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  • 1
    Language: English
    In: The American journal of clinical nutrition, 2016-06, Vol.103 (6), p.1497-1506
    Description: Studies on the association between alcohol consumption and colorectal cancer (CRC) prognosis have yielded inconsistent results. The associations of lifetime and 1-y prediagnostic alcohol consumption with relevant prognostic outcomes were evaluated in a large population-based cohort of CRC patients. In 2003-2010, 3121 patients diagnosed with CRC were interviewed on sociodemographic and lifestyle factors, medication, and comorbidities. Cancer recurrence, vital status, and cause of death were documented for a median follow-up time of 4.8 y. With the use of Cox proportional hazard regression, associations between lifetime and recent alcohol consumption and overall, CRC-specific, recurrence-free, and disease-free survival were analyzed. In this patient cohort with a median age of 69 y at diagnosis, lifetime abstainers showed poorer overall [adjusted HR (aHR): 1.25; 95% CI: 1.03, 1.52] and CRC-specific (aHR: 1.37; 95% CI: 1.10, 1.70) survival than lifetime light drinkers (women: 〉0-12 g/d; men: 〉0-24 g/d). Lifetime heavy drinkers showed poorer overall (aHR: 1.37; 95% CI: 1.06, 1.78) and disease-free (aHR: 1.38; 95% CI: 1.09, 1.74) survival. Alcohol abstaining in the year before diagnosis was associated with poorer overall (aHR: 1.42; 95% CI: 1.20, 1.68), CRC-specific (aHR: 1.38; 95% CI: 1.13, 1.68), and disease-free (aHR: 1.23; 95% CI: 1.05, 1.44) survival. Lifetime abstainers with nonmetastatic disease showed poorer CRC-specific (aHR: 1.48; 95% CI: 1.10, 2.00) and recurrence-free (aHR: 1.32; 95% CI: 1.02, 1.70) survival. Wine abstaining but not beer or liquor abstaining was associated with poorer survival. Associations between alcohol consumption and prognosis varied according to presence of diabetes and age. Prediagnostic alcohol abstaining and heavy drinking were associated with poorer survival after a CRC diagnosis than light drinking. The protective effects of light consumption might be restricted to wine, and associations might differ according to age and presence of diabetes mellitus.
    Subject(s): Colorectal Neoplasms - mortality ; Wine ; Prognosis ; Humans ; Middle Aged ; Risk Factors ; Proportional Hazards Models ; Male ; Survival Rate ; Alcohol Abstinence ; Alcoholic Beverages ; Alcohol Drinking - adverse effects ; Beer ; Disease-Free Survival ; Aged, 80 and over ; Adult ; Female ; Aged ; Neoplasm Recurrence, Local - epidemiology ; Germany ; Cancer patients ; Drinking of alcoholic beverages ; Analysis ; Patient outcomes ; Colorectal cancer ; Alcohol use ; Index Medicus ; Abridged Index Medicus
    ISSN: 0002-9165
    E-ISSN: 1938-3207
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 2
    Language: English
    In: The American journal of clinical nutrition, 2016-10-01, Vol.104 (4), p.1110-1120
    Description: ABSTRACT Background: Studies on the association between body mass index (BMI) and colorectal cancer (CRC) prognosis after diagnosis have yielded inconsistent results. Few studies have investigated associations between prediagnostic BMI change and CRC prognosis. Objective: The associations of BMI at diagnosis and prediagnostic BMI change with relevant prognostic outcomes were evaluated in a large population-based cohort of CRC patients. Design: A total of 3130 patients diagnosed with CRC between 2003 and 2010 were interviewed on sociodemographic and lifestyle factors, medication, and comorbidities. Cancer recurrence, vital status, and cause of death were documented for a median follow-up time of 4.9 y. With the use of Cox proportional hazards