| 1. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Hollestelle, Antoinette, et al.
(författare)
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No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
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Tidskriftsartikel (refereegranskat)abstract
- Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
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| 3. |
- Wang, Zhaoming, et al.
(författare)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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| 4. |
- Asker, Martin, et al.
(författare)
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Risk factors for, and prevention of, shoulder injuries in overhead sports : a systematic review with best-evidence synthesis.
- 2018
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Ingår i: British Journal of Sports Medicine. - : BMJ. - 0306-3674 .- 1473-0480. ; 52:20, s. 312-1319
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Forskningsöversikt (refereegranskat)abstract
- OBJECTIVE: To assess the evidence for risk factors and prevention measures for shoulder injuries in overhead sports.DESIGN: Systematic review with best-evidence synthesis.DATA SOURCES: Medline (Ovid), PubMed (complementary search), Embase (Elsevier), Cochrane (Wiley), SPORTDiscus (Ebsco) and Web of Science Core Collection (Thomson Reuters), from 1 January 1990 to 15 May 2017.ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials, cohort studies and case-control studies on risk factors or prevention measures for shoulder injuries in overhead sports. The eligible studies were quality assessed using the Scottish Intercollegiate Guidelines Network criteria.RESULTS: Of 4778 studies identified, 38 were eligible for quality review and 17 met the quality criteria to be included in the evidence synthesis. One additional quality study presented a shoulder injury prevention programme. Most studies focused on baseball, lacrosse or volleyball (n=13). The risk factors examined included participation level (competition vs training) (n=10), sex (n=4), biomechanics (n=2) and external workload (n=2). The evidence for all risk factors was limited or conflicting. The effect of the prevention programme within the subgroup of uninjured players at baseline was modest and possibly lacked statistical power.CONCLUSIONS: All investigated potential risk factors for shoulder injury in overhead sports had limited evidence, and most were non-modifiable (eg, sex). There is also limited evidence for the effect of shoulder injury prevention measures in overhead sports.PROSPERO TRIAL REGISTRATION NUMBER: CRD42015026850.
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| 5. |
- Barbulescu, Andrei, et al.
(författare)
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Oral metronidazole use and risk of acute pancreatitis : a population-based case-control study.
- 2018
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Ingår i: Clinical Epidemiology. - 1179-1349. ; 10, s. 1573-1581
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Oral metronidazole used in combined regimens for Helicobacter pylori eradication has been associated with an increased risk of acute pancreatitis; however, it is less clear whether a similar association exists for single-regimen metronidazole. We, therefore, examined the association of single and combined regimens of oral metronidazole with risk of acute pancreatitis.METHODS: In this population-based case-control study, all individuals in Sweden (aged 40-84 years) hospitalized with acute pancreatitis between January 2006 and December 2008 were identified from a national hospital register (n=5,996). Controls, matched for calendar year, age, and sex, were randomly sampled from a national population register (n=60,681). Data on oral metronidazole and covariates were extracted from national health and prescription registers. Odds ratios (ORs) of acute pancreatitis, according to timing of the latest metronidazole prescription before hospitalization, were estimated using logistic regression models. Confounding by indication was examined by contrasting the main results with the association when amoxicillin was used as exposure. The robustness of results was examined by calculating incidence rate ratios using a self-controlled case series approach.RESULTS: After adjustment for potential confounders, there was a substantially increased risk of acute pancreatitis within 30 days of oral metronidazole exposure, both for single (OR: 4.06; 95% confidence interval [CI]: 1.90-8.64) and combined (OR: 11.80; 95% CI: 6.86-20.28) regimens, compared to nonexposure. In contrast, the adjusted OR was 1.79 (95% CI: 1.25-2.54) for current use of amoxicillin compared to nonexposure. These results were supported by the self-controlled cases series analysis (incidence rate ratio: 3.30; 95% CI: 2.69-4.06, for single and combined regimens of oral metronidazole pooled). There was no strong association between oral metronidazole and acute pancreatitis more than 30 days after exposure.CONCLUSION: There was an increased risk of acute pancreatitis within 30 days of exposure to single and combined regimens of oral metronidazole. While reverse causality and confounding by indication cannot be entirely excluded, they are unlikely to fully explain the association. These results warrant an increased awareness among physicians.
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| 6. |
- Brooke, Hannah L, et al.
(författare)
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A systematic literature review with meta-analyses of within- and between-day differences in objectively measured physical activity in school-aged children.
