The new status quo for a refugee is a temporary rather than a permanent residence permit. In a first evaluation of this reform we use a Regression discontinuity analysis in which we follow refugees, aged 25-65, over their first years after arrival. Our main results show that a temporary residence permit increases the probability of working and enrolling in regular education.Mom and Dad Got Jobs: Natural Resources, Economic Activity, and Infant HealthThe impact of local economic shocks, such as the discovery and exploitation of natural resources, on labor markets and health is not well understood. Both positive and negative effects have been documented in the literature. In this paper, we show that the phase before active resource extraction begins directly affects the local economy. This implies that previous estimates – typically based on designs exploiting differences before and after the active phase of extraction begins - may have understated the actual effect of natural resource extraction on outcomes of interest. Using rich data from Sweden combined with differences in the timing and location of mineral exploitation permits, we find a positive impact on female and male employment and earnings and a negative effect on housing prices. Children’s health outcomes are also negatively affected, an effect likely driven by the increase in local economic activity rather than extraction-related externalities.
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| 6. |
- Yang, Xin, et al.
(author)
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Cancer risks associated with germline PALB2 pathogenic variants : An international study of 524 families
- 2020
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In: Journal of Clinical Oncology. - 0732-183X. ; 38:7, s. 674-685
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Journal article (peer-reviewed)abstract
- PURPOSE To estimate age-specific relative and absolute cancer risks of breast cancer and to estimate risks of ovarian, pancreatic, male breast, prostate, and colorectal cancers associated with germline PALB2 pathogenic variants (PVs) because these risks have not been extensively characterized. METHODS We analyzed data from 524 families with PALB2 PVs from 21 countries. Complex segregation analysis was used to estimate relative risks (RRs; relative to country-specific population incidences) and absolute risks of cancers. The models allowed for residual familial aggregation of breast and ovarian cancer and were adjusted for the family-specific ascertainment schemes. RESULTS We found associations between PALB2 PVs and risk of female breast cancer (RR, 7.18; 95% CI, 5.82 to 8.85; P = 6.5 × 10-76), ovarian cancer (RR, 2.91; 95% CI, 1.40 to 6.04; P = 4.1 × 10-3), pancreatic cancer (RR, 2.37; 95% CI, 1.24 to 4.50; P = 8.7 × 10-3), and male breast cancer (RR, 7.34; 95% CI, 1.28 to 42.18; P = 2.6 3 1022). There was no evidence for increased risks of prostate or colorectal cancer. The breast cancer RRs declined with age (P for trend = 2.0 × 10-3). After adjusting for family ascertainment, breast cancer risk estimates on the basis of multiple case families were similar to the estimates from families ascertained through population-based studies (P for difference = .41). On the basis of the combined data, the estimated risks to age 80 years were 53% (95% CI, 44% to 63%) for female breast cancer, 5% (95% CI, 2% to 10%) for ovarian cancer, 2%-3% (95% CI females, 1% to 4%; 95% CI males, 2% to 5%) for pancreatic cancer, and 1% (95% CI, 0.2% to 5%) for male breast cancer. CONCLUSION These results confirm PALB2 as a major breast cancer susceptibility gene and establish substantial associations between germline PALB2 PVs and ovarian, pancreatic, and male breast cancers. These findings will facilitate incorporation of PALB2 into risk prediction models and optimize the clinical cancer risk management of PALB2 PV carriers.
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