| 181. |
- Carreras-Torres, Robert, et al.
(författare)
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The causal relevance of body mass index in different histological types of lung cancer : a Mendelian randomization study
- 2016
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Body mass index (BMI) is inversely associated with lung cancer risk in observational studies, even though it increases the risk of several other cancers, which could indicate confounding by tobacco smoking or reverse causality. We used the two-sample Mendelian randomization (MR) approach to circumvent these limitations of observational epidemiology by constructing a genetic instrument for BMI, based on results from the GIANT consortium, which was evaluated in relation to lung cancer risk using GWAS results on 16,572 lung cancer cases and 21,480 controls. Results were stratified by histological subtype, smoking status and sex. An increase of one standard deviation (SD) in BMI (4.65 Kg/m(2)) raised the risk for lung cancer overall (OR = 1.13; P = 0.10). This was driven by associations with squamous cell (SQ) carcinoma (OR = 1.45; P = 1.2 × 10(-3)) and small cell (SC) carcinoma (OR = 1.81; P = 0.01). An inverse trend was seen for adenocarcinoma (AD) (OR = 0.82; P = 0.06). In stratified analyses, a 1 SD increase in BMI was inversely associated with overall lung cancer in never smokers (OR = 0.50; P = 0.02). These results indicate that higher BMI may increase the risk of certain types of lung cancer, in particular SQ and SC carcinoma.
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| 182. |
- Cheng, Chao, et al.
(författare)
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Mosaic chromosomal alterations are associated with increased lung cancer risk : insight from the INTEGRAL-ILCCO cohort analysis
- 2023
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Ingår i: Journal of Thoracic Oncology. - : Elsevier. - 1556-0864 .- 1556-1380.
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Mosaic chromosomal alterations (mCAs) detected in white blood cells represent a type of clonal hematopoiesis (CH) that is understudied compared with CH-related somatic mutations. A few recent studies indicated their potential link with nonhematological cancers, especially lung cancer. Methods: In this study, we investigated the association between mCAs and lung cancer using the high-density genotyping data from the OncoArray study of INTEGRAL-ILCCO, the largest single genetic study of lung cancer with 18,221 lung cancer cases and 14,825 cancer-free controls. Results: We identified a comprehensive list of autosomal mCAs, ChrX mCAs, and mosaic ChrY (mChrY) losses from these samples. Autosomal mCAs were detected in 4.3% of subjects, in addition to ChrX mCAs in 3.6% of females and mChrY losses in 9.6% of males. Multivariable logistic regression analysis indicated that the presence of autosomal mCAs in white blood cells was associated with an increased lung cancer risk after adjusting for key confounding factors, including age, sex, smoking status, and race. This association was mainly driven by a specific type of mCAs: copy-neutral loss of heterozygosity on autosomal chromosomes. The association between autosome copy-neutral loss of heterozygosity and increased risk of lung cancer was further confirmed in two major histologic subtypes, lung adenocarcinoma and squamous cell carcinoma. In addition, we observed a significant increase of ChrX mCAs and mChrY losses in smokers compared with nonsmokers and racial differences in certain types of mCA events. Conclusions: Our study established a link between mCAs in white blood cells and increased risk of lung cancer.
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| 183. |
- Christensen, Torben, et al.
(författare)
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Element interactions and trace gas exchange
- 2003
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Ingår i: Interactions of the Major Biogeochemical Cycles: Global Change and Human Impacts. - 1559630663 - 1559630655 ; SCOPE 61, s. 247-258
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 184. |
- Dai, Juncheng, et al.
