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Andrew Millar

Bio: Andrew Millar is an academic researcher from Middlesex University. The author has contributed to research in topics: Medicine & Cancer. The author has an hindex of 2, co-authored 4 publications receiving 649 citations.

Papers
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Journal ArticleDOI
TL;DR: This review examines the current understanding of the molecular genetics of colorectal carcinogenesis and concludes that gastroenterologists have a working knowledge of the pathological mechanisms that drive the disease.
Abstract: Colorectal cancer is a common but heterogeneous disease, which arises through the accumulation of genetic mutations Knowledge of the molecular basis of colorectal cancer has advanced at a rapid pace in recent years, reflecting progress made in the field of genomic medicine Targeted therapies have come into mainstream use, and the exciting prospect of treatment regimens tailored to the mutation profile of individual tumours is beginning to emerge In order to understand the development and application of the next generation of colorectal cancer treatments, it is important that gastroenterologists have a working knowledge of the pathological mechanisms that drive the disease This review examines our current understanding of the molecular genetics of colorectal carcinogenesis

708 citations

Journal ArticleDOI
TL;DR: In certain sectors of London, implementation of the pathway for management of women with hepatitis B and their infants is suboptimal and improved intersectorial sharing of information is needed to reduce the risk of women of high infectivity being lost to follow up.
Abstract: Pregnant women with hepatitis B virus (HBV) infection can transmit the infection to their infants, screening of patients and appropriate interventions reduce vertical transmission. This audit was conducted to assess adherence to the national guidelines for management of HBV infection in pregnancy. A retrospective audit was conducted on pregnant women diagnosed with hepatitis B on screening in antenatal clinics, across four hospitals in London over 2 years (2009–2010). Data was collected from antenatal records and discharge summaries using a standard audit form. The outcomes measured included HBV serological markers, HBV DNA, detection of other blood borne viruses and referral to hepatology services, administration of active and passive prophylaxis to infants at birth. Descriptive statistics are presented. Proportions were compared using the χ 2 test and 95% confidence intervals (CI) were calculated for prevalence estimates. Analyses were conducted using STATA 12. HBsAg was detected in 1.05% (n = 401, 95% CI 0.95-1.16) of women attending an antenatal appointment, 12% (n = 48) of the women were at a high risk of vertical transmission (HBe Ag positive or antiHBe and HBeAg negative or HBV DNA >106 IU/ml). Only 62% (n = 248) women were referred to hepatology or specialist clinics and 29% (n = 13) of women of high infectivity were on antiviral agents. Testing for hepatitis C and delta virus was suboptimal. 75% (n = 36) of the infants at a high risk of acquisition of HBV received both active and passive prophylaxis. In certain sectors of London, implementation of the pathway for management of women with hepatitis B and their infants is suboptimal. National guidelines should be followed and improved intersectorial sharing of information is needed to reduce the risk of women of high infectivity being lost to follow up.

16 citations

Journal ArticleDOI
21 Jan 2021-Cancers
TL;DR: In this article, the authors provide a critical analysis of available literature on COVID-19 and its impact on cancer management in general and that of UGI cancers in particular, and reflect on the impact of the first wave on the provision on diagnosis and management of with upper gastrointestinal (UGI) cancers.
Abstract: Coronavirus disease 2019 (COVID-19), caused by the novel, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, has left dramatic footprints on human health and economy. Cancer, whilst not an infective disease, is prevalent in epidemic proportions and cannot be pretermitted due to the impact of COVID-19. As we emanate from the second national lockdown in the UK with mixed feelings of hope and despair—due to vaccination and new COVID-19 variant, respectively—we reflect on the impact of the first wave on the provision on diagnosis and management of with upper gastrointestinal (UGI) cancers. This review provides a critical analysis of available literature on COVID-19 and its impact on cancer management in general and that of UGI cancers in particular.

4 citations

Journal ArticleDOI
TL;DR: In the UK, only 39% of cancer diagnoses were made via 2WW pathways in 2017, while significant proportions of diagnoses are made via other outpatient clinics (32%) or emergency presentation (19%), representing potentially missed diagnostic opportunities as mentioned in this paper.
Abstract: Early cancer diagnosis is a clinical and research priority of the UK government. Earlier cancer diagnosis should enable identification of cancers at an earlier stage, leading to improved outcomes.1 This must be balanced with the potential physical and psychological harms of over-investigation and over-diagnosis. The ‘two-week wait’ (2WW) referral pathway represents the most common route to cancer diagnosis. However, only 39% of cancer diagnoses were made via 2WW pathways in 2017, while significant proportions of diagnoses are made via other outpatient clinics (32%) or emergency presentation (19%), representing potentially missed diagnostic opportunities.2 Approximately 50% of cancer patients present with non-specific but concerning symptoms of cancer (NSCS).3 Compared to ‘alarm symptoms’ these have low predictive values for cancer and are less indicative of site-specific disease; consequently, they are not reflected in 2WW referral criteria.3 These patients frequently are referred later for specialist investigation and have more advanced disease.4 A principal goal for the new NHS Rapid Diagnostic Centres (RDCs) is to provide a pathway for patients with NSCS to detect cancer earlier, where treatment outcomes are more favourable.1 NHS England aims to provide full population coverage with RDCs by 2024.5 Despite their low predictive value and association with multiple diseases, many NSCS are considered as characteristic warning signs of cancer. These include unexpected weight loss, malaise, unexplained pain, new dyspnoea, and persistently abnormal blood tests.4,6,7 Unexpected weight loss was the most common symptom seen within an RDC pilot (66%) between 2016 and 2018;7 however, it has a relatively low predictive value for cancer.6,8,9 While patients with weight loss in isolation may not warrant further investigation, considering other clinical variables …

