Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 149
Filtrar
1.
Nat Commun ; 12(1): 1078, 2021 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-33597508

RESUMO

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10-8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Feminino , Genótipo , Humanos , Desequilíbrio de Ligação , Pessoa de Meia-Idade , Mutação , Locos de Características Quantitativas/genética , Fatores de Risco
2.
Gut ; 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33632709

RESUMO

OBJECTIVE: An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined. DESIGN: To identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling. RESULTS: We identified 13 loci that reached genome-wide significance (p<5×10-8) and that were not reported by previous GWASs for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer. CONCLUSION: Genetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumour.

3.
Br J Cancer ; 124(4): 842-854, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33495599

RESUMO

BACKGROUND: Epidemiological studies provide strong evidence for a role of endogenous sex hormones in the aetiology of breast cancer. The aim of this analysis was to identify genetic variants that are associated with urinary sex-hormone levels and breast cancer risk. METHODS: We carried out a genome-wide association study of urinary oestrone-3-glucuronide and pregnanediol-3-glucuronide levels in 560 premenopausal women, with additional analysis of progesterone levels in 298 premenopausal women. To test for the association with breast cancer risk, we carried out follow-up genotyping in 90,916 cases and 89,893 controls from the Breast Cancer Association Consortium. All women were of European ancestry. RESULTS: For pregnanediol-3-glucuronide, there were no genome-wide significant associations; for oestrone-3-glucuronide, we identified a single peak mapping to the CYP3A locus, annotated by rs45446698. The minor rs45446698-C allele was associated with lower oestrone-3-glucuronide (-49.2%, 95% CI -56.1% to -41.1%, P = 3.1 × 10-18); in follow-up analyses, rs45446698-C was also associated with lower progesterone (-26.7%, 95% CI -39.4% to -11.6%, P = 0.001) and reduced risk of oestrogen and progesterone receptor-positive breast cancer (OR = 0.86, 95% CI 0.82-0.91, P = 6.9 × 10-8). CONCLUSIONS: The CYP3A7*1C allele is associated with reduced risk of hormone receptor-positive breast cancer possibly mediated via an effect on the metabolism of endogenous sex hormones in premenopausal women.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33500318

RESUMO

BACKGROUND: It is not known if modifiable lifestyle factors that predict survival after invasive breast cancer differ by subtype. METHODS: We analyzed data for 121,435 women diagnosed with breast cancer from 67 studies in the Breast Cancer Association Consortium with 16,890 deaths (8,554 breast cancer-specific) over 10 years. Cox regression was used to estimate associations between risk factors and 10-year all-cause mortality and breast cancer-specific mortality overall, by estrogen receptor (ER) status, and by intrinsic-like subtype. RESULTS: There was no evidence of heterogeneous associations between risk factors and mortality by subtype (adjusted p>0.30). The strongest associations were between all-cause mortality and BMI {greater than or equal to}30 vs 18.5-25 kg/m2 (HR (95%CI): 1.19 (1.06,1.34)); current vs never smoking (1.37 (1.27,1.47)), high vs low physical activity (0.43 (0.21,0.86)), age {greater than or equal to}30 years vs <20 years at first pregnancy (0.79 (0.72,0.86)); >0 to <5 years vs {greater than or equal to}10 years since last full term birth (1.31 (1.11,1.55)); ever vs never use of oral contraceptives (0.91 (0.87,0.96)); ever vs never use of menopausal hormone therapy, including current estrogen-progestin therapy (0.61 (0.54,0.69)). Similar associations with breast cancer mortality were weaker; e.g. 1.11 (1.02,1.21) for current vs never smoking. CONCLUSIONS: We confirm associations between modifiable lifestyle factors and 10-year all-cause mortality. There was no strong evidence that associations differed by ER status or intrinsic-like subtype. IMPACT: Given the large dataset and lack of evidence that associations between modifiable risk factors and 10-year mortality differed by subtype, these associations could be cautiously used in prognostication models to inform patient-centered care.

