The WordPress.com stats helper monkeys prepared a 2012 annual report for this blog.
Here’s an excerpt:
600 people reached the top of Mt. Everest in 2012. This blog got about 5,000 views in 2012. If every person who reached the top of Mt. Everest viewed this blog, it would have taken 8 years to get that many views.
Cancer Research UK-funded scientists have discovered that two gene faults increase the risk of bowel cancer in families with a strong history of developing the disease, who, until now, had no explanation as to why their risk was greater. The research is published in Nature Genetics1.
To find the faults, the researchers from the University of Oxford and The Institute of Cancer Research, London, scanned the genes of 20 people2 from families with a strong history of bowel cancer. They found everyone who had a faulty POLE or POLD1 gene developed bowel cancer or had a precancerous growth in the bowel.
The two genes are so-called ‘dominant’ genes, where only one faulty copy needs to be inherited for someone to be at a high risk of developing bowel cancer.
To confirm their findings they then looked for the faults in almost 4,000 people with bowel cancer and 6,700 without the disease. Neither of the faults were found in people without bowel cancer, while 12 people with the POLE gene were found in the bowel cancer group and one person had a POLD1 gene fault.
The POLD1 fault was also found to increase the risk of getting womb cancer and possibly brain tumours with seven people in the study being diagnosed with womb cancer and one developing two brain tumours.
Cancer Research UK’s Professor Ian Tomlinson, lead researcher based at the University of Oxford, said: “There are some families where large numbers of relatives develop bowel cancer but who don’t have any of the known gene faults that raise the risk of developing the disease.
“These two faults are rare, but if you inherit them your chance of bowel cancer is high. By testing people with a strong family history of the disease for these faults, we can identify those who are at high risk and try to prevent the disease by using colonoscopy and other methods.”
POLE and POLD1 are involved in scanning and repairing damage to DNA, removing incorrect sequences from the DNA chain. Without these genes, affected individuals build up damage in their DNA which can cause bowel cancer.
Study co-leader Professor Richard Houlston from The Institute of Cancer Research said: “Uncovering gene faults like these two is extremely important, as inherited susceptibility plays a role in the development of about a third of all cases of colorectal cancer.
“This is one of the most important discoveries in bowel cancer genetics in years. It should allow us to manage families affected by inherited bowel cancer much more effectively, and it offers new clues for the prevention or treatment of all forms of the disease.”
Joe Wiegand, a financial advisor from Hampshire, was diagnosed with bowel cancer seven and a half years ago at just 28 years old. Joe had most of his large bowel removed and six months of chemotherapy. His treatment was successful and he is now followed up once a year with a sigmoidoscopy. As many of Joe’s relatives had also had bowel cancer, during his treatment he was invited to take part in this study to investigate genetic faults that may be behind his cancer.
Joe said: “There’s a very strong history of bowel cancer in my family – my dad’s mother and sister both had it, my dad was diagnosed with it at 43 and a few cousins have had bowel cancers and brain tumours. It’s clear that something’s going on in our family. I hope that taking part in this study will spare my two children the uncertainty of not knowing if they have this gene fault by having a simple yes or no blood test.”
Dr Julie Sharp, senior science information manager at Cancer Research UK, said: “This research provides another piece of the puzzle for families who have a much greater risk of developing bowel cancer.
“Cancer Research UK scientists have played an important role in finding the gene faults that increase cancer risk. Their work means doctors can help families with a strong family history by preventing cancer from developing or diagnosing it earlier to help more people survive.”
Palles, C et al Germline mutations in the proof-reading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas Nature Genetics (2012)
Age, sex, and income as well as the type of cancer influence the stage at which patients’ cancer is diagnosed, a study has found.
Eliminating these demographic inequalities would help improve the chances of a cure for up to 5600 patients in England with seven common cancers each year, the researchers have estimated.
For the study, published in the Annals of Oncology, researchers from the University of Cambridge and the Eastern Cancer Registration and Information Centre examined data on the stage at diagnosis of nearly 100 000 patients with any of 10 different cancers, including the five most common (lung, breast, prostate, colon, and rectal cancers) and also bladder, kidney, ovarian, and endometrial cancers and melanoma.1
They found that melanoma and prostate, endometrial, and breast cancers in patients in the most deprived socioeconomic groups were more likely than those in the least deprived to be diagnosed in advanced stages. The increase in risk of late diagnosis according to deprivation ranged from more than double for melanoma (odds ratio 2.24 (1.66 to 3.03) to a third more for breast cancer (1.31 (1.15 to 1.49)).
