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  1. Article ; Online: Modifiable Risk Factors and Risk of Colorectal and Endometrial Cancers in Lynch Syndrome: A Systematic Review and Meta-Analysis.

    Power, Robert F / Doherty, Damien E / Parker, Imelda / Gallagher, David J / Lowery, Maeve A / Cadoo, Karen A

    JCO precision oncology

    2024  Volume 8, Page(s) e2300196

    Abstract: Purpose: Lynch syndrome is the most common hereditary cause of colorectal and endometrial cancers. Modifiable risk factors, including obesity, physical activity, alcohol intake, and smoking, are well-established in sporadic cancers but are less studied ... ...

    Abstract Purpose: Lynch syndrome is the most common hereditary cause of colorectal and endometrial cancers. Modifiable risk factors, including obesity, physical activity, alcohol intake, and smoking, are well-established in sporadic cancers but are less studied in Lynch syndrome.
    Methods: Searches were conducted on MEDLINE, Embase, and Web of Science for cohort studies that investigated the association between modifiable risk factors and the risk of colorectal or endometrial cancer in people with Lynch syndrome. Adjusted hazard ratios (HRs) and 95% CIs for colorectal and endometrial cancers were pooled using a random effects model. The protocol was prospectively registered on PROSPERO (CRD 42022378462), and the meta-analysis was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-Analysis of Observational Studies in Epidemiology reporting guidelines.
    Results: A total of 770 citations were reviewed. Eighteen studies were identified for qualitative synthesis, with seven colorectal cancer (CRC) studies eligible for meta-analysis. Obesity (HR, 2.38 [95% CI, 1.52 to 3.73]) was associated with increased CRC risk. There was no increased CRC risk associated with smoking (HR, 1.04 [95% CI, 0.82 to 1.32]) or alcohol intake (HR, 1.32 [95% CI, 0.97 to 1.81]). Type 2 diabetes mellitus (T2DM) and some dietary factors might increase risk of CRC although more studies are needed. In a qualitative synthesis of three endometrial cancer cohort studies, female hormonal risk factors and T2DM may affect the risk of endometrial cancer, but obesity was not associated with an increased risk.
    Conclusion: Lifestyle recommendations related to weight and physical activity may also be relevant to cancer prevention for individuals with Lynch syndrome. Further high-quality prospective cohort studies, in particular, including endometrial cancer as an end point, are needed to inform evidence-based cancer prevention strategies in this high-risk population.
    MeSH term(s) Female ; Humans ; Colorectal Neoplasms, Hereditary Nonpolyposis/epidemiology ; Colorectal Neoplasms, Hereditary Nonpolyposis/genetics ; Diabetes Mellitus, Type 2/epidemiology ; Endometrial Neoplasms/epidemiology ; Obesity/epidemiology ; Prospective Studies ; Risk Factors
    Language English
    Publishing date 2024-01-11
    Publishing country United States
    Document type Journal Article ; Meta-Analysis ; Systematic Review
    ISSN 2473-4284
    ISSN (online) 2473-4284
    DOI 10.1200/PO.23.00196
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Prostate cancer: germline prediction for a commonly variable malignancy.

    Bambury, Richard M / Gallagher, David J

    BJU international

    2012  Volume 110, Issue 11 Pt C, Page(s) E809–18

    Abstract: Unlabelled: What's known on the subject? and What does the study add? Prostate cancer is a heterogeneous disease and biomarkers to predict its incidence and subsequent clinical behaviour are needed to tailor screening, prevention and therapeutic ... ...