5.
Cancer Med ; 9(22): 8713-8721, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33022889

RESUMO

BACKGROUND: Depression is more prevalent in breast cancer (BC) survivors than in the general population. However, little is known about depression in long-term survivors. Study objectives were: (1) to compare the age-specific prevalence of depressive symptoms (a) in BC survivors vs female population controls, (b) in disease-free BC survivors vs BC survivors with self-reported recurrence vs controls, and (2) to explore determinants of depression in BC survivors. METHODS: About 3010 BC survivors (stage I-III, 5-16 years post-diagnosis), and 1005 population controls were recruited in German multi-regional population-based studies. Depression was assessed by the Geriatric Depression Scale-15. Prevalence of mild/severe and severe depression only were estimated via logistic regression, controlling for age and education. Multinomial logistic regression was used to explore determinants of mild and severe depression. RESULTS: Compared with population controls, BC survivors were more likely to report mild/severe depression (30.4% vs 23.8%, p = .0003), adjusted for age and education. At all age groups <80 years, prevalence of both mild/severe and severe depression only was significantly higher in BC survivors, while BC survivors ≥80 years reported severe depression less frequently than controls. BC survivors with recurrence reported significantly higher prevalence of mild/severe depression than disease-free survivors and controls, but prevalence in disease-free survivors and controls was comparable. Age, income, living independently, recurrence, and BMI were significant determinants of mild depression in BC survivors. Age, education, employment, income, recurrence, and BMI were significant determinants of severe depression. CONCLUSIONS: Long-term BC survivors <80 years report significantly higher prevalence of depressive symptoms than controls, which might be explained by recurrence and individual factors. The findings suggest that depression in BC survivors is common, and even more after BC recurrence. Clinicians should routinize screening and normalize referral to psychological care.

6.
Cancer Med ; 9(21): 8053-8061, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32893501

RESUMO

BACKGROUND: Fatigue prevalence and severity have been assessed in a variety of studies, yet, not in a standardized way, and predominantly in breast cancer patients. Systematic, comparative investigations across a broad range of cancer entities are lacking. METHODS: The FiX study systematically enrolled 2244 cancer patients across 15 entities approximately 2 years after diagnosis. Fatigue was assessed with the multidimensional EORTC QLQ-FA12 questionnaire. Physical, emotional, cognitive, and total fatigue were compared across entities and with normative values of the general population. Differences in patients' characteristics and cancer therapy between entities were taken into account using analyses of covariance models. RESULTS: Across all entities, mean physical fatigue levels were significantly higher than age- and sex-matched means of the general population for all cancer entities (all Bonferroni-Holm adjusted P < .01). For most entities also emotional and cognitive fatigue levels were significantly higher than normative values. Age- and sex-standardized physical fatigue prevalence ranged from 31.8% among prostate to 51.7% among liver cancer patients. Differences between entities could not be fully explained by sex, age, BMI, or cancer therapy. Adjusted for these factors, mean physical fatigue was higher for stomach (P = .0004), lung (P = .034), kidney (P = .0011), pancreas (P = .081), and endometrium (P = .022) compared to breast cancer patients. Adjusted means of emotional fatigue were also lowest in breast cancer patients and significantly higher in stomach (P = .0047), bladder (P = .0036), and rectal (P = .0020) cancer patients. CONCLUSIONS: Physical, emotional, and cognitive fatigue is prevalent in all 15 investigated cancer entities even 2 years after diagnosis. Fatigue in breast cancer patients, the so-far most studied group, is in the lowest range among all entities, suggesting that the extent of fatigue is still insufficiently determined. Entity-specific problems might need to be considered in the treatment of fatigue.

7.
J Affect Disord ; 276: 159-168, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32697695

RESUMO

BACKGROUND: Studies have reported mixed findings on the relationship between posttraumatic growth (PTG) and health-related quality of life (HRQOL) in cancer survivors. This review aims to give an overview of these studies and to identify potential study- and sample-level factors that could contribute to the heterogeneity of those findings on the relationship between PTG and HRQOL in cancer survivors. METHODS: Multiple electronic databases were systematically searched using the concepts 'posttraumatic growth', 'cancer', and 'health-related quality of life'. Eligible studies (published until 2018) were reviewed, quality-assessed, and effect sizes were extracted and synthesized. RESULTS: Of the 37 included articles, 22 received a rating of 'weak', 11 'moderate' and 4 'strong' in study quality assessment. The overall sample comprised 7954 individuals, mean age of 55.30 years, >50% females, predominantly breast cancer, and survivors mainly within 5 years post-diagnosis. The synthesized results revealed a positive association between PTG and HRQOL (Fisher's z= 0.16) on a total scale, with significant high heterogeneity (I2=75%). Variations in HRQOL measurement and methodological inconsistency contributed to study-level differences of effect sizes. Sample-level characteristics such as geographic region, smaller sample sizes (n < 100) and so on contributed to heterogeneity. LIMITATIONS: Studies assessing the relationship between PTG and HRQOL were heterogeneous, of weak study quality generally, and results were difficult to combine. CONCLUSIONS: Most studies found a positive relationship between the factors suggesting that PTG may play a role for successful coping following cancer. However, studies of higher quality and longitudinal design are needed.

