Publications by authors named "Volker Arndt"

192 Publications

Association of germline genetic variants with breast cancer-specific survival in patient subgroups defined by clinic-pathological variables related to tumor biology and type of systemic treatment.

Breast Cancer Res 2021 Aug 18;23(1):86. Epub 2021 Aug 18.

Department of Medicine, Huntsman Cancer Institute, Salt Lake City, UT, USA.

Background: Given the high heterogeneity among breast tumors, associations between common germline genetic variants and survival that may exist within specific subgroups could go undetected in an unstratified set of breast cancer patients.

Methods: We performed genome-wide association analyses within 15 subgroups of breast cancer patients based on prognostic factors, including hormone receptors, tumor grade, age, and type of systemic treatment. Analyses were based on 91,686 female patients of European ancestry from the Breast Cancer Association Consortium, including 7531 breast cancer-specific deaths over a median follow-up of 8.1 years. Cox regression was used to assess associations of common germline variants with 15-year and 5-year breast cancer-specific survival. We assessed the probability of these associations being true positives via the Bayesian false discovery probability (BFDP < 0.15).

Results: Evidence of associations with breast cancer-specific survival was observed in three patient subgroups, with variant rs5934618 in patients with grade 3 tumors (15-year-hazard ratio (HR) [95% confidence interval (CI)] 1.32 [1.20, 1.45], P = 1.4E-08, BFDP = 0.01, per G allele); variant rs4679741 in patients with ER-positive tumors treated with endocrine therapy (15-year-HR [95% CI] 1.18 [1.11, 1.26], P = 1.6E-07, BFDP = 0.09, per G allele); variants rs1106333 (15-year-HR [95% CI] 1.68 [1.39,2.03], P = 5.6E-08, BFDP = 0.12, per A allele) and rs78754389 (5-year-HR [95% CI] 1.79 [1.46,2.20], P = 1.7E-08, BFDP = 0.07, per A allele), in patients with ER-negative tumors treated with chemotherapy.

Conclusions: We found evidence of four loci associated with breast cancer-specific survival within three patient subgroups. There was limited evidence for the existence of associations in other patient subgroups. However, the power for many subgroups is limited due to the low number of events. Even so, our results suggest that the impact of common germline genetic variants on breast cancer-specific survival might be limited.
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http://dx.doi.org/10.1186/s13058-021-01450-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371820PMC
August 2021

Mendelian randomisation study of smoking exposure in relation to breast cancer risk.

Br J Cancer 2021 Aug 2. Epub 2021 Aug 2.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.

Background: Despite a modest association between tobacco smoking and breast cancer risk reported by recent epidemiological studies, it is still equivocal whether smoking is causally related to breast cancer risk.

Methods: We applied Mendelian randomisation (MR) to evaluate a potential causal effect of cigarette smoking on breast cancer risk. Both individual-level data as well as summary statistics for 164 single-nucleotide polymorphisms (SNPs) reported in genome-wide association studies of lifetime smoking index (LSI) or cigarette per day (CPD) were used to obtain MR effect estimates. Data from 108,420 invasive breast cancer cases and 87,681 controls were used for the LSI analysis and for the CPD analysis conducted among ever-smokers from 26,147 cancer cases and 26,072 controls. Sensitivity analyses were conducted to address pleiotropy.

Results: Genetically predicted LSI was associated with increased breast cancer risk (OR 1.18 per SD, 95% CI: 1.07-1.30, P = 0.11 × 10), but there was no evidence of association for genetically predicted CPD (OR 1.02, 95% CI: 0.78-1.19, P = 0.85). The sensitivity analyses yielded similar results and showed no strong evidence of pleiotropic effect.

Conclusion: Our MR study provides supportive evidence for a potential causal association with breast cancer risk for lifetime smoking exposure but not cigarettes per day among smokers.
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http://dx.doi.org/10.1038/s41416-021-01432-8DOI Listing
August 2021

Prevalence of benefit finding and posttraumatic growth in long-term cancer survivors: results from a multi-regional population-based survey in Germany.