regression, associations between BMI at diagnosis and BMI change (difference between 1–10 y before diagnosis and at diagnosis) and overall, CRC-specific, recurrence-free, and disease-free survival were analyzed. Results: Compared with normal weight, overweight [BMI (in kg/m2): 25 to 〈30] and obesity (BMI: ≥30) were associated with improved overall [adjusted HR (aHR): 0.82; 95% CI: 0.70, 0.95 and aHR: 0.80; 95% CI: 0.66, 0.98, respectively] and CRC-specific (aHR: 0.84; 95% CI: 0.71, 1.01 and aHR: 0.78; 95% CI: 0.62, 0.99, respectively) survival, with associations being even stronger when the analysis was restricted to nonmetastatic disease. Compared with stable BMI, a strong prediagnostic BMI decrease of 〉5 was associated with poorer prognosis for all survival outcomes (overall survival—aHR: 1.83; 95% CI: 1.43, 2.34; CRC-specific survival—aHR: 1.78; 95% CI: 1.33, 2.39), and associations were particularly pronounced in men (overall survival—aHR: 2.31; 95% CI: 1.65, 3.22; CRC-specific survival—aHR: 2.56; 95% CI: 1.72, 3.81; P-interaction = 0.08). Conclusions: Overweight and obesity are associated with enhanced survival after a CRC diagnosis. A major decrease in BMI in the years before diagnosis is a strong independent predictor of decreased survival. This trial was registered at www.studybox.de as ST-D066.
    Subject(s): Body Mass Index ; Colorectal Neoplasms - mortality ; Obesity ; Recurrence ; Prognosis ; Humans ; Middle Aged ; Proportional Hazards Models ; Male ; Colorectal Neoplasms - diagnosis ; Overweight ; Weight Loss ; Aged, 80 and over ; Adult ; Female ; Aged ; Colorectal Neoplasms - complications ; Cohort Studies ; Cancer patients ; Care and treatment ; Body weight ; Analysis ; Colorectal cancer ; Weight loss ; Health aspects ; Risk factors ; Index Medicus ; Abridged Index Medicus
    ISSN: 0002-9165
    E-ISSN: 1938-3207
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 3
    Language: English
    In: British journal of cancer, 2016-11-22, Vol.115 (11), p.1359-1366
    Description: Previous studies have shown adverse effects of CpG island methylator phenotype (CIMP) on colorectal cancer (CRC) prognosis. However, sample sizes were often limited and only few studies were able to adjust for relevant molecular features associated with CIMP. The aim of this study was to investigate the impact of CIMP on CRC survival in a large population-based study with comprehensive adjustment. The CIMP status and other molecular tumour features were analysed in 1385 CRC patients diagnosed between 2003 and 2010. Detailed information were obtained from standardised personal interviews and medical records. During follow-up (median: 4.9 years), we assessed vital status, cause of death and therapy details. Cox proportional hazard regression models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of survival after CRC. The CIMP-H occurred more frequently in patients with older age, female gender, cancer in the proximal colon, BRAF mutation and microsatellite instability-high (MSI-H). However, CIMP status was not associated with CRC prognosis in CRC patients (HR=1.00; 95% CI=0.72-1.40 for overall survival; HR=0.96; 95% CI=0.65-1.41 for disease-specific survival) or in any of the subgroups. Although CIMP status was associated with the presence of MSI-H and BRAF mutation, the prognostic effects of MSI-H (HR=0.49; 95% CI=0.27-0.90) and BRAF mutation (HR=1.78; 95% CI=1.10-2.84) were independent of CIMP status. Similar benefit of chemotherapy was found for CRC outcomes in both the CIMP-low/negative group and the CIMP-high group. CpG island methylator phenotype was not associated with CRC prognosis after adjusting for other important clinical factors and associated mutations.