(författare)
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Genome-wide association study of INDELs identified four novel susceptibility loci associated with lung cancer risk
- 2020
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 146:10, s. 2855-2864
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified 45 susceptibility loci associated with lung ncer. Only less than SNPs, small insertions and deletions (INDELs) are the second most abundant netic polymorphisms in the human genome. INDELs are highly associated with multiple human seases, including lung cancer. However, limited studies with large-scale samples have been available to stematically evaluate the effects of INDELs on lung cancer risk. Here, we performed a large-scale meta- alysis to evaluate INDELs and their risk for lung cancer in 23,202 cases and 19,048 controls. Functional notations were performed to further explore the potential function of lung cancer risk INDELs. nditional analysis was used to clarify the relationship between INDELs and SNPs. Four new risk loci re identified in genome-wide INDEL analysis (1p13.2: rs5777156, Insertion, OR = 0.92, p = 9.10 x 10(- ; 4q28.2: rs58404727, Deletion, OR = 1.19, p = 5.25 x 10(-7); 12p13.31: rs71450133, Deletion, OR = 09, p = 8.83 x 10(-7); and 14q22.3: rs34057993, Deletion, OR = 0.90, p = 7.64 x 10(-8)). The eQTL alysis and functional annotation suggested that INDELs might affect lung cancer susceptibility by gulating the expression of target genes. After conducting conditional analysis on potential causal SNPs, e INDELs in the new loci were still nominally significant. Our findings indicate that INDELs could be tentially functional genetic variants for lung cancer risk. Further functional experiments are needed to tter understand INDEL mechanisms in carcinogenesis.
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| 185. |
- Davies, John R., et al.
(författare)
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An inherited variant in the gene coding for vitamin D-binding protein and survival from cutaneous melanoma: a BioGenoMEL study
- 2014
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Ingår i: Pigment Cell & Melanoma Research. - : Wiley. - 1755-148X .- 1755-1471. ; 27:2, s. 234-243
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Tidskriftsartikel (refereegranskat)abstract
- An association between low serum vitamin D levels and poorer melanoma survival has been reported. We have studied inheritance of a polymorphism of the GC gene, rs2282679, coding for the vitamin D-binding protein, which is associated with lower serum levels of vitamin D, in a meta-analysis of 3137 melanoma patients. The aim was to investigate evidence for a causal relationship between vitamin D and outcome (Mendelian randomization). The variant was not associated with reduced overall survival (OS) in the UK cohort, per-allele hazard ratio (HR) for death 1.23 (95% confidence interval (CI) 0.93, 1.64). In the smaller cohorts, HR in OS analysis was 1.07 (95% CI 0.88, 1.3) and for all cohorts combined, HR for OS was 1.09 (95% CI 0.93, 1.29). There was evidence of increased melanoma-specific deaths in the seven cohorts for which these data were available. The lack of unequivocal findings despite the large sample size illustrates the difficulties of implementing Mendelian randomization.
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| 186. |
- Dema, Emily, et al.
(författare)
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How did the COVID-19 pandemic affect access to condoms, chlamydia and HIV testing, and cervical cancer screening at a population level in Britain? (Natsal-COVID)
- 2023
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Ingår i: Sexually Transmitted Infections. - : BMJ Publishing Group Ltd. - 1368-4973 .- 1472-3263. ; 99:4, s. 261-267
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To investigate how differential access to key interventions to reduce STIs, HIV and their sequelae changed during the COVID-19 pandemic.Methods: British participants (18-59 years) completed a cross-sectional web survey 1 year (March-April 2021) after the initial lockdown in Britain. Quota-based sampling and weighting resulted in a quasi-representative population sample. We compared Natsal-COVID data with Natsal-3, a household-based probability sample cross-sectional survey (16-74 years) conducted in 2010-2012. Reported unmet need for condoms because of the pandemic and uptake of chlamydia testing/HIV testing/cervical cancer screening were analysed among sexually experienced participants (18-44 years) (n=3869, Natsal-COVID; n=8551, Natsal-3). ORs adjusted for age and other potential confounders describe associations with demographic and behavioural factors.Results: In 2021, 6.9% of women and 16.2% of men reported unmet need for condoms because of the pandemic. This was more likely among participants: aged 18-24 years, of black or black British ethnicity, and reporting same-sex sex (past 5 years) or one or more new relationships (past year). Chlamydia and HIV testing were more commonly reported by younger participants, those reporting condomless sex with new sexual partners and men reporting same-sex partners; a very similar distribution to 10 years previously (Natsal-3). However, there were differences during the pandemic, including stronger associations with chlamydia testing for men reporting same-sex partners; with HIV testing for women reporting new sexual partners and with cervical screening among smokers.Conclusions: Our study suggests differential access to key primary and secondary STI/HIV prevention interventions continued during the first year of the COVID-19 pandemic. However, there was not strong evidence that differential access has changed during the pandemic when compared with 2010-2012. While the pandemic might not have exacerbated inequalities in access to primary and secondary prevention, it is clear that large inequalities persisted, typically among those at greatest STI/HIV risk.