Br J Cancer 2021 Sep 2;125(6):877-883. Epub 2021 Jul 2.

Unit of Cancer Survivorship, Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Background: Cancer studies reported mixed results on benefit finding (BF) and posttraumatic growth (PTG) prevalence and few were focused on long-term survivors.

Methods: BF and PTG were assessed in a multi-regional population-based study in Germany with 6952 breast, colorectal and prostate cancer survivors, using the Benefit Finding Scale and Posttraumatic Growth Inventory. We calculated the age-adjusted prevalence, stratified by demographical and clinical characteristics.

Results: Overall, 66.0% of cancer survivors indicated moderate-to-high BF, and 20.5% moderate-to-high PTG. Age-adjusted prevalence of BF and PTG differed according to cancer type (breast > colorectal > prostate) and sex (female > male). BF and PTG prevalence were higher in younger than in older respondents; the age-adjusted prevalence was higher in respondents who survived more years after diagnosis. The strength and direction of associations of age-adjusted prevalence with cancer stage, disease recurrence, and time since diagnosis varied according to cancer type and sex.

Conclusions: A substantial proportion of long-term cancer survivors reported moderate-to-high BF and PTG. However, the prevalence was lower in older and male cancer survivors, and during the earlier years after cancer diagnosis. Further longitudinal studies on PTG and BF in cancer survivors are warranted to address heterogeneity in survivors' experience after cancer diagnosis.
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http://dx.doi.org/10.1038/s41416-021-01473-zDOI Listing
September 2021

[Oral and pharyngeal cancer: incidence, mortality, and survival in Germany].

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2021 Aug 1;64(8):941-950. Epub 2021 Jul 1.

Epidemiologisches Krebsregister Baden-Württemberg, Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 581, 69120, Heidelberg, Deutschland.

Background: Lip, oral cavity, and pharynx cancers (ICD-10: C00-C14) describe a heterogeneous group of tumors with strong variations in incidence, mortality, and survival by entity.

Objectives: This work provides a detailed overview of epidemiologic measures for these tumor entities, taking into account heterogeneity in age, sex, location, and stage.

Material And Methods: Incidence and mortality data for Germany for the years 1999-2016 were extracted from the interactive database of the Center for Cancer Registry Data (ZfKD). Age and stage distributions and five-year relative survival were calculated on the pooled ZfKD data set (diagnosis years 1999-2017).

Results: In 2016, overall incidence and mortality for all entities were 17.6 and 7.0 per 100,000 men and 6.5 and 1.8 per 100,000 women, respectively. The five-year relative survival in 2015-2017 was 53 and 63%, respectively. There were marked differences in survival as well as age and stage distributions between entities. Trend analyses showed an increase in age at diagnosis, particularly in male patients, and no change in stage distributions. However, five-year relative survival increased from 45% (men) and 59% (women) in 1999-2002 to 52% and 63% in 2013-2017.

Conclusion: The marked heterogeneity of the studied tumors highlights the need to differentiate the analysis by sex and entity for meaningful interpretation of epidemiologic metrics. With the expansion of clinical cancer registration in Germany, additional analyses including other important clinical factors will be possible in the future.
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http://dx.doi.org/10.1007/s00103-021-03368-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316202PMC
August 2021

Health-Related Quality of Life in Very Long-Term Cancer Survivors 14-24 Years Post-Diagnosis Compared to Population Controls: A Population-Based Study.

Cancers (Basel) 2021 Jun 1;13(11). Epub 2021 Jun 1.

Unit of Cancer Survivorship, Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.