    Subject(s): Colorectal Neoplasms - genetics ; Humans ; Middle Aged ; Male ; Antineoplastic Agents - therapeutic use ; DNA Methylation ; Phenotype ; Colorectal Neoplasms - drug therapy ; Survival Analysis ; CpG Islands ; Female ; Aged ; Colorectal Neoplasms - pathology ; Index Medicus ; colorectal cancer ; Molecular Diagnostics ; subtype ; CRC ; molecular pathological epidemiology ; DNA methylation ; malignant ; prognosis
    ISSN: 0007-0920
    E-ISSN: 1532-1827
    Source: Nature Open Access
    Source: Nature Journals Online
    Source: PubMed Central
    Source: Alma/SFX Local Collection
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  • 4
    Language: English
    In: British journal of cancer, 2020-05, Vol.122 (11), p.1604-1610
    Description: Smoking and alcohol increase risk for colorectal malignancies. However, colorectal cancer (CRC) is a heterogenic disease and associations with the molecular pathological pathways are unclear. This population-based case-control study includes 2444 cases with first-diagnosis CRC and 2475 controls. Tumour tissue was analysed for MSI (microsatellite instability), CIMP (CpG island methylator phenotype), BRAF (B-Raf proto-oncogene serine/threonine kinase gene) and KRAS (Kirsten rat sarcoma viral oncogene homologue gene) mutations. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated for associations between alcohol and smoking and CRC molecular subtypes and pathways. Current smoking showed higher ORs for MSI-high (OR = 2.79, 95% CI: 1.86-4.18) compared to MSS (OR = 1.41, 1.14-1.75, p-heterogeneity (p-het) = 0.001), BRAF-mutated (mut) (OR = 2.40, 1.41-4.07) compared to BRAF-wild type (wt) (OR = 1.52, 1.24-1.88, p-het = 0.074), KRAS-wt (OR = 1.70, 1.36-2.13) compared to KRAS-mut (OR = 1.26, 0.95-1.68, p-het = 0.039) and CIMP-high (OR = 2.01, 1.40-2.88) compared to CIMP-low/negative CRC (OR = 1.50, 1.22-1.85, p-het=0.101). Current smoking seemed more strongly associated with sessile serrated pathway (CIMP-high + BRAF-mut; OR = 2.39, 1.27-4.52) than with traditional pathway CRC (MSS + CIMP-low/negative + BRAF-wt; OR = 1.50, 1.16-1.94) and no association was observed with alternate pathway CRC (MSS + CIMP-low/negative + KRAS-wt; OR = 1.08, 0.77-1.43). No heterogeneity was observed in alcohol consumption association by molecular subtypes. In this large case-control study, smoking was more strongly associated with MSI-high and KRAS-wt CRC and with cases showing features of the sessile serrated pathway. Association patterns were less clear for alcohol consumption.
    Subject(s): Smoking - adverse effects ; Colorectal Neoplasms - genetics ; Humans ; Middle Aged ; Risk Factors ; Male ; Alcohol Drinking - adverse effects ; Case-Control Studies ; Aged, 80 and over ; Adult ; Female ; Aged ; Colorectal Neoplasms - pathology ; Index Medicus ; Risk factors ; Cancer epidemiology
    ISSN: 0007-0920
    E-ISSN: 1532-1827
    Source: Nature Open Access
    Source: Nature Journals Online
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 5
    Language: English
    In: Modern pathology, 2012-02, Vol.25 (2), p.308-315
    Description: Renal cell carcinomas associated with Xp11.2 translocations have recently been identified as a distinct biological entity. The translocation results in the fusion of the transcription factor TFE3 to one of several different fusion partners including PRCC, PSF, NONO, ASPL or CTLC with consecutive overexpression of the chimeric protein. As the true frequency of these neoplasms as well as the biological properties of TFE3 activation in renal cell carcinomas are largely unknown, we have examined TFE3 expression as well as the underlying genetic alterations in a large, hospital-based series of renal cell carcinomas with long-term follow-up information. Out of a total of 876 tumours, TFE3 translocations were detected in five cases (0.6%). Three additional cases were identified in a second series of cases comprising of renal cell carcinomas developing in patients before the age of 50. However, using immunohistochemistry, 9% of all renal cell carcinomas showed some degree of TFE3 reactivity. Interestingly, these cases were associated with high nuclear grade, greater tumour extent and metastatic disease as well as an unfavourable patient outcome on uni- and multivariate analysis. Fluorescence in situ hybridisation (FISH) revealed TFE3 amplifications as an additional, novel mechanism leading to increased TFE3 expression levels. In conclusion, our data show that Xp11 translocation renal cell carcinomas are uncommon tumours accounting for 〈1% of adult renal cell carcinomas and that the diagnosis of Xp11 translocation renal cell carcinomas needs to be verified using molecular techniques. In turn, TFE3 overexpressing tumours show an aggressive behaviour and Xp11 translocation is only one of several possible underlying genomic alterations.
