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1.
Dis Colon Rectum ; 62(11): 1294-1304, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31567919

RESUMO

BACKGROUND: Despite the increasing number of younger individuals diagnosed with colon and rectal cancer, research on the long-term disease-specific health-related quality of life of younger (<50 years) survivors of colon and rectal cancer is scarce. OBJECTIVE: Our study aimed to compare disease-specific functional deficits and symptoms of survivors of colon and rectal cancer 5 to 16 years postdiagnosis, stratified by age at diagnosis and by sex. DESIGN: This is a cross-sectional study. SETTING: We used data from the population-based CAncEr Survivorship-A multi-Regional study in collaboration with 5 population-based German cancer registries. PATIENTS: Survivors of colon and rectal cancer were included in the study. MAIN OUTCOME MEASURES: Respondents completed the disease-specific European Organization for Research and Treatment of Cancer Quality of Life colorectal cancer module. Age at diagnosis categories were <50, 50 to 59, 60 to 69, and ≥70 years. Least square mean health-related quality of life scores, derived from linear regression, were adjusted for sex, education, time since diagnosis, cancer site, cancer stage, and treatment, where appropriate. RESULTS: The sample comprised 697 survivors of colon cancer and 479 survivors of rectal cancer. In general, survivors of colon and rectal cancer diagnosed at <50 years of age reported lower functioning and higher symptom burden in comparison with survivors diagnosed at an older age. When stratified by sex, female survivors of colon cancer tended to report more concerns with hair loss but fewer sexual problems when compared with male survivors of colon cancer of the same age. Female survivors of rectal cancer in all age groups tended to report lower levels of sexual interest than male survivors of rectal cancer of the same age. LIMITATIONS: This was a cross-sectional study with findings that could be biased toward healthier long-term survivors. The generalizability of results is limited to survivors diagnosed before 2005. CONCLUSIONS: Our results suggest that supportive care for survivors of colon and rectal cancer to improve their self-management of symptoms should be adapted according to cancer type, age at diagnosis, and sex. See Video Abstract at http://links.lww.com/DCR/B29. LA EDAD AL DIAGNÓSTICO Y EL GÉNERO ESTÁN ASOCIADOS CON DÉFICITS A LARGO PLAZO EN LA CALIDAD DE VIDA RELACIONADA CON LA SALUD ESPECíFICA DE LA ENFERMEDAD DE LOS SOBREVIVIENTES DE CÁNCER DE COLON Y RECTO: UN ESTUDIO BASADO EN LA POBLACIÓN:: A pesar del creciente número de individuos jóvenes diagnosticados con cáncer de colon y recto, la investigación sobre la calidad de vida relacionada con la salud específica de la enfermedad a largo plazo de los sobrevivientes de cáncer de colon y recto jóvenes (<50 años) es escasa.Nuestro estudio tuvo como objetivo comparar los déficits funcionales específicos de la enfermedad y los síntomas de los sobrevivientes de cáncer de colon y recto 5-16 años después del diagnóstico, estratificados por edad al momento del diagnóstico y por género.Transversal.Utilizamos datos del estudio Supervivencia de CAncEr basada en la población: Un estudio multirregional en colaboración con cinco bases de datos alemanas de cáncer basados en la población.Sobrevivientes de cáncer de colon y recto.Los encuestados respondieron el módulo de calidad de vida específica para la enfermedad en cáncer colorrectal de la Organización Europea para la Investigación y Tratamiento del Cáncer. Las categorías de edad al diagnóstico fueron <50, 50-59, 60-69 y ≥70 años. Los puntajes de CVRS (calidad de vida relacionada a la salud) medios mínimos cuadrados, derivados de la regresión lineal, se ajustaron por género, educación, tiempo desde el diagnóstico, sitio del cáncer, etapa del cáncer y tratamiento, cuando apropiado.La muestra comprendió 697 y 479 sobrevivientes de cáncer de colon y de recto, respectivamente. En general, los sobrevivientes de cáncer de colon y recto diagnosticados con <50 años de edad reportaron una menor funcionalidad y una mayor carga de síntomas en comparación con los sobrevivientes diagnosticados a una edad más avanzada. Cuando se estratificaron por género, las mujeres sobrevivientes de cáncer de colon tendieron a informar más preocupaciones sobre la pérdida de cabello pero menos problemas sexuales en comparación con los hombres sobrevivientes de colon de la misma edad. Las mujeres sobrevivientes de cáncer rectal en todos los grupos de edad tendieron a informar niveles más bajos de interés sexual que los hombres sobrevivientes de cáncer rectal de la misma edad.Estudio transversal con hallazgos que podrían estar sesgados hacia sobrevivientes a largo plazo más saludables. La generalización de los resultados se limitó a los sobrevivientes diagnosticados antes de 2005.Nuestros resultados sugieren que los cuidados de soporte para los sobrevivientes de cáncer de colon y recto para mejorar su automanejo de síntomas deben adaptarse según el tipo de cáncer, la edad en el momento del diagnóstico y el género. Vea el resumen en video en http://links.lww.com/DCR/B29.

