| 1. |
|
|
| 2. |
|
|
| 3. |
- Figlioli, G, et al.
(författare)
-
FANCM missense variants and breast cancer risk: a case-control association study of 75,156 European women
- 2023
-
Ingår i: European journal of human genetics : EJHG. - : Springer Science and Business Media LLC. - 1476-5438 .- 1018-4813. ; 31:5, s. 578-587
-
Tidskriftsartikel (refereegranskat)abstract
- Evidence from literature, including the BRIDGES study, indicates that germline protein truncating variants (PTVs) in FANCM confer moderately increased risk of ER-negative and triple-negative breast cancer (TNBC), especially for women with a family history of the disease. Association between FANCM missense variants (MVs) and breast cancer risk has been postulated. In this study, we further used the BRIDGES study to test 689 FANCM MVs for association with breast cancer risk, overall and in ER-negative and TNBC subtypes, in 39,885 cases (7566 selected for family history) and 35,271 controls of European ancestry. Sixteen common MVs were tested individually; the remaining rare 673 MVs were tested by burden analyses considering their position and pathogenicity score. We also conducted a meta-analysis of our results and those from published studies. We did not find evidence for association for any of the 16 variants individually tested. The rare MVs were significantly associated with increased risk of ER-negative breast cancer by burden analysis comparing familial cases to controls (OR = 1.48; 95% CI 1.07–2.04; P = 0.017). Higher ORs were found for the subgroup of MVs located in functional domains or predicted to be pathogenic. The meta-analysis indicated that FANCM MVs overall are associated with breast cancer risk (OR = 1.22; 95% CI 1.08–1.38; P = 0.002). Our results support the definition from previous analyses of FANCM as a moderate-risk breast cancer gene and provide evidence that FANCM MVs could be low/moderate risk factors for ER-negative and TNBC subtypes. Further genetic and functional analyses are necessary to clarify better the increased risks due to FANCM MVs.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Turunen, S, et al.
(författare)
-
The Increased Trend of Medical Treatment for Thyroid Diseases during Pregnancy: A 13-Year National Study
- 2021
-
Ingår i: European thyroid journal. - : Bioscientifica. - 2235-0640 .- 2235-0802. ; 10:3, s. 230-236
-
Tidskriftsartikel (refereegranskat)abstract
- <b><i>Objective:</i></b> Thyroid dysfunction affects up to 5–7% of all pregnancies. The rates of thyroid hormone use in nonpregnant population have substantially increased in recent years. The aim of this study was to assess possible changes in the use of levothyroxine substitution and antithyroid drugs over time in pregnant women. <b><i>Methods:</i></b> The study data consisted of all singleton pregnancies (<i>N</i> = 736,873) between 2004 and 2016 in Finland collected from the Finnish Medical Birth Register. The Prescription Register and Special Refund Entitlement Register provided information on levothyroxine and antithyroid drug purchases. The annual rates of levothyroxine and antithyroid drug prescription redemptions were explored to estimate changes in exposure rates to thyroid medication from 2004 to 2016. Joinpoint regression analyses were performed to explore interannual variability in levothyroxine and antithyroid drug treatment. <b><i>Results:</i></b> There was more than a five-fold increase in levothyroxine use during the study period; in 2004, 1.1% of pregnant women had levothyroxine treatment, and by 2016, the prevalence increased to 6.2%. In addition, we observed a slight increase in antithyroid medication during pregnancy, but antithyroid drug use during pregnancy overall was very rare. In 2004, 0.05% of pregnant women used antithyroid drugs, and by 2016, this percentage had increased to 0.14%. <b><i>Conclusions:</i></b> Our study shows that the rate of levothyroxine use in pregnancy has markedly increased. This suggests that tracing and screening relevant patients and awareness of thyroid disorders on pregnancy and their significance for the pregnancy outcome have increased and the threshold to treat thyroid disorders has declined.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
- Mantere, Tuomo, et al.