(1) Background: Little is known about the health-related quality of life (HRQoL) in very long-term cancer survivors (VLTCS) 10 and more years post-diagnosis. The objective was to compare cancer survivors' HRQoL 14-24 years post-diagnosis with that of same-aged non-cancer controls, stratified by age, sex, and disease status (disease-free vs. stage IV, recurrence, metastasis, or second cancer). (2) Methods: We recruited 2704 very long-term survivors of breast, colorectal and prostate cancer, and 1765 controls in German multi-regional population-based studies. The HRQoL was assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). Differences in the HRQoL were estimated with multiple regression, controlling for age, sex (where appropriate), and education. (3) Results: The overall global health status/quality of life of VLTCS more than a decade after diagnosis was slightly higher than that of population controls of the same age, but more symptoms and lower functioning were reported. Differences were small but statistically significant. Results differed by age, sex, and disease status. (4) Conclusions: The findings point out the need for a comprehensive survivorship care program in order to monitor and treat potential late and long-term effects after the diagnosis and treatment of cancer. Survivorship care should be risk-adapted to survivors' needs according to sociodemographic and clinical factors.
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http://dx.doi.org/10.3390/cancers13112754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199519PMC
June 2021

Distress mediates the relationship between cognitive appraisal of medical care and benefit finding/posttraumatic growth in long-term cancer survivors.

Cancer 2021 Oct 1;127(19):3680-3690. Epub 2021 Jul 1.

Unit of Cancer Survivorship, Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Background: The objective of this study was to ascertain long-term cancer survivors' (LTCS') appraisal of medical care and how these perceptions may influence their health and well-being, including benefit finding (BF) and posttraumatic growth (PTG).

Methods: In total, 6952 LTCS from a multiregional population-based study in Germany completed the Benefit Finding Scale, the Posttraumatic Growth Inventory, the Questionnaire on Stress in Cancer, and self-designed questions on cognitive appraisal of medical care. The authors explored the mediating role of distress between medical care appraisal and BF and PTG and the possible moderation of time since diagnosis in this relationship.

Results: LTCS' medical care appraisals ("no unresolved/untreated symptoms," "satisfaction with cancer care," and "satisfaction with care for other diseases") were positively associated with BF. PTG was positively associated with "no unresolved/untreated symptoms" and negatively associated with "satisfaction with care for other diseases." Cancer distress partially mediated the associations between appraisals of medical care and BF, between "no unresolved/untreated symptoms" and PTG and between "satisfaction with care for other diseases" and PTG; whereas it totally mediated the association between "satisfaction with cancer care" and PTG. Time was a significant moderator in the model; the negative indirect effect of cognitive appraisal on BF and PTG through cancer distress weakened with longer time since diagnosis.

Conclusions: Cancer survivors' medical care appraisal is associated with their perceptions of BF and PTG through distress. Therefore, distress screening could be part of the regular workup to identify distressed cancer survivors who are not satisfied with medical care; these survivors may benefit from interventions to reduce distress and increase BF and PTG.
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http://dx.doi.org/10.1002/cncr.33684DOI Listing
October 2021

Functional annotation of the 2q35 breast cancer risk locus implicates a structural variant in influencing activity of a long-range enhancer element.

Am J Hum Genet 2021 07 18;108(7):1190-1203. Epub 2021 Jun 18.

Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.

A combination of genetic and functional approaches has identified three independent breast cancer risk loci at 2q35. A recent fine-scale mapping analysis to refine these associations resulted in 1 (signal 1), 5 (signal 2), and 42 (signal 3) credible causal variants at these loci. We used publicly available in silico DNase I and ChIP-seq data with in vitro reporter gene and CRISPR assays to annotate signals 2 and 3. We identified putative regulatory elements that enhanced cell-type-specific transcription from the IGFBP5 promoter at both signals (30- to 40-fold increased expression by the putative regulatory element at signal 2, 2- to 3-fold by the putative regulatory element at signal 3). We further identified one of the five credible causal variants at signal 2, a 1.4 kb deletion (esv3594306), as the likely causal variant; the deletion allele of this variant was associated with an average additional increase in IGFBP5 expression of 1.3-fold (MCF-7) and 2.2-fold (T-47D). We propose a model in which the deletion allele of esv3594306 juxtaposes two transcription factor binding regions (annotated by estrogen receptor alpha ChIP-seq peaks) to generate a single extended regulatory element. This regulatory element increases cell-type-specific expression of the tumor suppressor gene IGFBP5 and, thereby, reduces risk of estrogen receptor-positive breast cancer (odds ratio = 0.77, 95% CI 0.74-0.81, p = 3.1 × 10).
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http://dx.doi.org/10.1016/j.ajhg.2021.05.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322933PMC
July 2021

Inpatient rehabilitation therapy among colorectal cancer patients - utilization and association with prognosis: a cohort study.