2.
Gesundheitswesen ; 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31663107

RESUMO

Population-based cancer registries have a long-standing role in cancer monitoring. Scientific use of cancer registry data is one important purpose of cancer registration, but use of cancer registry data is not restricted to cancer registries. Cancer registration in Germany is currently heading towards population-based collection of detailed clinical data. This development together with additional options for record linkage and long-term follow-up will offer new opportunities for health services and outcome research. Both regional population-based registries and the German Centre for Cancer Registry Data (ZfKD) at the Robert Koch-Institute as well as international cancer registries and consortia or organizations may provide external researchers access to individual or aggregate level data for secondary data analysis. In this review, we elaborate on the access to cancer registry data for research purposes, availability of specific data items, and options for data linkage with external data sources. We also discuss as well as on limitations in data availability and quality, and describe typical biases in design and analysis.

3.
Cancer Epidemiol ; 63: 101596, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31520938

RESUMO

BACKGROUND: Research on soft-tissue sarcoma (STS) and bone sarcoma (BS) is increasingly in the focus of physicians and pharmaceutical companies. Expanding knowledge has improved the management of sarcoma and possibly survival. Here we provide the first population-based data on time trends of incidence, mortality, and survival of STS and BS diagnosed in Switzerland between 1996 and 2015. METHODS: We performed a retrospective registry study with data from the National Institute for Cancer Epidemiology and Registration (NICER) database in Switzerland between 1996 and 2015. RESULTS: We identified 5384 STS patients and 940 BS patients. The three most common STS subtypes were undifferentiated/unclassified sarcoma (22.3%), liposarcoma (20.6%) and leiomyosarcoma (20.6%). Chondrosarcoma, osteosarcoma and Ewing sarcoma represented 40.4%, 27.0% and 15.2% of the BS group, respectively. The age-standardized incidence and mortality rates in 2011-2015 were 4.43 and 1.42 per 100,000 person-years for STS, and 0.91 and 0.42 for BS. Age-standardized incidence of STS in males was significantly higher during 1996-2000 than during 2001-2015; however, mortality rates did not change significantly over time. Five-year relative survival (RS) for STS improved significantly from 56.4% (95%CI 52.9-59.7 for 1996-2001) to 61.6% (95%CI 58.6-64.4 for 2011-2015) (p = 0.025). No improvement in 5-year RS for BS could be observed (RS 1996-2000: 69.6%, 95%CI 61.2-76.6; RS 2011-2015: 73.1%, 95%CI 66.6-78.6; p = 0.479). CONCLUSION: Incidence rates of STS and BS have been stable since 2001. The longer RS in STS can be attributed to advances in sarcoma patient management.

4.
Sci Rep ; 9(1): 12524, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31467304

RESUMO

Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44-1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.