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| 187. |
- Dema, Emily, et al.
(författare)
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How did the COVID-19 pandemic affect unmet need for condoms at a population level? (Natsal-COVID)
- 2022
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Ingår i: Sexually Transmitted Infections. - : BMJ Publishing Group Ltd. - 1368-4973 .- 1472-3263. ; 98:Suppl. 1, s. A42-A42
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Use of condoms to prevent STIs/HIV and unplanned pregnancy remains important during the COVID-19 pandemic. However, it is unknown whether the pandemic affected condom access and which population groups were most impacted.Methods: 6658 participants (18-59y) completed a cross-sectional web survey one-year after the initial British lockdown from 23 March 2020. Quota-based sampling and weighting resulted in a sample that was quasi-representative of the British population. We report the prevalence of unmet need for condoms because of the pandemic among sexually-experienced participants aged 18-44 years (n=2869). Adjusted odds ratios (AOR) quantify associations with demographic and behavioural factors.Results: Overall, 6.9% of women and 16.2% of men reported unmet need for condoms in the past year because of the pandemic. This was more likely to be reported by participants who: were aged 18-24 years vs. 35-44 (AOR: men 2.25 [95%CI:1.26-4.01], women 2.95[1.42-6.16]); were Black or Black British vs. White (men 2.86 [1.45-5.66], women 1.93 [1.03-8.30]); reported same-sex sex vs. not (past five years; men 2.85 [1.68-4.86], women 5.00 [2.48-10.08]); or ≥1 new relationships vs. not (past year, men 5.85 [3.55-9.66], women 6.38 [3.24-12.59]). Men, but not women, reporting STI-related service use (past year) were more likely to report unmet need for condoms compared to men that did not report service use (3.83 [2.18-6.71]).Discussion: Unmet need for condoms because of the pandemic was more likely to be reported by populations at higher risk of adverse sexual health outcomes, including STI/HIV transmission. Improved access to free/low-cost condoms is crucial for all.
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| 188. |
- Dema, Emily, et al.
(författare)
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Initial impacts of the COVID-19 pandemic on sexual and reproductive health service use and unmet need in Britain : findings from a quasi-representative survey (Natsal-COVID)
- 2022
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Ingår i: The Lancet Public Health. - : Elsevier. - 2468-2667. ; 7:1, s. e36-e47
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The COVID-19 pandemic has affected sexual and reproductive health (SRH) service use and unmet need, but the impact is unknown. We aimed to determine the proportion of participants reporting sexual risk behaviours, SRH service use and unmet need, and to assess remote sexually transmitted infection (STI) testing service use after the first national lockdown in Britain.METHODS: We used data from the National Surveys of Sexual Attitudes and Lifestyles (Natsal)-COVID cross-sectional, quasi-representative web survey (Natsal-COVID Wave 1). Adults aged 18-59 years who resided in England, Scotland, or Wales completed the survey between July 29 and Aug 10, 2020, which included questions about the approximate 4-month period after announcement of the initial lockdown in Britain (March 23, 2020). Quota-based sampling and weighting were used to achieve a quasi-representative population sample. Participants aged 45-59 years were excluded from services analysis due to low rates of SRH service use. Among individuals aged 18-44 years, we estimated reported SRH service use and inability to access, and calculated age-adjusted odds ratios (aORs) among sexually experienced individuals (those reporting any sexual partner in their lifetime) and sexually active individuals (those reporting any sexual partner in the past year). Unweighted denominators and weighted estimates are presented hereafter.FINDINGS: 6654 individuals had complete interviews and were included in the analysis. Among 3758 participants aged 18-44 years, 82·0% reported being sexually experienced, and 73·7% reported being sexually active. 