Acta Oncol 2021 Aug 17;60(8):1000-1010. Epub 2021 Jun 17.

Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.

Background: Inpatient rehabilitation therapy (IRT) is commonly offered to cancer patients during or after cancer treatment in Germany. However, little is known about utilization and long-term effects of this offer in colorectal cancer (CRC) patients. We aimed to assess IRT utilization, determinants of utilization and the association between IRT and survival in CRC patients.

Materials And Methods: CRC patients diagnosed in 2005-2014 recruited in the population-based DACHS study in South West Germany were included. Determinants of IRT utilization were assessed by multivariable logistic regression. Hazard ratios (HRs) of the association of IRT with overall and disease-specific survival were estimated by adjusted Cox proportional hazards models. Modified landmark approach was applied to avoid immortal time biased results.

Results: Among the included CRC patients ( = 3704), 43.6% underwent IRT. Patients who did not live in a relationship with a partner, worked as employee and who reported higher levels of physical activity were more likely to undergo IRT. Patients were less likely to undergo IRT if they had private health insurance, were diagnosed with cancer stage IV, received no or laparoscopic cancer surgery or were treated in a hospital with medium vs. high surgical volume. The median follow-up time was 4.4 years (post-landmark). Utilization of IRT was associated with better overall (HR 0.81, 95% confidence interval 0.72-0.92) and disease-specific survival (HR 0.72, 95% confidence interval 0.61-0.85).

Conclusion: Almost every other CRC patient underwent IRT. Next to clinical characteristics, identified social and lifestyle characteristics seemed to play an essential role in the decision-making. Use of IRT was associated with better overall and disease-specific survival.
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http://dx.doi.org/10.1080/0284186X.2021.1940274DOI Listing
August 2021

Gene-Environment Interactions Relevant to Estrogen and Risk of Breast Cancer: Can Gene-Environment Interactions Be Detected Only among Candidate SNPs from Genome-Wide Association Studies?

Cancers (Basel) 2021 May 14;13(10). Epub 2021 May 14.

Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, 2730 Herlev, Denmark.

In this study we aim to examine gene-environment interactions (GxEs) between genes involved with estrogen metabolism and environmental factors related to estrogen exposure. GxE analyses were conducted with 1970 Korean breast cancer cases and 2052 controls in the case-control study, the Seoul Breast Cancer Study (SEBCS). A total of 11,555 SNPs from the 137 candidate genes were included in the GxE analyses with eight established environmental factors. A replication test was conducted by using an independent population from the Breast Cancer Association Consortium (BCAC), with 62,485 Europeans and 9047 Asians. The GxE tests were performed by using two-step methods in GxEScan software. Two interactions were found in the SEBCS. The first interaction was shown between rs13035764 of NCOA1 and age at menarche in the GE|2df model (-2df = 1.2 × 10). The age at menarche before 14 years old was associated with the high risk of breast cancer, and the risk was higher when subjects had homozygous minor allele G. The second GxE was shown between rs851998 near ESR1 and height in the GE|2df model (-2df = 1.1 × 10). Height taller than 160 cm was associated with a high risk of breast cancer, and the risk increased when the minor allele was added. The findings were not replicated in the BCAC. These results would suggest specificity in Koreans for breast cancer risk.
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http://dx.doi.org/10.3390/cancers13102370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156547PMC
May 2021

Correction to: Association of laparoscopic colectomy versus open colectomy on the long‑term health‑related quality of life of colon cancer survivors.

Surg Endosc 2021 Aug;35(8):4900

Unit of Cancer Survivorship, Division of Clinical, Epidemiology and Aging Research, German Cancer Research Center (DKFZ), P.O. Box 101949, 69009, Heidelberg, Germany.