    Subject(s): Translocation, Genetic ; Kidney Neoplasms - genetics ; Prognosis ; Tissue Array Analysis ; Humans ; Middle Aged ; Carcinoma, Renal Cell - genetics ; Male ; Kidney Neoplasms - metabolism ; Young Adult ; Neoplasm Grading ; Aged, 80 and over ; Adult ; Female ; Carcinoma, Renal Cell - pathology ; Kaplan-Meier Estimate ; Proportional Hazards Models ; Reverse Transcriptase Polymerase Chain Reaction ; Carcinoma, Renal Cell - metabolism ; Adolescent ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - genetics ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - metabolism ; Kidney Neoplasms - pathology ; Aged ; Neoplasm Staging ; Index Medicus
    ISSN: 0893-3952
    E-ISSN: 1530-0285
    Source: Nature Open Access
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 6
    Language: English
    In: BJU international, 2013-12, Vol.112 (8), p.1080-1087
    Description: Objectives To evaluate the Prostate Imaging Reporting and Data System (PIRADS) in multiparametric magnetic resonance imaging (mpMRI) based on single cores and single‐core histology. To calculate positive (PPV) and negative predictive values (NPV) of different modalities of mpMRI. Patients and Methods We performed MRI‐targeted transrectal ultrasound‐guided perineal prostate biopsies on 50 patients (mean age 66 years, mean PSA level of 9.9 ng/mL) with suspicion of prostate cancer. The biopsy trajectories of every core taken were documented in three dimensions (3D) in a 3D‐prostate model. Every core was evaluated separately for prostate cancer and the performed biopsy trajectories were projected on mpMRI images. PIRADS scores of 1177 cores were then assessed by a histology ‘blinded’ uro‐radiologist in T2‐weighted (T2W), dynamic contrast‐enhanced (DCE), diffusion‐weighted imaging (DWI) and magnetic resonance spectroscopy (MRS). Results The PIRADS score was significantly higher in cores positive for cancer than in negative cores. There was a significant correlation between the PIRADS score and histopathology for every modality. Receiver operating characteristic (ROC) analysis showed excellent specificity for T2W (90% peripheral zone/97% transition zone) and DWI (98%/97%) images regardless of the prostate region observed. These numbers decreased for DCE (80%/93%) and MRS (76%/83%). All modalities had NPVs of 99%, if a PIRADS score threshold of 2 (for T2W, DCE, and MRS) or 3 (for DWI) was used. However, PPVs were low. Conclusions Our results show that PIRADS scoring is feasible for clinical routine and allows standardised reporting. PIRADS can be used as a decision‐support system for targeting of suspicious lesions. mpMRI has a high NPV for prostate cancer and, thus, might be a valuable tool in the initial diagnostic evaluation.