    Abstract Unlabelled: What's known on the subject? and What does the study add? Prostate cancer is a heterogeneous disease and biomarkers to predict its incidence and subsequent clinical behaviour are needed to tailor screening, prevention and therapeutic strategies. Rare mutations in genes such as BRCA1, BRCA2 and HOXB13 can affect prostate cancer incidence and/or clinical behaviour. Genome wide association studies (GWAS) have identified more common genetic variations that explain an estimated 20% of familial prostate cancer risk. In this review, we focus on the potential of germline genetic variation to provide biomarkers for prostate cancer screening, prevention and management. We discuss how germline genetics may have a role in treatment selection if reliable pharmacogenetic predictors of efficacy and toxicity can be identified. We have outlined possible mechanisms for including germline investigation in future prostate cancer clinical trials.
    Objectives: • Prostate cancer is a heterogeneous disease and biomarkers to predict its incidence and subsequent clinical behaviour are needed to tailor screening, prevention and therapeutic strategies. • In this review we focus on the potential of germline genetic variation to provide these biomarkers.
    Methods: • We review the published literature on germline genetics in prostate cancer and examine the possibility of including germline genetic biomarkers in future prostate cancer clinical trials.
    Results: • Rare mutations in genes such as BRCA1, BRCA2 and HOXB13 can affect prostate cancer incidence and/or clinical behaviour. • Genome-wide association studies (GWAS) have identified more common genetic variations that explain an estimated 20% of familial prostate cancer risk. • Germline genetics may have a role in treatment selection, if reliable pharmacogenetic predictors of efficacy and toxicity can be identified.
    Conclusion: • This rapidly emerging area of prostate cancer research may provide answers to current clinical conundrums in the prostate cancer treatment paradigm. We have outlined possible mechanisms for including germline investigation in future prostate cancer clinical trial design.
    MeSH term(s) Genetic Predisposition to Disease ; Genome-Wide Association Study/methods ; Germ-Line Mutation ; Global Health ; Humans ; Incidence ; Male ; Prostatic Neoplasms/epidemiology ; Prostatic Neoplasms/genetics ; Prostatic Neoplasms/pathology
    Language English
    Publishing date 2012-12
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1462191-5
    ISSN 1464-410X ; 1464-4096 ; 1358-8672
    ISSN (online) 1464-410X
    ISSN 1464-4096 ; 1358-8672
    DOI 10.1111/j.1464-410X.2012.11450.x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Extramural venous invasion (EMVI) in colorectal cancer is associated with increased cancer recurrence and cancer-related death.

    Mc Entee, Philip D / Shokuhi, Poorya / Rogers, Ailin C / Mehigan, Brian J / McCormick, Paul H / Gillham, Charles M / Kennedy, M John / Gallagher, David J / Ryan, Ciara E / Muldoon, Cian B / Larkin, John O

    European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology

    2022  Volume 48, Issue 7, Page(s) 1638–1642

    Abstract: Introduction: Colorectal cancer (CRC) outcomes vary depending on tumour biology, with several features used to predict disease behaviour. Extramural venous invasion (EMVI) is associated with negative outcomes and its presence has been established as an ... ...

    Abstract Introduction: Colorectal cancer (CRC) outcomes vary depending on tumour biology, with several features used to predict disease behaviour. Extramural venous invasion (EMVI) is associated with negative outcomes and its presence has been established as an indicator of more aggressive disease in CRC.
    Methods: A prospectively maintained database was examined for patients undergoing curative resection for non-metastatic CRC between 2012 and 2018 in a tertiary institution. Clinicopathological factors were compared to assess their impact on recurrence, all-cause mortality and cancer-related death. Kaplan Meier analysis of the association between EMVI and these endpoints was performed, and univariable and multivariable analysis was carried out to establish the relationship of predictive factors in oncological outcomes.
    Results: Eighty-eight (13.5%) of 654 patients developed recurrence. The mean time to recurrence was 19.8 ± 13.5 months. There were 36 (5.5%) cancer-related deaths at a mean duration of follow-up of 46.3 ± 21.6 months. Two hundred and sixty-six patients had extramural venous invasion (40.7%). EMVI was significantly associated with reduced overall recurrence-free survival, systemic recurrence-free survival, and increased cancer-related death on univariate analysis (p < 0.001 for all, Fig. 1), and multivariable analysis (OR 1.8 and 2.1 respectively, p < 0.05 for both).
    Conclusion: EMVI is associated with a poor prognosis, independent of stage, nodal status and other histopathological features. The presence of EMVI should be strongly considered as an indication for adjuvant therapy.
    MeSH term(s) Colorectal Neoplasms/pathology ; Colorectal Neoplasms/surgery ; Combined Modality Therapy ; Humans ; Kaplan-Meier Estimate ; Neoplasm Invasiveness/pathology ; Neoplasm Recurrence, Local/epidemiology ; Neoplasm Recurrence, Local/pathology ; Prognosis ; Rectal Neoplasms/pathology ; Retrospective Studies
    Language English
    Publishing date 2022-02-19
    Publishing country England
    Document type Journal Article
    ZDB-ID 632519-1
    ISSN 1532-2157 ; 0748-7983
    ISSN (online) 1532-2157
    ISSN 0748-7983
    DOI 10.1016/j.ejso.2022.02.013
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Uptake of BRCA1/BRCA2 predictive genetic testing in an Irish population is low: a missed opportunity.