5.
Eur J Cancer Care (Engl) ; 28(5): e13076, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31050091

RESUMO

OBJECTIVE: Several therapies for localised prostate cancer (PC) are available; all yield similar survival rates. However, each therapy has significant side effects that can influence patients' health-related quality of life (HRQoL) in the long run. METHODS: The study sample included 911 survivors with localised PC, 5-15 years post-diagnosis who were identified from the population-based CAESAR + study in Germany. HRQoL was assessed using the EORTC QLQ-C30 and EORTC QLQ-PR25 questionnaires. The association between type of therapy and HRQoL was assessed with multivariable linear regression and global F-test adjusting for age, time since diagnosis and comorbidities. RESULTS: Overall, survivors treated with radical prostatectomy (RP) or radiotherapy (RT) alone reported the best HRQoL and the lowest symptom burden. Conversely, survivors treated with androgen deprivation therapy (ADT) (& RP/RT) or RP & RT (in combination) reported the worst HRQoL and the highest symptom burden. Significant differences among treatment groups in HRQoL were found for global health status (p = 0.041), social functioning (p = 0.007), urinary symptoms (p = 0.035), bowel symptoms (p = 0.017) and hormonal treatment-related symptoms (p < 0.001) among other symptoms. CONCLUSIONS: Long-term localised PC survivors formerly treated with a combination of RP and RT or with ADT report poorer HRQoL and more symptoms than patients treated with either RP or RT alone.

6.
Cancer Med ; 8(6): 3227-3236, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31012272

RESUMO

PURPOSE: Cancer-related fatigue (CRF) is one of the most prevalent symptoms experienced by cancer survivors. However, researchers are only beginning to elucidate the risk factors, underlying mechanism(s), and its association with other outcomes. Research on the association between CRF and mortality is limited. METHODS: The study sample comprised 2059 short-term (<5 years postdiagnosis) cancer survivors from four PROFILES registry studies. Survivors diagnosed with stage I-III colorectal cancer (CRC) or stage I-III endometrial cancer (EC), with no evidence of disease, were identified and followed-up by the Netherlands Cancer Registry. Fatigue was assessed with the Fatigue Assessment Scale. Cox proportional hazards models adjusted for demographic, clinical, and lifestyle characteristics were performed to assess the association of CRF with all-cause mortality. Date of censoring was February 1, 2017. RESULTS: Prevalence of CRF varied between 35.8% (male CRC) and 43.6% (female CRC). After a median follow-up period of 9.0 years, a total of 408 survivors (20%) had died. CRF was associated with increased all-cause mortality in male CRC survivors (HRadj = 1.75, 95% CI [1.31-2.33]). This association remained statistically significant after excluding survivors experiencing anhedonia. For female CRC (HRadj = 1.32, 95% CI [0.90-1.97]) and EC (HRadj = 1.27, 95% CI [0.84-1.90]) survivors, there was no significant association with all-cause mortality for the fatigued group in multivariable analyses. CONCLUSION: Our study found that CRF is significantly associated with all-cause mortality in male CRC survivors, irrespective of potential confounders. This result suggests that clinicians should increase their attention towards the recognition and treatment of CRF.

7.
Nat Commun ; 10(1): 1741, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30988301

RESUMO

Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.


Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença , Feminino , Perfilação da Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , Locos de Características Quantitativas
8.
Breast Cancer Res Treat ; 175(2): 499-510, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30826935

RESUMO

PURPOSE: Little is known about breast cancer (BC) survivors' health-related quality of life (HRQoL) > 5 or even > 10 years past diagnosis. It is of interest whether, in the long run, survivors' HRQoL aligns with that of the general population. Study objectives were to (1) compare disease-free BC survivors' HRQoL to that of non-cancer controls, and (2) compare long-term survivors (LTS, 5-9 years post-diagnosis), very long-term survivors (VLTS, ≥ 10 years post-diagnosis), and controls with respect to their HRQoL. METHODS: The samples of 2647 disease-free BC survivors (5-16 years post-diagnosis) and 1005 population controls were recruited in German multi-regional population-based studies. HRQoL was assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). Differences in HRQoL were assessed with multiple regression, controlling for age and education. RESULTS: Disease-free BC survivors < 80 years (at survey) reported overall global health status/quality of life comparable to controls, but statistically significant lower physical, role, emotional, social, and cognitive functioning. They also indicated more fatigue, insomnia, dyspnoea, and financial difficulties. However, differences were only of trivial or small clinical relevance. At age 80-89, no differences between BC survivors and controls were observed. Deficits in emotional and cognitive functioning and some symptoms (e.g. insomnia and fatigue) persist, as both LTS and VLTS reported more detriments than controls. CONCLUSIONS: In view of the persistent, small but significant detriments in disease-free BC survivors' cognitive and emotional functioning and higher symptom burden, possibilities to prevent detriments from becoming chronic should be explored.