    Subject(s): biopsy ; prostate ; PIRADS‐score ; hybrid imaging ; mpMRI ; Gynecology. Andrology. Obstetrics ; Radiodiagnosis. Nmr imagery. Nmr spectrometry ; Investigative techniques, diagnostic techniques (general aspects) ; Biological and medical sciences ; Genital system. Mammary gland ; Medical sciences ; Male genital diseases ; Tumors ; Perineum - pathology ; Predictive Value of Tests ; Prostatic Neoplasms - pathology ; Reproducibility of Results ; Magnetic Resonance Spectroscopy ; Prostatic Neoplasms - surgery ; Rectum - pathology ; Humans ; Middle Aged ; Decision Support Techniques ; Male ; Feasibility Studies ; Prostate - pathology ; Sensitivity and Specificity ; Diffusion Magnetic Resonance Imaging ; Aged ; Biopsy, Large-Core Needle ; Nuclear magnetic resonance spectroscopy ; Magnetic resonance imaging ; Prostate cancer ; Trade and professional associations ; Index Medicus
    ISSN: 1464-4096
    E-ISSN: 1464-410X
    Source: Academic Search Ultimate
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 7
    Language: English
    In: Thorax, 2017-09, Vol.72 (9), p.861-863
    Description: HHT (Osler-Weber-Rendu disease) is an autosomal-dominant disease determined by multiple dilated vessels including mucocutaneous telangiectasias and vascular malformations of visceral organs resulting in recurrent epistaxis, gastrointestinal bleedings, paradoxical emboli, cerebral infarctions and abscesses. 1 In about 55% of patients with HHT type 1 (HHT-1) and about 10% of patients with HHT type 2 (HHT-2), large pulmonary arteriovenous malformations (PAVMs) are found which results in a direct shunting of arterial and venous blood flow. 2 These PAVMs cause a decreased resistance and enhanced likelihood of pulmonary haemorrhage. The ultrastructural analysis of these AV malformations by transmission electron microscopy highlighted dilated, thin-walled capillaries causing multiple diffuse alveolar haemorrhages which compress the surrounding lung tissue ( figure 3 A, B). Intussusceptive (non-sprouting) angiogenesis is a well-characterised rapid morphogenetic process observed during the capillary expansion in cancer, inflammation and regeneration, which is distinct from sprouting angiogenesis because it has no necessary requirement for cell proliferation. 4 In this respect, mechanical stress, the excessive recruitment of pericytes and smooth muscle cells related to the formation of PAVMs and the changes in blood flow are thought to play pivotal roles in the initiation of the intussusceptive microvascular growth.
    Subject(s): Young Adult ; Microscopy, Electron, Transmission ; Lung - pathology ; Telangiectasia, Hereditary Hemorrhagic - pathology ; Humans ; Microvessels - diagnostic imaging ; Microvessels - pathology ; Male ; Tomography, X-Ray Computed ; Lung - diagnostic imaging ; Telangiectasia, Hereditary Hemorrhagic - diagnostic imaging ; Lung - blood supply ; Angiogenesis ; Transmission electron microscopy ; Mutation ; Patients ; Index Medicus
    ISSN: 0040-6376
    E-ISSN: 1468-3296
    Source: HighWire Press (Free Journals)
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 8
    Language: English
    In: The FEBS journal, 2019-02, Vol.286 (4), p.803-820
    Description: Cytoplasmic dynein‐1 is a large minus‐end‐directed microtubule motor complex involved in membrane trafficking, organelle positioning, and microtubule organization. The roles of dynein light intermediate chains (DLICs; DLIC1 and DLIC2) within the complex are, however, still largely undefined. In this study, we investigated the possible roles of DLICs in epithelial homeostasis and colon cancer development. Mutant clonal analysis of Drosophila Dlic in the follicular epithelium of Drosophila ovary showed defects in nuclear positioning, epithelial integrity, and apical cell polarity. Consistently, knockdown of human DLIC1 and DLIC2 in colon carcinoma cells resulted in damaged epithelial organization, disturbed lumen formation, and impaired apical polarity establishment in three‐dimensional cell culture. Depletion of DLIC1 and DLIC2 led to reduced proliferation, enhanced apoptosis rates, disrupted mitotic spindle assembly, and induction of G2/M arrest in