For other cancers age and sex were important determinants of late diagnosis. Men with melanoma and those with lung cancer were more likely to have their cancer diagnosed at an advanced stage than were women with the same cancer.
The researchers also found that for melanoma and breast, prostate, and endometrial cancers older patients were more likely to be given a diagnosis at an advanced stage. But for lung, bladder, and renal cancers the opposite was true, with diagnosis at an advanced stage being less likely among older patients. This may be because older patients had more tests than younger patients, say the researchers.
During the study period, 2006-10, there were no notable social inequalities in the risk of diagnosis at an advanced stage among patients with bowel cancer and among women with ovarian cancer.
Because melanoma and breast and endometrial cancers are easy to diagnose, delays in detecting these cancers are probably because of patients’ lack of awareness of symptoms, say the researchers.
The lead author, Georgios Lyratzopoulos, a researcher at the University of Cambridge, said, “We know that earlier stage diagnosis of cancer is important: it dramatically improves the effectiveness of treatment and survival for many cancers. This study documents the importance of awareness of cancer symptoms and signs by patients of all social groups. It provides clear evidence about which patient groups would benefit most from targeted campaigns to raise awareness of different cancers.”
The findings could help target publicity about cancer at groups at high risk of late diagnosis, say the researchers. For example, older men from deprived groups would benefit from information about melanoma, while older women could be targeted with material on breast and endometrial cancers.
Cite this as: BMJ 2012;345:e7669
But highest familial risk still in relatives whose parents diagnosed at earlier ages
Research: Familial risk of early and late onset cancer: nationwide prospective cohort study
Relatives of family members diagnosed with cancer are still at risk of the disease even if the diagnosis came at an older age, suggests a paper published on bmj.com today.
It is known that early onset cancer cases carry more hereditary risk than late onset cases, but little is known about whether any familial component exists in cancer at a very old age.
Researchers from the German Cancer Research Centre and Lund University in Sweden therefore took data from the Swedish Family-Cancer Database (the largest one of its kind) on just under eight million offspring and their biological parents.
Parents’ ages were not limited but offspring were all 0-76 years old. Follow-up was started at birth, immigration date or 1961, whichever came latest. Follow-up ended on year of diagnosis of first cancer, death, emigration or 2008.
Results were adjusted for several factors including age, sex, socioeconomic status, residential area, hospitalisation for obesity, COPD and alcohol consumption.
The highest risk was seen in cases whose parents were diagnosed at earlier ages. However, even when parents were affected in old age (80+) and for some cancers in very old age (90+), the risk of the same cancer in offspring was significantly higher than those whose parents were not affected.
Increased risks for each cancer were as follows (in offspring aged 0-76 years): non-Hodgkin lymphoma 1.6%; urinary bladder 2.8%; skin 3.5%; melanoma 4.6%; lung 5%; colorectal 6.4%; breast 8.8% and prostate 30.1%.
In the study population, 35-81% of all familial cancers in parents occurred over 69 years of age (colorectal: 59%, lung: 56%, breast 41%, prostate: 75%, urinary bladder: 62%, and skin cancer: 81%, melanoma: 35%, and non-Hodgkin’s lymphoma: 54%). Therefore, the majority of familial cancers occur at elderly ages.
Attempts to explain familial risks by non-genetic factors were not convincing. Therefore, the researchers concluded that familial risks have largely genetic bases.
The researchers believe that family members (in particular offspring) may benefit from knowing that they’re at increased risk of a particular cancer because it allows them to avoid known modifiable risk factors for that cancer.
Click here to see full study: http://bit.ly/Zqhrv0
Division of Molecular Genetic Epidemiology, German Cancer Research Centre, 69120 Heidelberg, Germany.
To determine whether familial risk of cancer is limited to early onset cases.
Nationwide prospective cohort study. SETTING : Nationwide Swedish Family-Cancer Database.
All Swedes born after 1931 and their biological parents, totalling >12.2 million individuals, including >1.1 million cases of first primary cancer.
The highest familial risk was seen for offspring whose parents were diagnosed at an early age. Familial risks were significantly increased for colorectal, lung, breast, prostate, and urinary bladder cancer and melanoma, skin squamous cell carcinoma, and non-Hodgkin’s lymphoma, even when parents were diagnosed at age 70-79 or 80-89. When parents were diagnosed at more advanced ages (≥90), the risk of concordant cancer in offspring was still significantly increased for skin squamous cell carcinoma (hazard ratio 1.9, 95% confidence interval 1.4 to 2.7), colorectal (1.6, 1.2 to 2.0), breast (1.3, 1.0 to 1.6), and prostate cancer (1.3, 1.1 to 1.6). For offspring with a cancer diagnosed at ages 60-76 whose parents were affected at age <50, familial risks were not significantly increased for nearly all cancers.