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http://dx.doi.org/10.1007/s00464-021-08557-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263454PMC
August 2021

Identifying classes of the pain, fatigue, and depression symptom cluster in long-term prostate cancer survivors-results from the multi-regional Prostate Cancer Survivorship Study in Switzerland (PROCAS).

Support Care Cancer 2021 Apr 13. Epub 2021 Apr 13.

National Institute for Cancer Epidemiology and Registration (NICER), c/o University of Zurich, Zurich, Switzerland.

Purpose: Aside from urological and sexual problems, long-term (≥5 years after initial diagnosis) prostate cancer (PC) survivors might suffer from pain, fatigue, and depression. These concurrent symptoms can form a cluster. In this study, we aimed to investigate classes of this symptom cluster in long-term PC survivors, to classify PC survivors accordingly, and to explore associations between classes of this cluster and health-related quality of life (HRQoL).

Methods: Six hundred fifty-three stage T1-T3N0M0 survivors were identified from the Prostate Cancer Survivorship in Switzerland (PROCAS) study. Fatigue was assessed with the EORTC QLQ-FA12, depressive symptoms with the MHI-5, and pain with the EORTC QLQ-C30 questionnaire. Latent class analysis was used to derive cluster classes. Factors associated with the derived classes were determined using multinomial logistic regression analysis.

Results: Three classes were identified: class 1 (61.4%) - "low pain, low physical and emotional fatigue, moderate depressive symptoms"; class 2 (15.1%) - "low physical fatigue and pain, moderate emotional fatigue, high depressive symptoms"; class 3 (23.5%) - high scores for all symptoms. Survivors in classes 2 and 3 were more likely to be physically inactive, report a history of depression or some other specific comorbidity, be treated with radiation therapy, and have worse HRQoL outcomes compared to class 1.

Conclusion: Three distinct classes of the pain, fatigue, and depression cluster were identified, which are associated with treatment, comorbidities, lifestyle factors, and HRQoL outcomes. Improving classification of PC survivors according to severity of multiple symptoms could assist in developing interventions tailored to survivors' needs.
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http://dx.doi.org/10.1007/s00520-021-06132-wDOI Listing
April 2021

Trends of incidence, mortality and survival for chronic lymphocytic leukaemia / small lymphocytic lymphoma in Switzerland between 1997 and 2016: a population-based study.

Swiss Med Wkly 2021 Mar 15;151:w20463. Epub 2021 Mar 15.

Foundation National Institute for Cancer Epidemiology and Registration (NICER), c/o University of Zurich, Switzerland / Unit of Cancer Survivorship, Division of Clinical Epidemiology and Aging Research, German Cancer Research Centre (DKFZ), Heidelberg, Germany.

Background: During the last 20 years, treatment for chronic lymphocytic leukaemia (CLL) / small lymphocytic lymphoma (SLL) has advanced, with improved clinical outcomes in randomised controlled trials. Currently, no data have been published from Switzerland to assess effectiveness of recent healthcare advances in CLL/SLL on a population-based level. We aimed to estimate trends in incidence, mortality and survival for patients with CLL/SLL in Switzerland.

Methods: We retrospectively studied registry data from the National Agency for Cancer Registration (NACR) database in Switzerland from 1997 to 2016. We investigated incidence, mortality and survival in consecutive 5-year periods. Age-specific rates were calculated for three age groups (<65 years, 65–74 years and ≥75 years).

Results: We obtained 6301 cases with CLL/SLL. Median age at diagnosis was 72 years. From 7.0 per 100,000 person-years in 1997–2002, age-adjusted incidence rates peaked at 7.8 per 100,000 person-years in the second time period, 2002–2006, and declined afterwards to 6.4 per 100,000 person-years in 2012–2016. Mortality declined from 2.4 per 100,000 person-years in 1997–2002 to 2.0 per 100,000 in 2012–2016. Five- and 10-year age-standardised relative survival increased from 77.9% and 55.6%, respectively, in 1997–2001 to 83.6% (p = 0.009) and 64.2% (p = 0.005), respectively, in 2012–2016. Improvement in age-specific relative survival was only significant in the middle age group (65–74 years). Incidence and mortality were significantly higher in males. Females had better relative survival.