- 2014
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Ingår i: Sports Medicine. - : Springer Science and Business Media LLC. - 0112-1642 .- 1179-2035. ; 44:10, s. 1427-38
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Targeting specific time periods of the day or week may enhance physical activity (PA) interventions in youth. The most prudent time segments to target are currently unclear.OBJECTIVES: To systematically review the literature describing differences in young people's objectively measured PA on weekdays vs. weekends, in school vs. out of school, weekends vs. out of school and lesson time vs. break time.METHODS: Electronic databases were searched for English-language, cross-sectional studies of school-aged children (4-18 years) reporting time-segment-specific accelerometer-measured PA from 01/1990 to 01/2013. We meta-analysed standardised mean differences (SMD) between time segments for mean accelerometer counts per minute (TPA) and minutes in moderate-to-vigorous PA (MVPA). SMD is reported in units of standard deviation; 0.2, 0.5 and 0.8 represent small, moderate and large effects. Heterogeneity was explored using meta-regression (potential effect modifiers: age, sex and study setting).RESULTS: Of the 54 included studies, 37 were eligible for meta-analyses. Children were more active on weekdays than weekends [pooled SMD (95 % CI) TPA 0.14 (0.08; 0.20), MVPA 0.42 (0.35; 0.49)]. On school days, TPA was lower in school than out of school; however, marginally more MVPA was accumulated in school [TPA -0.24 (-0.40; -0.08), MVPA 0.17 (-0.03; 0.38)]. TPA was slightly lower on weekends than out of school on school days, but a greater absolute volume of MVPA was performed on weekends [TPA -0.10 (-0.19; -0.01), MVPA 1.02 (0.82; 1.23)]. Heterogeneity between studies was high (I (2) 73.3-96.3 %), with 20.3-53.1 % of variance between studies attributable to potential moderating factors.CONCLUSIONS: School-aged children are more active on weekdays than weekend days. The outcome measure influences the conclusions for other comparisons. Findings support the tailoring of intervention strategies to specific time periods.
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| 7. |
- Brooke, Hannah L, et al.
(författare)
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Adult children's socioeconomic resources and mothers' survival after a breast cancer diagnosis : a Swedish population-based cohort study.
- 2017
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 7:3
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Socioeconomic inequalities in survival after breast cancer persist worldwide. We aim to determine whether adult offspring's socioeconomic resources contribute to inequalities in mothers' survival after breast cancer.METHODS: 14 231 women, aged 65-79 years, with a child aged ≥30 years and a first primary diagnosis of breast cancer in the National Cancer Register between 2001 and 2010 were followed until death, 10 years after diagnosis, or end of study (December 2015). Relative survival proportions and excess mortality within 10 years of diagnosis by strata of offspring's education level and disposable income were estimated using flexible parametric models accounting for measures of mothers' socioeconomic position and expected mortality in the general population.RESULTS: 4292 women died during 102 236 person-years of follow-up. Crude 10-year relative survival proportions for mothers of children with >14, 12-14 and <12 years of education were 0.89 (0.87 to 0.91), 0.87 (0.85 to 0.89) and 0.79 (0.76 to 0.81), respectively. Compared with mothers of children with >14 years of education, mothers of children with <12 or 12-14 years of education had substantially higher excess mortality (excess HR 1.69 (1.38 to 2.07) and 1.22 (1.00 to 1.48), respectively). Higher mortality did not differ between tertiles of offspring's disposable income.CONCLUSIONS: Adult offspring's education level may contribute to inequalities in mothers' survival after breast cancer. Clinicians should be aware of the educational context beyond the individual and women with less educated offsprings may require extra support. This should be considered in future research, policy frameworks and interventions aimed at reducing survival inequalities.
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| 8. |
- Brooke, Hannah L, et al.
(författare)
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Changes in time-segment specific physical activity between ages 10 and 14 years : A longitudinal observational study.
- 2016
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Ingår i: Journal of Science and Medicine in Sport. - : Elsevier BV. - 1440-2440 .- 1878-1861. ; 19:1, s. 29-34
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Describe (1) time-segment specific changes in physical activity (PA) into adolescence, (2) differences in change in PA between specific time-segments (weekdays-weekends, in-school-out-of-school, out-of-school-weekends, lesson-time-lunch-time), and (3) associations of change in time-segment specific with overall PA.DESIGN: Longitudinal observational study (4-year follow-up).METHODS: Children from the SPEEDY study (n=769, 42% boys) had PA measured by accelerometer for at least three days at ages 10.2±0.3, 11.2±0.3 and 14.3±0.3years. Changes in moderate-to-vigorous PA (ΔMVPA, minutes ≥2000counts/minute [cpm]) and total PA (ΔTPA, average cpm) during weekdays, weekends, in-school, out-of-school, lesson-times and lunch-times, were tested using three level (age, individual, school) mixed-effects linear regression. Differences in ΔMVPA/ΔTPA between time-segments were tested using time-segment×age interaction terms. Associations of four-year time-segment specific ΔMVPA/ΔTPA with four-year overall ΔMVPA/ΔTPA were tested using two level (time-segment specific ΔMVPA/ΔTPA, school) mixed-effects linear regression.RESULTS: MVPA and TPA declined in all time-segments, except lesson-time MVPA. Annual ΔMVPA and, for boys only, ΔTPA was greater on weekends than weekdays (beta±SE for interaction term: boys, -3.53±0.83min, -29.64±7.64cpm; girls, -2.20±0.64min) and out-of-school (boys, -4.36±0.79min, -19.36±8.46cpm; girls, -2.44±0.63min). ΔMVPA and ΔTPA during lunch-time was greater than during lesson-time (boys, -0.96±0.20min, -36.43±6.55cpm; girls, -0.90±0.13min, -38.72±4.40cpm). ΔTPA was greater out-of-school than in-school (boys, -19.89±6.71cpm; girls, -18.46±6.51cpm). For all time-segments, four-year ΔMVPA/ΔTPA was positively associated with four-year overall ΔMVPA/ΔTPA (all p<0.042), except for girl's in-school and lunch-time TPA.CONCLUSIONS: Interventions focused on PA maintenance could target all time-segments, but weekends and out-of-school may be particularly advantageous due to the relatively large declines observed.