9.
Br J Cancer ; 120(6): 647-657, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30787463

RESUMO

BACKGROUND: We examined the associations between germline variants and breast cancer mortality using a large meta-analysis of women of European ancestry. METHODS: Meta-analyses included summary estimates based on Cox models of twelve datasets using ~10.4 million variants for 96,661 women with breast cancer and 7697 events (breast cancer-specific deaths). Oestrogen receptor (ER)-specific analyses were based on 64,171 ER-positive (4116) and 16,172 ER-negative (2125) patients. We evaluated the probability of a signal to be a true positive using the Bayesian false discovery probability (BFDP). RESULTS: We did not find any variant associated with breast cancer-specific mortality at P < 5 × 10-8. For ER-positive disease, the most significantly associated variant was chr7:rs4717568 (BFDP = 7%, P = 1.28 × 10-7, hazard ratio [HR] = 0.88, 95% confidence interval [CI] = 0.84-0.92); the closest gene is AUTS2. For ER-negative disease, the most significant variant was chr7:rs67918676 (BFDP = 11%, P = 1.38 × 10-7, HR = 1.27, 95% CI = 1.16-1.39); located within a long intergenic non-coding RNA gene (AC004009.3), close to the HOXA gene cluster. CONCLUSIONS: We uncovered germline variants on chromosome 7 at BFDP < 15% close to genes for which there is biological evidence related to breast cancer outcome. However, the paucity of variants associated with mortality at genome-wide significance underpins the challenge in providing genetic-based individualised prognostic information for breast cancer patients.

10.
Acta Oncol ; 58(5): 801-810, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30736716

RESUMO

Background: Previous research suggests an age differential in health-related quality of life (HRQOL) among long-term (5-10 years post-diagnosis, LTS) colorectal cancer (CRC) survivors. Few studies have specifically addressed the association of age differentials with HRQOL for very long-term CRC survivors (>10 years post-diagnosis, VLTS) and non-cancer population controls. We aimed to assess possible deficits in HRQOL of disease-free CRC-LTS and CRC-VLTS in comparison with non-cancer population controls, and whether the observed pattern varies by age and time since diagnosis. Methods: We used data from the CAncEr Survivorship - A multi-Regional (CAESAR+) study in collaboration with five population-based German cancer registries. HRQOL from controls was accessed from the Lebensqualität in DEeutschland (LinDE) study. All respondents completed the European Organization for Research and Treatment of Cancer Quality of Life Core-30 questionnaire. We calculated least square means of HRQOL scores. Analyses were adjusted for age, sex, and education, where appropriate. Results: The sample included 862 CRC-LTS, 400 CRC-VLTS and 1689 controls. CRC survivors reported overall good HRQOL but significantly poorer social functioning and more problems with dyspnea, constipation, diarrhea and finances than controls. When stratified by age, deficits in functioning and global health, and more problems with symptoms and finances were noted mainly among younger CRC survivors. Further stratification by time since diagnosis showed that similar deficits in HRQOL and symptoms were noted mainly among the younger CRC-LTS group when compared with controls. Generally, CRC-VLTS reported comparable HRQOL to controls. An exception was noted for diarrhea, whereby CRC survivors, regardless of age and time since diagnosis, reported significantly more problems with this symptom than controls. Conclusions: In comparison with non-cancer controls, disease-free CRC survivors reported overall good HRQOL but experience persistent specific detriments in HRQOL many years after diagnosis. In age stratified analyses, HRQOL deficits were noted mainly among younger CRC-LTS.