    O'Reilly, David E / Dooley, Lucy / Watson, Geoffrey A / Clarke, Roisin / Nolan, Amy / Nolan, Carmel / Berkeley, Eileen / Farrell, Michael / McDevitt, Trudi / Rogers, Melissa / Clabby, Catherine / Gallagher, David J

    Irish journal of medical science

    2022  Volume 192, Issue 4, Page(s) 1607–1611

    Abstract: Introduction: Predictive testing for BRCA1 or BRCA2 allows at-risk individuals to engage with appropriate screening and treatment services if a pathogenic mutation is identified. Previous studies have shown uptake of predictive testing to most commonly ... ...

    Abstract Introduction: Predictive testing for BRCA1 or BRCA2 allows at-risk individuals to engage with appropriate screening and treatment services if a pathogenic mutation is identified. Previous studies have shown uptake of predictive testing to most commonly range between 20% and 40% (Table 2). This represents a missed cancer prevention opportunity. Possible explanations for this low uptake include lack of disclosure of at-risk status to relatives, lack of awareness of cancer genetics services, or patient preference. The goal of the current study was to investigate the uptake of BRCA1 or BRCA2 predictive testing in an Irish population.
    Methods: We performed a multicentre, retrospective analysis of 63 pedigrees from two Irish tertiary referral hospitals over a five-year period (2012-2017). Family pedigrees were reviewed to identify at-risk family members eligible for predictive BRCA1 or BRCA2 mutation testing as per international guidelines, and testing rates were determined.
    Results: A total of 1048 eligible individuals were identified, 318 (30.4%) proceeded to BRCA1 or BRCA2 germline testing including [215 (37.5%) females and 99 males (21.5%)]. Women were significantly more likely to test than men (T = 3.7, p < .0002). Uptake of testing was significant higher amongst first-degree relatives 45% (150/323) compared to 20% (50/258) amongst second degree relatives, and 10 % (33/317) amongst more distant relatives (F = 25.32, p < 0.00001).
    Conclusions: Uptake of BRCA1 OR BRCA2 mutation testing in Ireland is suboptimal, particularly amongst Irish males and distant relatives. Further research is needed to identify strategies which may improve uptake within current legal and ethical frameworks.
    MeSH term(s) Female ; Humans ; Male ; BRCA1 Protein/genetics ; BRCA2 Protein/genetics ; Genetic Predisposition to Disease ; Genetic Testing ; Mutation ; Neoplasms/genetics ; Retrospective Studies
    Chemical Substances BRCA1 Protein ; BRCA1 protein, human ; BRCA2 Protein ; BRCA2 protein, human
    Language English
    Publishing date 2022-10-19
    Publishing country Ireland
    Document type Journal Article
    ZDB-ID 390895-1
    ISSN 1863-4362 ; 0021-1265
    ISSN (online) 1863-4362
    ISSN 0021-1265
    DOI 10.1007/s11845-022-03176-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Improving response and outcomes for patients with liver-limited metastatic colorectal cancer.