(författare)
-
Case-control analysis of truncating mutations in DNA damage response genes connects TEX15 and FANCD2 with hereditary breast cancer susceptibility
- 2017
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1
-
Tidskriftsartikel (refereegranskat)abstract
- Several known breast cancer susceptibility genes encode proteins involved in DNA damage response (DDR) and are characterized by rare loss-of-function mutations. However, these explain less than half of the familial cases. To identify novel susceptibility factors, 39 rare truncating mutations, identified in 189 Northern Finnish hereditary breast cancer patients in parallel sequencing of 796 DDR genes, were studied for disease association. Mutation screening was performed for Northern Finnish breast cancer cases (n = 578-1565) and controls (n = 337-1228). Mutations showing potential cancer association were analyzed in additional Finnish cohorts. c.7253dupT in TEX15, encoding a DDR factor important in meiosis, associated with hereditary breast cancer (p = 0.018) and likely represents a Northern Finnish founder mutation. A deleterious c.2715 + 1G > A mutation in the Fanconi anemia gene, FANCD2, was over two times more common in the combined Finnish hereditary cohort compared to controls. A deletion (c.640-644del5) in RNF168, causative for recessive RIDDLE syndrome, had high prevalence in majority of the analyzed cohorts, but did not associate with breast cancer. In conclusion, truncating variants in TEX15 and FANCD2 are potential breast cancer risk factors, warranting further investigations in other populations. Furthermore, high frequency of RNF168 c.640-644del5 indicates the need for its testing in Finnish patients with RIDDLE syndrome symptoms.
|
|
| 14. |
|
|
| 15. |
- Purdue-Smithe, AC, et al.
(författare)
-
The Joint Role of Thyroid Function and Iodine Status on Risk of Preterm Birth and Small for Gestational Age: A Population-Based Nested Case-Control Study of Finnish Women
- 2019
-
Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 11:11
-
Tidskriftsartikel (refereegranskat)abstract
- Normal maternal thyroid function during pregnancy is essential for fetal development and depends upon an adequate supply of iodine. Little is known about how iodine status is associated with preterm birth and small for gestational age (SGA) in mildly iodine insufficient populations. Our objective was to evaluate associations of early pregnancy serum iodine, thyroglobulin (Tg), and thyroid-stimulating hormone (TSH) with odds of preterm birth and SGA in a prospective, population-based, nested case-control study from all births in Finland (2012–2013). Cases of preterm birth (n = 208) and SGA (n = 209) were randomly chosen from among all singleton births. Controls were randomly chosen from among singleton births that were not preterm (n = 242) or SGA (n = 241) infants during the same time period. Women provided blood samples at 10–14 weeks’ gestation for serum iodide, Tg and TSH measurement. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for preterm birth and SGA. Each log-unit increase in serum iodide was associated with higher odds of preterm birth (adjusted OR = 1.19, 95% CI = 1.02–1.40), but was not associated with SGA (adjusted OR = 1.01, 95% CI = 0.86–1.18). Tg was not associated with preterm birth (OR per 1 log-unit increase = 0.87, 95% CI = 0.73–1.05), but was inversely associated with SGA (OR per log-unit increase = 0.78, 95% CI = 0.65–0.94). Neither high nor low TSH (versus normal) were associated with either outcome. These findings suggest that among Finnish women, iodine status is not related to SGA, but higher serum iodide may be positively associated with preterm birth.
|
|
| 16. |
|
|
| 17. |
- Scheel, Marieke, et al.
(författare)
-
Increased Central European forest mortality explained by higher harvest rates driven by enhanced productivity
- 2022
-
Ingår i: Environmental Research Letters. - : IOP Publishing. - 1748-9318 .- 1748-9326. ; 17:11
-
Tidskriftsartikel (refereegranskat)abstract
- Increasing tree growth and mortality rates in Europe are still poorly understood and have been attributed to a variety of drivers. This study explored the role of climate drivers, management and age structure in driving changes in tree mortality rates in six Central European countries from 1985 to 2010, using the process-based vegetation model LPJ-GUESS. Simulations show a strong positive trend in canopy mortality rates in Central Europe, consistent with satellite observations. This trend was explained by an assumed increase in managed thinning in response to a modelled increase in forest productivity caused by climate change and rising atmospheric CO2 concentration. Simulated rates of canopy mortality were highly sensitive to the minimum tree size threshold applied for inclusion in the rate calculation, agreeing with satellite observations that are likely to only capture the loss of relatively large trees. The calculated trends in mortality rate also differed substantially depending on the metric used (i.e. carbon, stem or canopy mortality), highlighting the challenge of comparing tree mortality trends from different observation types. We conclude that changes in forest productivity and management in combination can profoundly affect regional-scale patterns of tree mortality. Our findings underscore the fact that increasing forest mortality can occur without reductions in forest growth when mediated by management responses to increasing productivity.
|
|