11.
Acta Oncol ; 58(5): 811-818, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30777496

RESUMO

Background: With improving prognosis, the ability to return to work after cancer has become a realistic goal but only little is known regarding details such as sustainability, financial consequences, and potential determinants of return to work in long-term survivors in Germany. Methods: We studied return to work in a population-based sample of 1558 long-term cancer survivors, diagnosed in 1994-2004 with breast, colorectal or prostate cancer before age 60 (mean 50.1). Information regarding employment status and financial difficulties was obtained via mailed questionnaires from patients who were identified by six population-based cancer registries in Germany. Cumulative incidence of return to work was determined by time-to-event analysis with consideration of competing events. Chi2 tests and multiple logistic regression modeling were employed to identify potential sociodemographic and clinical determinants of return to work. Results: Within a mean period since diagnosis of 8.3 years, 63% of all working-age cancer survivors initially returned to their old job and another 7% took up a new job. Seventeen percent were granted a disability pension, 6% were early retired (not cancer-related), 4% became unemployed, and 1% left the job market for other reasons. Resumption of work occurred within the first 2 years after diagnosis in 90% of all returnees. Cancer-related reduction of working hours was reported by 17% among all returnees and 6% quit their job due to cancer within 5 years past return to work. The probability of return to work was strongly related with age at diagnosis, tumor stage, education, and occupational class but did not differ with respect to the tumor site, gender nor marital status. Conclusions: Most long-term survivors after breast, colorectal, or prostate cancer of working-age are able to return to work. However, financial problems might arise due to a reduction in working hours. An additional provision of targeted interventions for high-risk groups should be discussed.

12.
Cancer Epidemiol ; 59: 51-57, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30690330

RESUMO

BACKGROUND: Chronic myelomonocytic leukemia (CMML) is a rare hematopoietic malignancy. Treatment with hypomethylating agents (HMA) was introduced between 2004 and 2006 but its impact on population-based survival remains controversial. The aim of this study was to investigate epidemiological characteristics and survival before and after introduction of HMA treatment. METHODS: We performed a population-based analysis of CMML cases reported to the Cantonal Cancer Registries in Switzerland (SWISS) and the Surveillance, Epidemiology, and End Results (SEER) Program from the United States for 1999-2006 (before HMA) and 2007-2014 (after HMA). Time trends were compared for these two time periods. RESULTS: 423 and 4144 new CMML cases were reported to the SWISS and SEER registries, respectively. We observed an increasing proportion of older patients ≥75 years in the SWISS (50.3%-62.3%) compared to a decreasing one in the SEER population (59.1%-55.1%). Age standardized incidence-rates were similar and remained stable in both countries (0.32-0.38 per 100'000 py). Relative survival (RS) improved significantly in the SEER (3 years 27%-37%; 5 years 19%-23%; p < 0.001 for both) but remained stable in the SWISS population (3 years 48% to 40%; 5 years 34% to 26%; n.s. for both). CONCLUSIONS: With the exception of opposing age-trends, epidemiologic characteristics are similar in both countries and comparable to other population-based registries. RS remains poor and different time trends of population-based survival cannot be faithfully explained by HMA but most likely by changes in diagnostic accuracy within prognostically distinct age-groups.