    Gallagher, David J / Kemeny, Nancy

    Clinical colorectal cancer

    2010  Volume 9 Suppl 1, Page(s) S36–43

    Abstract: Long-term survival with colorectal liver metastases (CLM) usually requires surgical resection, despite considerable improvements in systemic chemotherapy that have extended median survival with metastatic colorectal cancer from 6 months to in excess of 2 ...

    Abstract Long-term survival with colorectal liver metastases (CLM) usually requires surgical resection, despite considerable improvements in systemic chemotherapy that have extended median survival with metastatic colorectal cancer from 6 months to in excess of 2 years. Multidisciplinary management is now the norm in the perioperative setting, and chemotherapy has become part of an accepted treatment paradigm. Systemic and intrahepatic chemotherapy can shrink inoperable disease to the point of resection, and a combination of neoadjuvant and adjuvant chemotherapy improves disease-free survival for patients with operable CLM. A greater understanding of the biology of colorectal metastasis has revealed many new potential targets, and carefully designed clinical trials are required to investigate these and other existing biologic therapies in this setting. In this article we discuss the biology of colorectal cancer metastases, the rationale for perioperative chemotherapy, and the recent and ongoing investigation of perioperative chemotherapy in the management of CLM.
    MeSH term(s) Animals ; Antineoplastic Agents/therapeutic use ; Colorectal Neoplasms/pathology ; Colorectal Neoplasms/therapy ; Combined Modality Therapy ; Hepatectomy ; Humans ; Liver Neoplasms/secondary ; Liver Neoplasms/therapy ; Quality Improvement ; Radiotherapy ; Treatment Outcome
    Chemical Substances Antineoplastic Agents
    Language English
    Publishing date 2010-06
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2112638-0
    ISSN 1938-0674 ; 1533-0028
    ISSN (online) 1938-0674
    ISSN 1533-0028
    DOI 10.3816/CCC.2010.s.005
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Metastatic colorectal cancer: from improved survival to potential cure.

    Gallagher, David J / Kemeny, Nancy

    Oncology

    2010  Volume 78, Issue 3-4, Page(s) 237–248

    Abstract: Context: The treatment of colorectal cancer has improved considerably in recent years, but it remains the second commonest cause of cancer deaths in men and women in the United States. Better therapies have resulted in prolonged median survival for ... ...

    Abstract Context: The treatment of colorectal cancer has improved considerably in recent years, but it remains the second commonest cause of cancer deaths in men and women in the United States. Better therapies have resulted in prolonged median survival for patients with metastatic disease and a select number of patients can now be cured.
    Evidence acquisition: We conducted a computerized search using PubMed and Google Scholar for reports published between January 1993 and August 2009 using mesh headings and key words relating to the treatment of colorectal cancer. If reports identified by these criteria referred to other papers not in the initial search, then these were also reviewed if relevant to metastatic colorectal cancer (MCRC).
    Results: Seven new chemotherapy agents have been licensed for the treatment of advanced colorectal cancer, with associated improved median survival from 5 months to 2 years. Complete responses are rare with systemic chemotherapy alone, but higher overall response rates to systemic and intrahepatic chemotherapies have enabled initially unresectable patients to undergo potentially curative surgical resection of metastases. Improved surgical expertise together with the adjunctive use of radiofrequency ablation has further expanded the definition of resectability. Advances in the understanding of tumor biology have resulted in the development of clinically useful biomarkers and the emergence of active biological therapies.
    Conclusions: The multidisciplinary management of MCRC incorporating improved systemic and local therapies continues to improve median survival and enlarge the cohort of patients that can be approached with curative intent. Recent technological advances have facilitated a better understanding of tumor biology that promises continued advancements in patient care.
    MeSH term(s) Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biomarkers, Tumor ; Camptothecin/administration & dosage ; Camptothecin/analogs & derivatives ; Catheter Ablation ; Colonic Neoplasms/metabolism ; Colonic Neoplasms/pathology ; Female ; Fluorouracil/therapeutic use ; Humans ; Liver Neoplasms/secondary ; Liver Neoplasms/surgery ; Male ; Medical Oncology/methods ; Neoplasm Metastasis ; Organoplatinum Compounds/administration & dosage ; Time Factors ; Treatment Outcome
    Chemical Substances Biomarkers, Tumor ; Organoplatinum Compounds ; oxaliplatin (04ZR38536J) ; irinotecan (7673326042) ; Fluorouracil (U3P01618RT) ; Camptothecin (XT3Z54Z28A)
    Language English
    Publishing date 2010
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 250101-6
    ISSN 1423-0232 ; 0030-2414
    ISSN (online) 1423-0232
    ISSN 0030-2414
    DOI 10.1159/000315730
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Aqueous Photoelectrochemical CO2 Reduction to CO and Methanol over a Silicon Photocathode Functionalized with a Cobalt Phthalocyanine Molecular Catalyst.