cell cycle progression. Moreover, reduced levels of DLIC1 in contrast to DLIC2 impaired the migratory ability. On the other hand, immunohistochemical examination of human colorectal tissue samples and further colorectal cancer dataset analysis showed a significant upregulation for DLIC1 in tumors, whereas DLIC2 expression was unchanged. In addition, the overexpression of DLIC1 caused increased proliferation, decreased apoptosis and enhanced migration, whereas DLIC2 overexpression did not result in any significant changes. Together, these results indicate that DLIC1 and DLIC2 contribute to the establishment and maintenance of epithelial homeostasis. Furthermore, these findings present the first evidence that DLIC1 and DLIC2 have distinct roles in colon cancer development and that DLIC1 may contribute to proliferative overgrowth and migratory characteristics. Cytoplasmic dynein 1 complexes contain either the dynein light intermediate chain (DLIC) 1 or 2 subunit, but not both of them, suggesting diverse dynein functions in respect to subunit heterogeneity. We investigated the possible roles of DLICs in epithelial homeostasis and colon cancer development. Increased levels of DLIC1, but not DLIC2, enhance proliferation, decrease apoptosis, and induce migration. Moreover, colon tumors show upregulation for DLIC1, but not for DLIC2. Diverse molecular interaction partners of DLIC1 and DLIC2 may define their discrete regulatory roles and different contributions to colon cancer development.
    Subject(s): cytoplasmic dynein 1 ; epithelial homeostasis ; dynein light intermediate chain ; colon cancer ; Index Medicus
    ISSN: 1742-464X
    E-ISSN: 1742-4658
    Source: Hellenic Academic Libraries Link
    Source: Academic Search Ultimate
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  • 9
    Language: English
    In: International journal of cancer, 2020-08-15, Vol.147 (4), p.1018-1026
    Description: Postmenopausal hormone replacement therapy (HRT) was found to be associated with lower risk of colorectal cancer (CRC). However, little is known regarding associations with molecular subtypes of CRC. The current study includes female participants of a large German population‐based case–control study (922 CRC cases and 1,183 controls). Tumor tissue samples were analyzed for microsatellite instability (MSI), CpG island methylator phenotype (CIMP), BRAF and KRAS mutation status. Multivariable logistic regression models were used to assess the association of HRT use with molecular subtypes and pathways. Postmenopausal HRT use was overall associated with reduced risk of CRC (adjusted odds ratio (aOR) 0.62, 95% confidence interval (CI) 0.50–0.76) and no major differences were observed for molecular subtypes or for tumor marker combinations representing molecular pathways. When stratified by median age (≤/〉71 years) potentially stronger risk reductions were observed in the older group for subtypes showing MSI (OR = 0.36, 95% CI 0.17–0.76), BRAF mutation (OR = 0.40, 95% CI 0.30–0.83) and CIMP‐high (OR = 0.40, 95% CI 0.21–0.73) and for CRC suggestive of the sessile serrated pathway (OR = 0.45, 95% CI 0.20–1.01). In conclusion, postmenopausal use of HRT was similarly associated with risk reduction of major molecular tumor subtypes and pathways of CRC. Potentially stronger risk reductions with CRC subtypes diagnosed at higher ages require confirmation and clarification from other studies. The current study extends the limited understanding of the mechanisms of HRT in CRC prevention. What's new? Evidence suggests that among women, risk of colorectal cancer (CRC) may be reduced by hormone replacement therapy (HRT). Little is known, however, about the impact of HRT on the risk of specific CRC molecular subtypes. In this analysis of female study participants in Germany, postmenopausal use of HRT was associated with a reduction in risk of major molecular subtypes of CRC, namely those characterized by microsatellite instability, CpG island methylator phenotype, or BRAF or KRAS mutations. Risk reductions were strongest for CRC subtypes diagnosed at older ages. The findings expand upon current knowledge of HRT mechanisms in CRC prevention.