8.
Sci Rep ; 10(1): 9688, 2020 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-32546843

RESUMO

In breast cancer, high levels of homeobox protein Hox-B13 (HOXB13) have been associated with disease progression of ER-positive breast cancer patients and resistance to tamoxifen treatment. Since HOXB13 p.G84E is a prostate cancer risk allele, we evaluated the association between HOXB13 germline mutations and breast cancer risk in a previous study consisting of 3,270 familial non-BRCA1/2 breast cancer cases and 2,327 controls from the Netherlands. Although both recurrent HOXB13 mutations p.G84E and p.R217C were not associated with breast cancer risk, the risk estimation for p.R217C was not very precise. To provide more conclusive evidence regarding the role of HOXB13 in breast cancer susceptibility, we here evaluated the association between HOXB13 mutations and increased breast cancer risk within 81 studies of the international Breast Cancer Association Consortium containing 68,521 invasive breast cancer patients and 54,865 controls. Both HOXB13 p.G84E and p.R217C did not associate with the development of breast cancer in European women, neither in the overall analysis (OR = 1.035, 95% CI = 0.859-1.246, P = 0.718 and OR = 0.798, 95% CI = 0.482-1.322, P = 0.381 respectively), nor in specific high-risk subgroups or breast cancer subtypes. Thus, although involved in breast cancer progression, HOXB13 is not a material breast cancer susceptibility gene.

9.
Cancer Med ; 9(15): 5416-5424, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32524704

RESUMO

BACKGROUND: Nerve-sparing (NS) surgery was developed to improve postoperative sexual and potentially urological outcomes after radical prostatectomy (RP). However, it is largely unknown how NSRP affects health-related quality of life (HRQoL) including urinary and sexual outcomes in prostate cancer (PC) survivors 5-10 years after diagnosis in comparison with Non-NSRP. METHODS: The study population included 382 stage pT2-T3N0M0 PC survivors 5-10 years post diagnosis, who were identified from the multiregional Prostate Cancer Survivorship in Switzerland (PROCAS) study. Briefly, in 2017/2018, PC survivors were identified via six population-based cancer registries based in both German- and French-speaking Switzerland. HRQoL and PC-specific symptom burden was assessed using the EORTC QLQ-C30 and EORTC QLQ-PR25 questionnaires. Differences in HRQoL outcomes between survivors treated with NSRP (uni- & bilateral) and Non-NSRP were analyzed with multivariable linear regression adjusted for age, years since diagnosis, cancer stage, comorbidities at diagnosis, and further therapies, if appropriate. Multiple imputation was performed to minimize the bias due to missing data. RESULTS: Five to ten years after diagnosis, PC survivors treated with NSRP and Non-NSRP reported similar symptom burden and comparable HRQoL function scores. The only significant differences were reported for sexual activity, whereas PC survivors who underwent NSRP reported statistically significant (P = .031) higher sexual activity than those on Non-NSRP. NSRP and Non-NSRP reported similar scores for urinary symptoms and all other HRQoL outcomes. CONCLUSIONS: Our results support nerve-sparing techniques as an option to improve postoperative sexual, but not urinary outcomes after RP in long-term PC survivors.

10.
BMC Cancer ; 20(1): 438, 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32423448

RESUMO

BACKGROUND: Evidence suggests that physical activity (PA) is beneficial for reducing fatigue in colorectal cancer (CRC) survivors. However, little is known regarding long-term effects of PA on fatigue and whether pre-diagnosis PA is associated with less fatigue in the years after diagnosis. Our study aimed to investigate the association of pre- and post-diagnosis PA with long-term fatigue in CRC survivors. METHODS: This study used a German population-based cohort of 1781 individuals, diagnosed with CRC in 2003-2014, and alive at five-year follow-up (5YFU). Physical activity was assessed at diagnosis and at 5YFU. Fatigue was assessed by the Fatigue Assessment Questionnaire and the EORTC Quality of Life Questionnaire-Core 30 fatigue subscale at 5YFU. Multivariable linear regression was used to explore associations between pre- and post-diagnosis PA and fatigue at 5YFU. RESULTS: No evidence was found that pre-diagnosis PA was associated with less fatigue in long-term CRC survivors. Pre-diagnosis work-related PA and vigorous PA were even associated with higher levels of physical (Beta (ß) = 2.52, 95% confidence interval (CI) = 1.14-3.90; ß = 2.03, CI = 0.65-3.41), cognitive (ß = 0.17, CI = 0.05-0.28; ß = 0.13, CI = 0.01-0.25), and affective fatigue (ß = 0.26, CI = 0.07-0.46; ß = 0.21, CI = 0.02-0.40). In cross-sectional analyses, post-diagnosis PA was strongly associated with lower fatigue on all scales. CONCLUSIONS: In this study, pre-diagnosis PA does not appear to be associated with less fatigue among long-term CRC survivors. Our results support the importance of ongoing PA in long-term CRC survivors. Our findings might be used as a basis for further research on specific PA interventions to improve the long-term outcome of CRC survivors.