    Shang, Bo / Rooney, Conor L / Gallagher, David J / Wang, Bernie / Krayev, Andrey / Shema, Hadar / Leitner, Oliver / Harmon, Nia J / Xiao, Langqiu / Sheehan, Colton / Bottum, Samuel R / Gross, Elad / Cahoon, James F / Mallouk, Thomas E / Wang, Hailiang

    Angewandte Chemie (International ed. in English)

    2022  

    Abstract: We report a precious-metal-free molecular catalyst-based photocathode that is active for aqueous CO2 reduction to CO and methanol. The photoelectrode is composed of cobalt phthalocyanine molecules anchored on graphene oxide and integrated via a (3- ... ...

    Abstract We report a precious-metal-free molecular catalyst-based photocathode that is active for aqueous CO2 reduction to CO and methanol. The photoelectrode is composed of cobalt phthalocyanine molecules anchored on graphene oxide and integrated via a (3-aminopropyl)triethoxysilane linker to p-type silicon protected by a thin film of titanium dioxide. The photocathode reduces CO2 to CO with high selectivity at potentials as mild as 0 V versus the reversible hydrogen electrode (vs RHE). Methanol production is observed at an onset potential of -0.36 V vs RHE, and reaches a peak turnover frequency of 0.18 s-1. To date, this is the only molecular catalyst-based photoelectrode that is active for the six-electron reduction of CO2 to methanol. This work puts forth a strategy for interfacing molecular catalysts to p-type semiconductors and demonstrates state-of-the-art performance for photoelectrochemical CO2 reduction to CO and methanol.
    Language English
    Publishing date 2022-11-29
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2011836-3
    ISSN 1521-3773 ; 1433-7851
    ISSN (online) 1521-3773
    ISSN 1433-7851
    DOI 10.1002/anie.202215213
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Colorectal hepatic metastases: adjuvant chemotherapy and survival.

    Gallagher, David J / Kemeny, Nancy E

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology

    2009  Volume 27, Issue 20, Page(s) e18–9; author reply e20–1

    MeSH term(s) Adenocarcinoma/drug therapy ; Adenocarcinoma/secondary ; Adenocarcinoma/surgery ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Chemotherapy, Adjuvant ; Colorectal Neoplasms/pathology ; Hepatectomy ; Humans ; Liver Neoplasms/secondary ; Liver Neoplasms/surgery ; Survival Analysis
    Language English
    Publishing date 2009-07-10
    Publishing country United States
    Document type Comment ; Letter
    ZDB-ID 604914-x
    ISSN 1527-7755 ; 0732-183X
    ISSN (online) 1527-7755
    ISSN 0732-183X
    DOI 10.1200/JCO.2009.22.4626
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Bladder cancer.

    Gallagher, David J / Milowsky, Matthew I

    Current treatment options in oncology

    2009  Volume 10, Issue 3-4, Page(s) 205–215

    Abstract: Bladder cancer is a complex disease of older patients with coexisting medical problems requiring multimodal therapy. For patients with localized bladder cancer, standard management for superficial disease includes transurethral resection with or without ... ...