20·8% of sexually experienced participants aged 18-44 years reported using SRH services in the 4-month period. Overall, 9·7% of 3108 participants (9·5% of men; 9·9% of women) reported being unable to use a service they needed, although of the participants who reported trying but not being able to use a SRH service at least once, 76·4% of participants also reported an instance of successful use. 5·9% of 1221 sexually active men and 3·6% of 1560 sexually active women reported use of STI-related services and 14·8% of 1728 sexually experienced women reported use of contraceptive services, with SRH service use highest among individuals aged 18-24 years. Sexually active participants reporting condomless sex with new partners since lockdown were much more likely to report using STI-related services than those who did not report condomless sex (aOR 23·8 [95% CI 11·6-48·9]) for men, 10·5 [3·9-28·2] for women) and, among men, were also more likely to have an unsuccessful attempt at STI-service use (aOR 13·3 [5·3-32·9]). Among 106 individuals who reported using STI testing services, 64·4% accessed services remotely (telephone, video, or online). Among 2581 women aged 25-59 years, 2·4% reported cervical screening compared with an estimated 6% in a comparable 4-month period before the pandemic.INTERPRETATION: Many people accessed SRH care during the initial lockdown; however, young people and those reporting sexual risk behaviours reported difficulties in accessing services and thus such services might need to address a backlog of need.
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| 189. |
- Dewey, Deborah, et al.
(författare)
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Sex-specific associations between maternal phthalate exposure and neurodevelopmental outcomes in children at 2 years of age in the APrON cohort
- 2023
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Ingår i: Neurotoxicology. - 0161-813X .- 1872-9711. ; 98, s. 48-60
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is inconsistent evidence regarding the sex-specific associations between prenatal phthalate exposure and children's neurodevelopment. This could be due to differences in the phthalate exposures inves-tigated and the neurodevelopmental domains assessed.Objective: To evaluate the associations between prenatal phthalate exposure and sex-specific outcomes on measures of cognition, language, motor, executive function, and behaviour in children 2 years of age in the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort.Methods: We evaluated the associations between prenatal phthalate exposure and sex-specific neuro-developmental outcomes in children at 2 years of age using data from 448 mothers and their children (222 girls, 226 boys). Nine phthalate metabolites were measured in maternal urine collected in the second trimester of pregnancy. Children's cognitive, language, and motor outcomes were assessed using the Bayley Scales of Infant Development - Third Edition (Bayley-III). Parents completed questionnaires on children's executive function and behavior, the Behavior Rating Inventory of Executive Function-Preschool Version (BRIEF-P) and Child Behavior Checklist (CBCL), respectively. Sex-stratified robust multivariate regressions were performed.Results: Higher maternal concentrations of & sigma;DEHP and its metabolites were associated with lower scores on the Bayley-III Cognitive (& beta;'s from-11.8 to-0.07 95% CI's from-21.3 to-0.01), Language (& beta;'s from-11.7 to-0. 09, 95% CI's from-22.3 to-0.02) and Motor (& beta;'s from-10.9 to-0.07, 95% CI from-20.4 to-0.01) composites in boys. The patterns of association in girls were in the opposite direction on the Cognitive and Language composites; on the Motor composite they were in the same direction as boys, but of reduced strength. Higher concentrations of & sigma;DEHP and its metabolites were associated with higher scores (i.e., more difficulties) on all measures of executive function in girls: inhibitory self-control (B's from 0.05 to 0.11, 95% CI s from-0.01 to 0.15), flexibility (B's from 0.04 to 0.11, 95% CI s from 0.01 to 0.21) and emergent metacognition (B's from-0.01 to 0.06, 95% CIs from-0.01 to 0.20). Similar patterns of attenuated associations were seen in boys. Higher concentrations of & sigma;DEHP and its metabolites were associated with more Externalizing Problems in girls and boys (B's from 0.03 to 6.82, 95% CIs from-0.08 to 12.0). Two phthalates, MMP and MBP, had sex-specific adverse associations on measures of executive function and behaviour, respectively, while MEP was positively associated with boys' cognitive, language, and motor performance. Limited associations were observed between mixtures of maternal phthalates and sex-specific neurodevelopmental outcomes.Conclusions: Maternal prenatal concentrations of DEHP phthalates were associated with sex specific difference on measures of cognition and language at 2 years of age, specifically, poorer outcomes in boys. Higher exposure to DEHP was associated with poorer motor, executive function, and behavioural outcomes in girls and boys but the strength of these associations differed by sex. Limited associations were noted between phthalate mixtures and child neurodevelopment.