Conclusion: We found no clear down- or upward trend in age-adjusted incidence rates. Age-standardised survival improved over time, mainly in the two younger age-groups, but this improvement was statistically significant in those aged 65–74 years only. Males have higher incidence rates, higher mortality and shorter survival than females. Reporting delay and underreporting are major limitations in the interpretation of registry data from patients diagnosed with CLL/SLL.
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http://dx.doi.org/10.4414/smw.2021.20463DOI Listing
March 2021

Genetically predicted circulating concentrations of micronutrients and risk of colorectal cancer among individuals of European descent: a Mendelian randomization study.

Am J Clin Nutr 2021 06;113(6):1490-1502

Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Background: The literature on associations of circulating concentrations of minerals and vitamins with risk of colorectal cancer is limited and inconsistent. Evidence from randomized controlled trials (RCTs) to support the efficacy of dietary modification or nutrient supplementation for colorectal cancer prevention is also limited.

Objectives: To complement observational and RCT findings, we investigated associations of genetically predicted concentrations of 11 micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B-6, vitamin B-12, and zinc) with colorectal cancer risk using Mendelian randomization (MR).

Methods: Two-sample MR was conducted using 58,221 individuals with colorectal cancer and 67,694 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. Inverse variance-weighted MR analyses were performed with sensitivity analyses to assess the impact of potential violations of MR assumptions.

Results: Nominally significant associations were noted for genetically predicted iron concentration and higher risk of colon cancer [ORs per SD (ORSD): 1.08; 95% CI: 1.00, 1.17; P value = 0.05] and similarly for proximal colon cancer, and for vitamin B-12 concentration and higher risk of colorectal cancer (ORSD: 1.12; 95% CI: 1.03, 1.21; P value = 0.01) and similarly for colon cancer. A nominally significant association was also noted for genetically predicted selenium concentration and lower risk of colon cancer (ORSD: 0.98; 95% CI: 0.96, 1.00; P value = 0.05) and similarly for distal colon cancer. These associations were robust to sensitivity analyses. Nominally significant inverse associations were observed for zinc and risk of colorectal and distal colon cancers, but sensitivity analyses could not be performed. None of these findings survived correction for multiple testing. Genetically predicted concentrations of β-carotene, calcium, copper, folate, magnesium, phosphorus, and vitamin B-6 were not associated with disease risk.

Conclusions: These results suggest possible causal associations of circulating iron and vitamin B-12 (positively) and selenium (inversely) with risk of colon cancer.
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http://dx.doi.org/10.1093/ajcn/nqab003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168352PMC
June 2021

Genetic architectures of proximal and distal colorectal cancer are partly distinct.

Gut 2021 Jul 25;70(7):1325-1334. Epub 2021 Feb 25.

Cancer Prevention and Control Program, Catalan Institute of Oncology - IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.

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) 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.
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http://dx.doi.org/10.1136/gutjnl-2020-321534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223655PMC
July 2021

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers.

Nat Commun 2021 02 17;12(1):1078. Epub 2021 Feb 17.

Copenhagen General Population Study, Herlev and Gentofte Hospital Copenhagen University Hospital, Herlev, Denmark.

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, 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.
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http://dx.doi.org/10.1038/s41467-020-20496-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890067PMC
February 2021

Breast Cancer Risk Factors and Survival by Tumor Subtype: Pooled Analyses from the Breast Cancer Association Consortium.

Cancer Epidemiol Biomarkers Prev 2021 04 26;30(4):623-642. Epub 2021 Jan 26.

Gynaecology Research Unit, Hannover Medical School, Hannover, Germany.