    Abstract Bladder cancer is a complex disease of older patients with coexisting medical problems requiring multimodal therapy. For patients with localized bladder cancer, standard management for superficial disease includes transurethral resection with or without intravesical therapy, while muscle-invasive cancer is managed with neoadjuvant cisplatin- based chemotherapy followed by radical cystectomy. Comorbid conditions prevent many older patients from receiving cisplatin-based chemotherapy and/or undergoing surgery. Tri-modality bladder preservation approaches including a complete transurethral resection of the bladder tumor (TURBT) followed by combined chemotherapy and radiation have generally included only those patients who are candidates for a salvage cystectomy. Future research must specifically focus on older adults with bladder cancer including non-cisplatin-based neoadjuvant regimens; bladder preservation strategies using alternative non-cisplatin chemotherapy in noncystectomy candidates; clinical trials evaluating novel targeted agents in older adults; and geriatric assessment tools to assist in decision making.
    MeSH term(s) Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Clinical Trials as Topic ; Comorbidity ; Female ; Geriatrics/methods ; Humans ; Male ; Medical Oncology/methods ; Neoplasm Invasiveness ; Treatment Outcome ; Urinary Bladder Neoplasms/diagnosis ; Urinary Bladder Neoplasms/therapy
    Chemical Substances Antineoplastic Agents
    Language English
    Publishing date 2009-09-23
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2057351-0
    ISSN 1534-6277 ; 1527-2729
    ISSN (online) 1534-6277
    ISSN 1527-2729
    DOI 10.1007/s11864-009-0112-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Insertion of an SVA element in MSH2 as a novel cause of Lynch syndrome.

    Yang, Ciyu / Li, Yirong / Trottier, Magan / Farrell, Michael P / Rai, Vikas K / E Salo-Mullen, Erin / Gallagher, David J / Stadler, Zsofia K / van der Klift, Heleen M / Zhang, Liying

    Genes, chromosomes & cancer

    2021  Volume 60, Issue 8, Page(s) 571–576

    Abstract: Germline mutations in the DNA mismatch repair (MMR) genes cause Lynch syndrome (LS). In this study, we identified and characterized a novel SINE-VNTR-Alu (SVA) insertion in exon 12 of MSH2 in an individual with early-onset colorectal cancer and a very ... ...

    Abstract Germline mutations in the DNA mismatch repair (MMR) genes cause Lynch syndrome (LS). In this study, we identified and characterized a novel SINE-VNTR-Alu (SVA) insertion in exon 12 of MSH2 in an individual with early-onset colorectal cancer and a very strong LS family history. RT-PCR analysis indicated a larger aberrant MSH2 transcript in one of the family members. MSK-IMPACT next-generation sequencing and long-range PCR analyses revealed an insertion in MSH2 exon 12 at the c.1972 position in an antisense orientation. The insertion was further characterized as an SVA element approximately 3 kb in length, belonging to the SVA_F1 family of retrotransposons. This variant also segregated with LS related cancers in four affected family members in this family. Based on this evidence, this MSH2 SVA insertion is considered pathogenic.
    MeSH term(s) Alu Elements ; Colorectal Neoplasms, Hereditary Nonpolyposis/genetics ; Colorectal Neoplasms, Hereditary Nonpolyposis/pathology ; Humans ; Male ; Middle Aged ; Minisatellite Repeats ; MutS Homolog 2 Protein/genetics
    Chemical Substances MSH2 protein, human (EC 3.6.1.3) ; MutS Homolog 2 Protein (EC 3.6.1.3)
    Language English
    Publishing date 2021-04-21
    Publishing country United States
    Document type Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1018988-9
    ISSN 1098-2264 ; 1045-2257
    ISSN (online) 1098-2264
    ISSN 1045-2257
    DOI 10.1002/gcc.22950
    Database MEDical Literature Analysis and Retrieval System OnLINE

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