11.
Nat Genet ; 52(6): 572-581, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32424353

RESUMO

Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype1-3. To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P < 5.0 × 10-8), 15 of which showed evidence for associations with at least one tumor feature (false discovery rate < 0.05). Five loci showed associations (P < 0.05) in opposite directions between luminal and non-luminal subtypes. In silico analyses showed that these five loci contained cell-specific enhancers that differed between normal luminal and basal mammary cells. The genetic correlations between five intrinsic-like subtypes ranged from 0.35 to 0.80. The proportion of genome-wide chip heritability explained by all known susceptibility loci was 54.2% for luminal A-like disease and 37.6% for triple-negative disease. The odds ratios of polygenic risk scores, which included 330 variants, for the highest 1% of quantiles compared with middle quantiles were 5.63 and 3.02 for luminal A-like and triple-negative disease, respectively. These findings provide an improved understanding of genetic predisposition to breast cancer subtypes and will inform the development of subtype-specific polygenic risk scores.


Assuntos
Neoplasias da Mama/genética , Estudo de Associação Genômica Ampla , Proteína BRCA1/genética , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Desequilíbrio de Ligação , Mutação , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia
12.
J Natl Cancer Inst ; 2020 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-32359158

RESUMO

We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72,284 cases and 80,354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression, and a newly developed case-only method, for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history), and on average 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer.

13.
Cancer Prev Res (Phila) ; 13(7): 611-622, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32253267

RESUMO

Evidence suggests that physical activity (PA) is positively associated with (health-related) quality of life (QOL) in colorectal cancer survivors. However, little is known regarding long-term effects of PA on QOL and if prediagnosis PA is associated with QOL in the years after diagnosis. Our study aimed to investigate the association of prediagnosis and postdiagnosis PA with long-term QOL in colorectal cancer survivors.This study is based on a population-based cohort from Germany of 1,781 newly diagnosed colorectal cancer survivors over a 5-year period. PA was assessed at diagnosis and at 5-year follow-up (5YFU). Quality of life was assessed by the European Organisation for Research and Treatment of Cancer C Quality of Life Questionnaire QLQ-C30 at 5YFU. Multivariable linear regression was used to explore associations between prediagnosis and postdiagnosis PA and QOL at 5YFU.No evidence of a positive association between higher levels of prediagnosis PA and better long-term QOL was found. Higher levels of prediagnosis work-related PA and vigorous PA were even associated with decreased QOL in domains such as cognitive [Beta(ß) = -2.52, 95% confidence interval (CI) = -3.77, -1.27; ß = -1.92, CI = -3.17, -0.67) and emotional functioning (ß = -2.52, CI = -3.84, -1.19; ß = -2.12, CI = -3.44, -0.80). In cross-sectional analyses, higher postdiagnosis PA was strongly associated with higher QOL. Survivors physically active at both prediagnosis and postdiagnosis as well as survivors who increased their PA between prediagnosis and postdiagnosis reported significantly higher long-term QOL compared with survivors who remained inactive at prediagnosis and postdiagnosis. In this study, higher prediagnosis PA does not appear to be associated with higher QOL among long-term colorectal cancer survivors but our results support the importance of ongoing PA throughout survivorship.