    Subject(s): molecular epidemiology ; hormone replacement therapy ; sessile serrated ; colorectal neoplasms ; Colorectal Neoplasms - epidemiology ; Multivariate Analysis ; Risk Assessment - methods ; Microsatellite Instability ; Proto-Oncogene Proteins p21(ras) - genetics ; Colorectal Neoplasms - genetics ; Humans ; Middle Aged ; Risk Factors ; Logistic Models ; Case-Control Studies ; Germany - epidemiology ; Risk Assessment - statistics & numerical data ; Estrogen Replacement Therapy - methods ; Colorectal Neoplasms - therapy ; DNA Methylation ; Proto-Oncogene Proteins B-raf - genetics ; CpG Islands - genetics ; Postmenopause ; Female ; Aged ; Mutation ; Index Medicus
    ISSN: 0020-7136
    E-ISSN: 1097-0215
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 10
    Language: English
    In: The American journal of clinical nutrition, 2020-03-01, Vol.111 (3), p.562-569
    Description: ABSTRACT Background Observational studies have consistently shown that a high BMI is associated with increased risk of colorectal cancer (CRC). However, the underlying mechanisms linking obesity to CRC remain unclear. Objectives To investigate the associations of BMI and CRC by major molecular pathological subtypes of CRC. Methods This analysis included 2407 cases and 2454 controls from a large German population–based case–control study. Information on recent weight and height as well as other demographic and lifestyle data were obtained by standardized interviews. Multinomial logistic regression was used to estimate ORs and 95% CIs for the associations between BMI and risk of CRC by major molecular pathological features: microsatellite instability (MSI), CpG island methylator phenotype (CIMP), B-Raf proto-oncogene serine/threonine kinase (BRAF) mutation, and Kirsten rat sarcoma viral oncogene homolog gene (KRAS) mutation. Results Among women, a higher BMI was differentially and more strongly associated with risk of MSI CRC (OR per 5 kg/m2: 1.69; 95% CI: 1.34, 2.12; Pheterogeneity ≤ 0.001), CIMP-high CRC (OR per 5 kg/m2: 1.57; 95% CI: 1.30, 1.89; Pheterogeneity ≤ 0.001), BRAF-mutated CRC (OR per 5 kg/m2: 1.56; 95% CI: 1.22, 1.99; Pheterogeneity = 0.04), and KRAS-wildtype CRC (OR per 5 kg/m2: 1.35; 95% CI: 1.17, 1.54; Pheterogeneity = 0.01), compared with the risk of CRC in subjects with the molecular feature counterpart. In men, no meaningful differences in CRC risk were observed for the investigated molecular feature pairs. For the association of BMI with MSI CRC, we observed effect modification by sex (Pinteraction = 0.04). Also, in women, the risk of CRC with the serrated pathway features was more strongly increased with higher BMI than risk of CRC with the traditional pathway features (OR per 5 kg/m2: 1.73; 95% CI: 1.28, 2.34; Pheterogeneity = 0.01). Conclusions In women, the relation between BMI and MSI-high CRC seems to be stronger than that between BMI and microsatellite-stable CRC. However, a validation in an independent cohort is needed. This observational study was registered at the German Clinical Trials Register (http://www.drks.de; study ID: DRKS00011793), an approved primary register in the WHO network.
    Subject(s): Body Mass Index ; Microsatellite Instability ; Proto-Oncogene Proteins p21(ras) - genetics ; Colorectal Neoplasms - genetics ; Humans ; Middle Aged ; Male ; Case-Control Studies ; Colorectal Neoplasms - physiopathology ; Young Adult ; DNA Methylation ; Proto-Oncogene Proteins B-raf - genetics ; Aged, 80 and over ; CpG Islands ; Adult ; Female ; Aged ; Germany ; Index Medicus ; Abridged Index Medicus
    ISSN: 0002-9165
    E-ISSN: 1938-3207
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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