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| 9. |
- Brooke, Hannah L, et al.
(författare)
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Frequency and duration of physical activity bouts in school-aged children : A comparison within and between days.
- 2016
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Ingår i: Preventive medicine reports. - : Elsevier BV. - 2211-3355. ; 4, s. 585-590
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Tidskriftsartikel (refereegranskat)abstract
- Understanding how physical activity (PA) patterns vary within and between days may guide PA promotion in young people. We aimed to 1) describe and compare the frequency (bouts/day) and duration (min/bout) of bouts of moderate-to-vigorous intensity PA (MVPA) on weekdays vs. weekends and in-school vs. out-of-school, and 2) assess associations of bout frequency and duration in these time-segments with overall PA. We used cross-sectional accelerometer data from 2737 children (aged 6-19 years) in the United States National Health and Nutrition Examination Survey (NHANES) 2003-2006. A bout was defined as MVPA (≥ 2000 counts per minute [cpm]) lasting ≥ 3 min. Adjusted Wald tests were used to assess differences in bout characteristics between time-segments. Linear regression was used to examine the association of time-segment specific bout characteristics with daily minutes of MVPA and PA volume (average cpm). Bout frequency was higher on weekdays than weekends (median [IQR] 4.3 [2.2-7.2] vs. 3.0 [1.0-6.5] bouts/day, p < 0.001); however, bout duration did not differ (4.7 [4.0-5.7] vs. 4.5 [3.7-5.8] min/bout, p = 0.33). More bouts were accumulated out-of-school compared with in-school (2.2 [1.0-4.0] vs. 1.8 [0.8-3.2] bouts/day, p < 0.001), but bout duration was similar (4.7 [3.8-5.8] vs. 4.5 [3.8-5.7] min/bout, p = 0.158). For all time-segments, the frequency and duration of bouts of MVPA were independently and positively associated with overall MVPA and PA volume. In conclusion, the characteristics of children's PA vary within and between days; accounting for this in intervention design may improve future interventions. However, increasing bout frequency or duration in any time-segment may be beneficial for overall PA.
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| 10. |
- Brooke, Hannah L, et al.
(författare)
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Methodological choices affect cancer incidence rates : a cohort study.
- 2017
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Ingår i: Population Health Metrics. - : Springer Science and Business Media LLC. - 1478-7954. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Incidence rates are fundamental to epidemiology, but their magnitude and interpretation depend on methodological choices. We aimed to examine the extent to which the definition of the study population affects cancer incidence rates.METHODS: All primary cancer diagnoses in Sweden between 1958 and 2010 were identified from the national Cancer Register. Age-standardized and age-specific incidence rates of 29 cancer subtypes between 2000 and 2010 were calculated using four definitions of the study population: persons resident in Sweden 1) based on general population statistics; 2) with no previous subtype-specific cancer diagnosis; 3) with no previous cancer diagnosis except non-melanoma skin cancer; and 4) with no previous cancer diagnosis of any type. We calculated absolute and relative differences between methods.RESULTS: Age-standardized incidence rates calculated using general population statistics ranged from 6% lower (prostate cancer, incidence rate difference: -13.5/100,000 person-years) to 8% higher (breast cancer in women, incidence rate difference: 10.5/100,000 person-years) than incidence rates based on individuals with no previous subtype-specific cancer diagnosis. Age-standardized incidence rates in persons with no previous cancer of any type were up to 10% lower (bladder cancer in women) than rates in those with no previous subtype-specific cancer diagnosis; however, absolute differences were <5/100,000 person-years for all cancer subtypes.CONCLUSIONS: For some cancer subtypes incidence rates vary depending on the definition of the study population. For these subtypes, standardized incidence ratios calculated using general population statistics could be misleading. Moreover, etiological arguments should be used to inform methodological choices during study design.
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