14.
Genet Epidemiol ; 44(5): 442-468, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32115800

RESUMO

Previous transcriptome-wide association studies (TWAS) have identified breast cancer risk genes by integrating data from expression quantitative loci and genome-wide association studies (GWAS), but analyses of breast cancer subtype-specific associations have been limited. In this study, we conducted a TWAS using gene expression data from GTEx and summary statistics from the hitherto largest GWAS meta-analysis conducted for breast cancer overall, and by estrogen receptor subtypes (ER+ and ER-). We further compared associations with ER+ and ER- subtypes, using a case-only TWAS approach. We also conducted multigene conditional analyses in regions with multiple TWAS associations. Two genes, STXBP4 and HIST2H2BA, were specifically associated with ER+ but not with ER- breast cancer. We further identified 30 TWAS-significant genes associated with overall breast cancer risk, including four that were not identified in previous studies. Conditional analyses identified single independent breast-cancer gene in three of six regions harboring multiple TWAS-significant genes. Our study provides new information on breast cancer genetics and biology, particularly about genomic differences between ER+ and ER- breast cancer.


Assuntos
Neoplasias da Mama/genética , Estudo de Associação Genômica Ampla , Receptores Estrogênicos/metabolismo , Neoplasias da Mama/metabolismo , Estrogênios/metabolismo , Feminino , Predisposição Genética para Doença , Genômica , Humanos , Medição de Risco , Transcriptoma , Proteínas de Transporte Vesicular/genética
15.
BMC Cancer ; 20(1): 87, 2020 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-32013907

RESUMO

Following publication of the original article [1], an error was reported in the author group. The correct author group should read as follows.

16.
Curr Treat Options Oncol ; 21(2): 17, 2020 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-32025928

RESUMO

OPINION STATEMENT: Cancer-related fatigue (CRF) is a problem for a significant proportion of cancer survivors during and after active cancer treatment. However, CRF is underdiagnosed and undertreated. Interventions are available for CRF although there is no gold standard. Based on current level of evidence, exercise seems to be most effective in preventing or ameliorating CRF during the active- and posttreatment phases.

17.
Artigo em Inglês | MEDLINE | ID: mdl-32042437

RESUMO

Background: Patients with metastatic breast cancer (MBC) are treated with a palliative approach with focus on controlling for disease symptoms and maintaining high quality of life. Information on individual needs of patients and their relatives as well as on treatment patterns in clinical routine care for this specific patient group are lacking or are not routinely documented in established Cancer Registries. Thus, we developed a registry concept specifically adapted for these incurable patients comprising primary and secondary data as well as mobile-health (m-health) data. Methods: The concept for patient-centered "Breast cancer care for patients with metastatic disease" (BRE-4-MED) registry was developed and piloted exemplarily in the region of Main-Franconia, a mainly rural region in Germany comprising about 1.3 M inhabitants. The registry concept includes data on diagnosis, therapy, progression, patient-reported outcome measures (PROMs), and needs of family members from several sources of information including routine data from established Cancer Registries in different federal states, treating physicians in hospital as well as in outpatient settings, patients with metastatic breast cancer and their family members. Linkage with routine cancer registry data was performed to collect secondary data on diagnosis, therapy, and progression. Paper and online-based questionnaires were used to assess PROMs. A dedicated mobile application software (APP) was developed to monitor needs, progression, and therapy change of individual patients. Patient's acceptance and feasibility of data collection in clinical routine was assessed within a proof-of-concept study. Results: The concept for the BRE-4-MED registry was developed and piloted between September 2017 and May 2018. In total n = 31 patients were included in the pilot study, n = 22 patients were followed up after 1 month. Record linkage with the Cancer Registries of Bavaria and Baden-Württemberg demonstrated to be feasible. The voluntary APP/online questionnaire was used by n = 7 participants. The feasibility of the registry concept in clinical routine was positively evaluated by the participating hospitals. Conclusion: The concept of the BRE-4-MED registry provides evidence that combinatorial evaluation of PROMs, needs of family members, and raising clinical parameters from primary and secondary data sources as well as m-health applications are feasible and accepted in an incurable cancer collective.