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| 190. |
- Du, Lianlian, et al.
(författare)
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Harnessing cognitive trajectory clusterings to examine subclinical decline risk factors
- 2023
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Ingår i: Brain Communications. - 2632-1297. ; 5:6
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Tidskriftsartikel (refereegranskat)abstract
- Cognitive decline in Alzheimer's disease and other dementias typically begins long before clinical impairment. Identifying people experiencing subclinical decline may facilitate earlier intervention. This study developed cognitive trajectory clusters using longitudinally based random slope and change point parameter estimates from a Preclinical Alzheimer's disease Cognitive Composite and examined how baseline and most recently available clinical/health-related characteristics, cognitive statuses and biomarkers for Alzheimer's disease and vascular disease varied across these cognitive clusters. Data were drawn from the Wisconsin Registry for Alzheimer's Prevention, a longitudinal cohort study of adults from late midlife, enriched for a parental history of Alzheimer's disease and without dementia at baseline. Participants who were cognitively unimpaired at the baseline visit with ≥3 cognitive visits were included in trajectory modelling (n = 1068). The following biomarker data were available for subsets: positron emission tomography amyloid (amyloid: n = 367; [11C]Pittsburgh compound B (PiB): global PiB distribution volume ratio); positron emission tomography tau (tau: n = 321; [18F]MK-6240: primary regions of interest meta-temporal composite); MRI neurodegeneration (neurodegeneration: n = 581; hippocampal volume and global brain atrophy); T2 fluid-attenuated inversion recovery MRI white matter ischaemic lesion volumes (vascular: white matter hyperintensities; n = 419); and plasma pTau217 (n = 165). Posterior median estimate person-level change points, slopes' pre- and post-change point and estimated outcome (intercepts) at change point for cognitive composite were extracted from Bayesian Bent-Line Regression modelling and used to characterize cognitive trajectory groups (K-means clustering). A common method was used to identify amyloid/tau/neurodegeneration/vascular biomarker thresholds. We compared demographics, last visit cognitive status, health-related factors and amyloid/tau/neurodegeneration/vascular biomarkers across the cognitive groups using ANOVA, Kruskal-Wallis, χ2, and Fisher's exact tests. Mean (standard deviation) baseline and last cognitive assessment ages were 58.4 (6.4) and 66.6 (6.6) years, respectively. Cluster analysis identified three cognitive trajectory groups representing steep, n = 77 (7.2%); intermediate, n = 446 (41.8%); and minimal, n = 545 (51.0%) cognitive decline. The steep decline group was older, had more females, APOE e4 carriers and mild cognitive impairment/dementia at last visit; it also showed worse self-reported general health-related and vascular risk factors and higher amyloid, tau, neurodegeneration and white matter hyperintensity positive proportions at last visit. Subtle cognitive decline was consistently evident in the steep decline group and was associated with generally worse health. In addition, cognitive trajectory groups differed on aetiology-informative biomarkers and risk factors, suggesting an intimate link between preclinical cognitive patterns and amyloid/tau/neurodegeneration/vascular biomarker differences in late middle-aged adults. The result explains some of the heterogeneity in cognitive performance within cognitively unimpaired late middle-aged adults.
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