Background: It is not known whether 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 ( > 0.30). The strongest associations were between all-cause mortality and BMI ≥30 versus 18.5-25 kg/m [HR (95% confidence interval (CI), 1.19 (1.06-1.34)]; current versus never smoking [1.37 (1.27-1.47)], high versus low physical activity [0.43 (0.21-0.86)], age ≥30 years versus <20 years at first pregnancy [0.79 (0.72-0.86)]; >0-<5 years versus ≥10 years since last full-term birth [1.31 (1.11-1.55)]; ever versus never use of oral contraceptives [0.91 (0.87-0.96)]; ever versus 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; for example, 1.11 (1.02-1.21) for current versus 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.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026532PMC
April 2021

CYP3A7*1C allele: linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers.

Br J Cancer 2021 02 26;124(4):842-854. Epub 2021 Jan 26.

Molecular Epidemiology Group, C080, German Cancer Research Center (DKFZ), Heidelberg, Germany.

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); 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).

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.
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http://dx.doi.org/10.1038/s41416-020-01185-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884683PMC
February 2021

Estimation of the Potentially Avoidable Excess Deaths Associated with Socioeconomic Inequalities in Cancer Survival in Germany.

Cancers (Basel) 2021 Jan 19;13(2). Epub 2021 Jan 19.

Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.

Many countries have reported survival inequalities due to regional socioeconomic deprivation. To quantify the potential gain from eliminating cancer survival disadvantages associated with area-based deprivation in Germany, we calculated the number of avoidable excess deaths. We used population-based cancer registry data from 11 of 16 German federal states. Patients aged ≥15 years diagnosed with an invasive malignant tumor between 2008 and 2017 were included. Area-based socioeconomic deprivation was assessed using the quintiles of the German Index of Multiple Deprivation (GIMD) 2010 on a municipality level nationwide. Five-year age-standardized relative survival for 25 most common cancer sites and for total cancer were calculated using period analysis. Incidence and number of avoidable excess deaths in Germany in 2013-2016 were estimated. Summed over the 25 cancer sites, 4100 annual excess deaths (3.0% of all excess deaths) could have been avoided each year in Germany during the period 2013-2016 if relative survival were in all regions comparable with the least deprived regions. Colorectal, oral and pharynx, prostate, and bladder cancer contributed the largest numbers of avoidable excess deaths. Our results provide a good basis to estimate the potential of intervention programs for reducing socioeconomic inequalities in cancer burden in Germany.
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http://dx.doi.org/10.3390/cancers13020357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835812PMC
January 2021

Age-specific prevalence and determinants of depression in long-term breast cancer survivors compared to female population controls.

Cancer Med 2020 11 6;9(22):8713-8721. Epub 2020 Oct 6.

Unit of Cancer Survivorship, Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.

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.
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http://dx.doi.org/10.1002/cam4.3476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666751PMC
November 2020

Prevalence and severity of long-term physical, emotional, and cognitive fatigue across 15 different cancer entities.

Cancer Med 2020 11 7;9(21):8053-8061. Epub 2020 Sep 7.

Division of Physical Activity, Prevention and Cancer, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), Heidelberg, Germany.

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.
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http://dx.doi.org/10.1002/cam4.3413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643651PMC
November 2020

Genome-wide Modeling of Polygenic Risk Score in Colorectal Cancer Risk.

Am J Hum Genet 2020 09 5;107(3):432-444. Epub 2020 Aug 5.

School of Public Health, Imperial College London, London SW7 2AZ, UK.