18.
Cancer Epidemiol Biomarkers Prev ; 29(4): 860-870, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32051193

RESUMO

BACKGROUND: Results from epidemiologic studies examining polyunsaturated fatty acids (PUFA) and colorectal cancer risk are inconsistent. Mendelian randomization may strengthen causal inference from observational studies. Given their shared metabolic pathway, examining the combined effects of aspirin/NSAID use with PUFAs could help elucidate an association between PUFAs and colorectal cancer risk. METHODS: Information was leveraged from genome-wide association studies (GWAS) regarding PUFA-associated SNPs to create weighted genetic scores (wGS) representing genetically predicted circulating blood PUFAs for 11,016 non-Hispanic white colorectal cancer cases and 13,732 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Associations per SD increase in the wGS were estimated using unconditional logistic regression. Interactions between PUFA wGSs and aspirin/NSAID use on colorectal cancer risk were also examined. RESULTS: Modest colorectal cancer risk reductions were observed per SD increase in circulating linoleic acid [ORLA = 0.96; 95% confidence interval (CI) = 0.93-0.98; P = 5.2 × 10-4] and α-linolenic acid (ORALA = 0.95; 95% CI = 0.92-0.97; P = 5.4 × 10-5), whereas modest increased risks were observed for arachidonic (ORAA = 1.06; 95% CI = 1.03-1.08; P = 3.3 × 10-5), eicosapentaenoic (OREPA = 1.04; 95% CI = 1.01-1.07; P = 2.5 × 10-3), and docosapentaenoic acids (ORDPA = 1.03; 95% CI = 1.01-1.06; P = 1.2 × 10-2). Each of these effects was stronger among aspirin/NSAID nonusers in the stratified analyses. CONCLUSIONS: Our study suggests that higher circulating shorter-chain PUFAs (i.e., LA and ALA) were associated with reduced colorectal cancer risk, whereas longer-chain PUFAs (i.e., AA, EPA, and DPA) were associated with an increased colorectal cancer risk. IMPACT: The interaction of PUFAs with aspirin/NSAID use indicates a shared colorectal cancer inflammatory pathway. Future research should continue to improve PUFA genetic instruments to elucidate the independent effects of PUFAs on colorectal cancer.

19.
Nat Commun ; 11(1): 312, 2020 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-31949161

RESUMO

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 ~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.


Assuntos
Neoplasias da Mama/genética , Variação Genética , Estudo de Associação Genômica Ampla , Células Germinativas , Apoptose , Relógios Circadianos , Biologia Computacional , Feminino , Subunidades alfa de Proteínas de Ligação ao GTP/genética , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/genética , Redes Reguladoras de Genes , Genótipo , Humanos , Prognóstico , Receptores Estrogênicos/genética , Transdução de Sinais
20.
BMC Cancer ; 20(1): 51, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31964352

RESUMO

BACKGROUND: More people than ever before are currently living with a diagnosis of cancer and the number of people concerned is likely to continue to rise. Cancer survivors are at risk of developing a second primary cancer (SPC). This study aims to investigate the risk of SPC in Switzerland. METHODS: The study cohort included all patients with a first primary cancer recorded in 9 Swiss population-based cancer registries 1981-2009 who had a minimum survival of 6 months, and a potential follow-up until the end of 2014. We calculated standardized incidence ratios (SIR) to estimate relative risks (RR) of SPC in cancer survivors compared with the cancer risk of the general population. SIR were stratified by type of first cancer, sex, age and period of first diagnosis, survival period and site of SPC. RESULTS: A total of 33,793 SPC were observed in 310,113 cancer patients. Both male (SIR 1.18, 95%CI 1.16-1.19) and female (SIR 1.20, 95%CI 1.18-1.22) cancer survivors had an elevated risk of developing a SPC. Risk estimates varied substantially according to type of first cancer and were highest in patients initially diagnosed with cancer of the oral cavity and pharynx, Hodgkin lymphoma, laryngeal, oesophageal, or lung cancer. Age-stratified analyses revealed a tendency towards higher RR in patients first diagnosed at younger ages. Stratified by survival period, risk estimates showed a rising trend with increasing time from the initial diagnosis. We observed strong associations between particular types of first and SPC, i.e. cancer types sharing common risk factors such as smoking or alcohol consumption (e.g. repeated cancer of the oral cavity and pharynx (SIRmales 20.12, 95%CI 17.91-22.33; SIRfemales 37.87, 95%CI 30.27-45.48). CONCLUSION: Swiss cancer survivors have an increased risk of developing a SPC compared to the general population, particularly patients first diagnosed before age 50 and those surviving more than 10 years. Cancer patients should remain under continued surveillance not only for recurrent cancers but also for new cancers. Some first and SPCs share lifestyle associated risk factors making it important to promote healthier lifestyles in both the general population and cancer survivors.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Sobreviventes de Câncer/estatística & dados numéricos , Segunda Neoplasia Primária/patologia , Neoplasias/complicações , Fumar/efeitos adversos , Adolescente , Adulto , Idoso , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias/terapia , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/etiologia , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Suíça/epidemiologia , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...