Cited by
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Journal ArticleDOI
Donna M. Muzny1, Matthew N. Bainbridge1, Kyle Chang1, Huyen Dinh1  +317 moreInstitutions (24)
19 Jul 2012-Nature
TL;DR: Integrative analyses suggest new markers for aggressive colorectal carcinoma and an important role for MYC-directed transcriptional activation and repression.
Abstract: To characterize somatic alterations in colorectal carcinoma, we conducted a genome-scale analysis of 276 samples, analysing exome sequence, DNA copy number, promoter methylation and messenger RNA and microRNA expression. A subset of these samples (97) underwent low-depth-of-coverage whole-genome sequencing. In total, 16% of colorectal carcinomas were found to be hypermutated: three-quarters of these had the expected high microsatellite instability, usually with hypermethylation and MLH1 silencing, and one-quarter had somatic mismatch-repair gene and polymerase e (POLE) mutations. Excluding the hypermutated cancers, colon and rectum cancers were found to have considerably similar patterns of genomic alteration. Twenty-four genes were significantly mutated, and in addition to the expected APC, TP53, SMAD4, PIK3CA and KRAS mutations, we found frequent mutations in ARID1A, SOX9 and FAM123B. Recurrent copy-number alterations include potentially drug-targetable amplifications of ERBB2 and newly discovered amplification of IGF2. Recurrent chromosomal translocations include the fusion of NAV2 and WNT pathway member TCF7L1. Integrative analyses suggest new markers for aggressive colorectal carcinoma and an important role for MYC-directed transcriptional activation and repression.

6,883 citations

Journal ArticleDOI
07 May 2015-Cell
TL;DR: Tumor organoids are amenable to high-throughput drug screens allowing detection of gene-drug associations and may fill the gap between cancer genetics and patient trials, complement cell-line- and xenograft-based drug studies, and allow personalized therapy design.

1,547 citations

Journal ArticleDOI
TL;DR: According to GLOBOCAN 2018 data, colorectal cancer (CRC) is the third most deadly and fourth most commonly diagnosed cancer in the world.
Abstract: According to GLOBOCAN 2018 data, colorectal cancer (CRC) is the third most deadly and fourth most commonly diagnosed cancer in the world. Nearly 2 million new cases and about 1 million deaths are expected in 2018. CRC incidence has been steadily rising worldwide, especially in developing countries that are adopting the "western" way of life. Obesity, sedentary lifestyle, red meat consumption, alcohol, and tobacco are considered the driving factors behind the growth of CRC. However, recent advances in early detection screenings and treatment options have reduced CRC mortality in developed nations, even in the face of growing incidence. Genetic testing and better family history documentation can enable those with a hereditary predisposition for the neoplasm to take preventive measures. Meanwhile, the general population can reduce their risk by lowering their red meat, alcohol, and tobacco consumption and raising their consumption of fibre, wholesome foods, and certain vitamins and minerals.

1,154 citations

Journal ArticleDOI
30 Aug 2012-Nature
TL;DR: The R-spondin gene fusions, several new recurrent mutations in the Wnt pathway gene TCF7L2, chromatin-remodelling genes such as TET2 and TET3 and receptor tyrosine kinases including ERBB3 are identified and shown to be capable of potentiating Wnt signalling.
Abstract: Identifying and understanding changes in cancer genomes is essential for the development of targeted therapeutics1. Here we analyse systematically more than 70 pairs of primary human colon tumours by applying next-generation sequencing to characterize their exomes, transcriptomes and copy-number alterations. We have identified 36,303 protein-altering somatic changes that include several new recurrent mutations in the Wnt pathway gene TCF7L2, chromatin-remodelling genes such as TET2 and TET3 and receptor tyrosine kinases including ERBB3. Our analysis for significantly mutated cancer genes identified 23 candidates, including the cell cycle checkpoint kinase ATM. Copy-number and RNA-seq data analysis identified amplifications and corresponding overexpression of IGF2 in a subset of colon tumours. Furthermore, using RNA-seq data we identified multiple fusion transcripts including recurrent gene fusions involving R-spondin family members RSPO2 and RSPO3 that together occur in 10% of colon tumours. The RSPO fusions were mutually exclusive with APC mutations, indicating that they probably have a role in the activation of Wnt signalling and tumorigenesis. Consistent with this we show that the RSPO fusion proteins were capable of potentiating Wnt signalling. The R-spondin gene fusions and several other gene mutations identified in this study provide new potential opportunities for therapeutic intervention in colon cancer.

914 citations

Journal ArticleDOI
TL;DR: The results suggest that 'driver' pathway mutations enable stem cell maintenance in the hostile tumor microenvironment, but that additional molecular lesions are required for invasive behavior.
Abstract: Genome editing applied to human intestinal organoids enables the study of the functional effects of mutations recurrent in human tumors.

847 citations