Accurate colorectal cancer (CRC) risk prediction models are critical for identifying individuals at low and high risk of developing CRC, as they can then be offered targeted screening and interventions to address their risks of developing disease (if they are in a high-risk group) and avoid unnecessary screening and interventions (if they are in a low-risk group). As it is likely that thousands of genetic variants contribute to CRC risk, it is clinically important to investigate whether these genetic variants can be used jointly for CRC risk prediction. In this paper, we derived and compared different approaches to generating predictive polygenic risk scores (PRS) from genome-wide association studies (GWASs) including 55,105 CRC-affected case subjects and 65,079 control subjects of European ancestry. We built the PRS in three ways, using (1) 140 previously identified and validated CRC loci; (2) SNP selection based on linkage disequilibrium (LD) clumping followed by machine-learning approaches; and (3) LDpred, a Bayesian approach for genome-wide risk prediction. We tested the PRS in an independent cohort of 101,987 individuals with 1,699 CRC-affected case subjects. The discriminatory accuracy, calculated by the age- and sex-adjusted area under the receiver operating characteristics curve (AUC), was highest for the LDpred-derived PRS (AUC = 0.654) including nearly 1.2 M genetic variants (the proportion of causal genetic variants for CRC assumed to be 0.003), whereas the PRS of the 140 known variants identified from GWASs had the lowest AUC (AUC = 0.629). Based on the LDpred-derived PRS, we are able to identify 30% of individuals without a family history as having risk for CRC similar to those with a family history of CRC, whereas the PRS based on known GWAS variants identified only top 10% as having a similar relative risk. About 90% of these individuals have no family history and would have been considered average risk under current screening guidelines, but might benefit from earlier screening. The developed PRS offers a way for risk-stratified CRC screening and other targeted interventions.
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http://dx.doi.org/10.1016/j.ajhg.2020.07.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477007PMC
September 2020

The relationship between posttraumatic growth and health-related quality of life in adult cancer survivors: A systematic review.

J Affect Disord 2020 11 18;276:159-168. Epub 2020 Jul 18.

Unit of Cancer Survivorship, Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), P.O. Box 101949, 69009 Heidelberg, Germany. Electronic address:

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 (I=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.
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http://dx.doi.org/10.1016/j.jad.2020.07.044DOI Listing
November 2020

Germline HOXB13 mutations p.G84E and p.R217C do not confer an increased breast cancer risk.

Sci Rep 2020 06 16;10(1):9688. Epub 2020 Jun 16.

Department of Gynecology and Obstetrics, University of Tübingen, Tübingen, Germany.

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.
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http://dx.doi.org/10.1038/s41598-020-65665-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7297796PMC
June 2020

Health-related quality of life in long-term prostate cancer survivors after nerve-sparing and non-nerve-sparing radical prostatectomy-Results from the multiregional PROCAS study.

Cancer Med 2020 08 10;9(15):5416-5424. Epub 2020 Jun 10.

National Institute for Cancer Epidemiology and Registration (NICER), c/o University of Zurich, Zurich, Switzerland.

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.
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http://dx.doi.org/10.1002/cam4.3197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402816PMC
August 2020

Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses.

Nat Genet 2020 06 18;52(6):572-581. Epub 2020 May 18.

Molecular Medicine Unit, Fundación Pública Galega de Medicina Xenómica, Santiago de Compostela, Spain.

Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype. 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), 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.
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http://dx.doi.org/10.1038/s41588-020-0609-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808397PMC
June 2020

Physical activity and long-term fatigue among colorectal cancer survivors - a population-based prospective study.

BMC Cancer 2020 May 18;20(1):438. Epub 2020 May 18.

Unit of Cancer Survivorship, Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120, Heidelberg, Germany.

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.
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http://dx.doi.org/10.1186/s12885-020-06918-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236466PMC
May 2020

Combined Associations of a Polygenic Risk Score and Classical Risk Factors With Breast Cancer Risk.

J Natl Cancer Inst 2021 03;113(3):329-337

Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.

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.
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http://dx.doi.org/10.1093/jnci/djaa056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936056PMC
March 2021

Physical Activity and Long-term Quality of Life among Colorectal Cancer Survivors-A Population-based Prospective Study.

Cancer Prev Res (Phila) 2020 07 6;13(7):611-622. Epub 2020 Apr 6.

Unit of Cancer Survivorship, Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.

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(β) = -2.52, 95% confidence interval (CI) = -3.77, -1.27; β = -1.92, CI = -3.17, -0.67) and emotional functioning (β = -2.52, CI = -3.84, -1.19; β = -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.
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http://dx.doi.org/10.1158/1940-6207.CAPR-19-0377DOI Listing
July 2020
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