13.
JAMA Cardiol ; 4(2): 163-173, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30649175

RESUMO

Importance: It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE). Objective: To estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism. Design, Setting, and Participants: This study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731 728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421 537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018. Exposures: A panel of several established cardiovascular risk factors. Main Outcomes and Measures: Hazard ratios (HRs) per 1-SD higher usual risk factor levels (or presence/absence). Incident fatal outcomes in ERFC (VTE, 1041; coronary heart disease [CHD], 25 131) and incident fatal/nonfatal outcomes in UK Biobank (VTE, 2321; CHD, 3385). Hazard ratios were adjusted for age, sex, smoking status, diabetes, and body mass index (BMI). Results: Of the 731 728 participants from the ERFC, 403 396 (55.1%) were female, and the mean (SD) age at the time of the survey was 51.9 (9.0) years; of the 421 537 participants from the UK Biobank, 233 699 (55.4%) were female, and the mean (SD) age at the time of the survey was 56.4 (8.1) years. Risk factors for VTE included older age (ERFC: HR per decade, 2.67; 95% CI, 2.45-2.91; UK Biobank: HR, 1.81; 95% CI, 1.71-1.92), current smoking (ERFC: HR, 1.38; 95% CI, 1.20-1.58; UK Biobank: HR, 1.23; 95% CI, 1.08-1.40), and BMI (ERFC: HR per 1-SD higher BMI, 1.43; 95% CI, 1.35-1.50; UK Biobank: HR, 1.37; 95% CI, 1.32-1.41). For these factors, there were similar HRs for pulmonary embolism and deep vein thrombosis in UK Biobank (except adiposity was more strongly associated with pulmonary embolism) and similar HRs for unprovoked vs provoked VTE. Apart from adiposity, these risk factors were less strongly associated with VTE than CHD. There were inconsistent associations of VTEs with diabetes and blood pressure across ERFC and UK Biobank, and there was limited ability to study lipid and inflammation markers. Conclusions and Relevance: Older age, smoking, and adiposity were consistently associated with higher VTE risk.

14.
Am J Hum Genet ; 104(1): 21-34, 2019 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-30554720

RESUMO

Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57-1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628-0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.

15.
Support Care Cancer ; 27(1): 275-286, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29951713

RESUMO

PURPOSE: Many long-term cancer survivors still have to adjust to possible adverse consequences of the illness or treatment. Resources can play an important role in this adjustment process, but research on this topic is limited, especially for very long-term survivors. This study explores, which resources are most frequently indicated by different subgroups of cancer survivors, and what role resources play for functioning and health-related quality of life (HRQL) in cancer survivors with and without recurrence. METHODS: The sample of 6030 breast, colorectal, and prostate cancer survivors (5-16 years post-diagnosis) was recruited in a German multi-regional population-based study. Personal resources were assessed by a 27-item checklist; HRQL was assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). General linear models were used to analyze associations of resources with HRQL. RESULTS: Participants indicated on average 11.4 (SD 5.1) resources as helpful. Family, activities with others, and partnership were indicated most commonly overall, but frequencies varied according to age, sex, and tumor site. Physical activity, health, professional help, calmness, hope, optimism, and hobbies were most important in explaining HRQL variance. Cancer survivors with recurrence and many resources were found to report similar HRQL as survivors without recurrence and only few resources. CONCLUSIONS: The study underlines the importance and situational variability of personal and social resources for cancer survivors' HRQL, even years post-diagnosis. Not only the availability, but also the individual perception and significance of resources should be considered in follow-up cancer care.


Assuntos
Neoplasias da Mama/psicologia , Neoplasias Colorretais/psicologia , Neoplasias da Próstata/psicologia , Qualidade de Vida/psicologia , Adulto , Idoso , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Sobreviventes de Câncer , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Recursos em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Sobreviventes/psicologia , Adulto Jovem
16.
Nat Genet ; 2018 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-30510241

RESUMO

To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 × 10-8, bringing the number of known independent signals for CRC to ~100. New signals implicate lower-frequency variants, Krüppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.

17.
Int J Epidemiol ; 2018 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-30476131

RESUMO

Background: Chronic inflammation is a risk factor for colorectal cancer (CRC). Circulating C-reactive protein (CRP) is also moderately associated with CRC risk. However, observational studies are susceptible to unmeasured confounding or reverse causality. Using genetic risk variants as instrumental variables, we investigated the causal relationship between genetically elevated CRP concentration and CRC risk, using a Mendelian randomization approach. Methods: Individual-level data from 30 480 CRC cases and 22 844 controls from 33 participating studies in three international consortia were used: the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colorectal Transdisciplinary Study (CORECT) and the Colon Cancer Family Registry (CCFR). As instrumental variables, we included 19 single nucleotide polymorphisms (SNPs) previously associated with CRP concentration. The SNP-CRC associations were estimated using a logistic regression model adjusted for age, sex, principal components and genotyping phases. An inverse-variance weighted method was applied to estimate the causal effect of CRP on CRC risk. Results: Among the 19 CRP-associated SNPs, rs1260326 and rs6734238 were significantly associated with CRC risk (P = 7.5 × 10-4, and P = 0.003, respectively). A genetically predicted one-unit increase in the log-transformed CRP concentrations (mg/l) was not associated with increased risk of CRC [odds ratio (OR) = 1.04; 95% confidence interval (CI): 0.97, 1.12; P = 0.256). No evidence of association was observed in subgroup analyses stratified by other risk factors. Conclusions: In spite of adequate statistical power to detect moderate association, we found genetically elevated CRP concentration was not associated with increased risk of CRC among individuals of European ancestry. Our findings suggested that circulating CRP is unlikely to be a causal factor in CRC development.

18.
J Cancer Surviv ; 12(5): 679-690, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30097853

RESUMO

PURPOSE: Since physical activity (PA) has been shown to be associated with better prognosis and quality of life (QOL) in colorectal cancer (CRC) patients, this study focuses on the barriers of PA among CRC survivors. METHODS: This study is based on a population-based study from Germany of 1343 women and men, diagnosed with CRC between 2003 and 2008 and being alive five years later. Multivariable logistic regression was used to explore associations between baseline as well as five-year follow-up (5YFU) characteristics and physical inactivity (PIA) at 5YFU. Quartiles were calculated based on metabolic equivalent hours per week of PA at baseline and at 5YFU. Participants in quartile 1 were defined as physically inactive, and patients in quartile 2 to quartile 4 were defined as physically active. RESULTS: Cancer-specific factors such as having a stoma (odds ratio (OR) = 1.51, 95% confidence interval (CI) = 1.12-2.04), demographic factors such as living in a small town or city (OR = 1.46, 95% CI = 1.05-2.02; OR = 1.42, 95% CI = 1.01-2.02), older age (OR = 1.44, 95% CI = 0.80-2.58), or being divorced (OR = 1.72, 95% CI = 0.96-3.07), as well as lifestyle factors such as being a current smoker (OR = 1.54, 95% CI = 1.04-2.29) or being obese (OR = 1.43, 95% CI = 0.96-2.13) were associated with PIA at 5YFU. Subgroup analyses showed that the association between body mass index  and PIA was stronger in women than in men. Baseline PA was identified as a strong predictor of PIA at 5YFU. CONCLUSIONS: Findings suggest that predominately patients with a stoma, patients living in a more populated area, being older, divorced, a current smoker, or obese were more likely to be physically inactive and therefore could be targeted to be more physically active. IMPLICATIONS FOR CANCER SURVIVORS: Addressing barriers for PA might help to develop specific, individually tailored PA interventions to overcome PIA and improve the long-term outcome of CRC survivors.

19.
Health Qual Life Outcomes ; 16(1): 162, 2018 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-30086766

RESUMO

The original article [1] contains errors whereby some information provided in Tables 2 and 5 in the online version is missing in the PDF version; in addition, some details regarding the study by Mols et al., Johnstone et al. and Fransson et al. (2008) in Tables 1 and 5 require correction.

20.
Nat Genet ; 50(7): 968-978, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29915430

RESUMO

The breast cancer risk variants identified in genome-wide association studies explain only a small fraction of the familial relative risk, and the genes responsible for these associations remain largely unknown. To identify novel risk loci and likely causal genes, we performed a transcriptome-wide association study evaluating associations of genetically predicted gene expression with breast cancer risk in 122,977 cases and 105,974 controls of European ancestry. We used data from the Genotype-Tissue Expression Project to establish genetic models to predict gene expression in breast tissue and evaluated model performance using data from The Cancer Genome Atlas. Of the 8,597 genes evaluated, significant associations were identified for 48 at a Bonferroni-corrected threshold of P < 5.82 × 10-6, including 14 genes at loci not yet reported for breast cancer. We silenced 13 genes and showed an effect for 11 on cell proliferation and/or colony-forming efficiency. Our study provides new insights into breast cancer genetics and biology.

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