Though the highest familial risks of cancer are seen in offspring whose parents received a diagnosis of a concordant cancer at earlier ages, increased risks exist even in cancers of advanced ages. Familial cancers might not be early onset in people whose family members were affected at older ages and so familial cancers might have distinct early and late onset components.
Introduction IGF1 may be important for colorectal cancer risk because of its role in cell growth and differentiation. High IGF1 serum levels have been associated with increased risk of colorectal cancer. Variations in these serum levels have been associated with a CA repeat microsatellite 1 kilobase upstream of the transcription start site. We sought to determine the association of germline variation of the IGF1 gene with colorectal cancer predisposition by performing a large case-control study.
Methods Genescan 500 was used to differentiate alleles of the IGF1 microsatellite among 2143 colorectal cancer cases (enriched for family history) and 1715 controls from the CORGI (COloRectal Gene Identification) study, with subsequent 100% confirmation of about 5% of genotypes by direct sequencing. Associations of genotypes with the following clinicopathological features were tested: sex; site of tumour; Dukes stage; age of onset; presence of adenomas. Using genotype data obtained from the Hap550 platform by colleagues1 plus the genotypes at the insertion/deletion, we reconstructed haplotype blocks around the IGF1 gene in the controls using 68 tagging SNPs.
Results All the alleles confer increased risk for colorectal neoplasia except ‘192′ (192 copies of CA repeat), which is a protective allele (allelic OR for ‘192′ =1.199; 95% CI 1.09 to 1.32; p = 0.000152). The population attributable risk (PAR) for the risk ‘allele’ (ie, where ‘X’=not ‘192′) is 2.94%. The risk alleles occurred more frequently in more advanced Dukes’ stage tumours (p=0.039, χ2). Several SNPs in close linkage disequilibrium with IGF1 are also significantly associated with colorectal neoplasia risk.
Conclusion This study demonstrates a novel association of IGF1 microsatellite with colorectal cancer risk. The association is stronger with advanced stage colorectal cancers, and in colonic rather than rectal cancers. This microsatellite is in linkage disequilibrium with other significant SNPs in the promoter region of this gene.
Gut 2011;60:A116-A117 doi:10.1136/gut.2011.239301.246
Family History of Bowel `Cancer Clinic, West Middlesex University Hospital, London, UK; Cancer Medicine, Imperial College, London, UK; Molecular and Population Genetics, Cancer Research UK, London, UK
Introduction Progressive loss of cell cycle control is an important feature on the adenoma-carcinoma sequence of colorectal cancer. Cyclin-dependent kinase inhibitor 1A (P21/CDKN1A) is an important target of the TGFβ signalling pathway, and it is commonly under-expressed as colorectal neoplasia develop. The aim of this study was to identify low penetrance germline variation in this gene which predisposes individuals to colorectal cancer.
Methods Variation in the coding region of CDKN1A was determined in fifty colorectal cancer cases with a strong family history and 50 controls were tested using the Lightscanner and direct sequencing. 15 tagging SNPs around CDKN1A were typed in the CORGI cases and controls as part of a genome-wide analysis using the Illumina Hap550 platform in 930 cases and 960 controls performed by colleagues (Tomlinson et al 2007). Allele-specific expression of the gene was examined using quantitative reverse transcriptase PCR linked to SNPs in an upstream promoter region.
Results A novel amino-acid changing variant Phe22Leu was identified in a single colorectal cancer patient. Six patients were identified in the case group and 5 in the control group with Arg31Ser. In the association study the two most significant SNPs lie in an upstream promoter region and are in linkage disequilibrium, both are risk alleles for colorectal cancer (OR 1.13; 95% CI 1.06 to 1.2).
p ( χ2)
There were significant differences in expression between CDKN1A and the controls in 94 samples (p=0.037, Student’s t test), demonstrating linkage of these upstream polymorphisms to allele-specific expression of CDKN1A.
Conclusion Rare variants of P21/CDKN1A are an infrequent cause of predisposition to colorectal neoplasia. A promoter region upstream of the CDKN1A is associated with prediposition to colorectal neoplasia, and is linked to allele-specific expression of this gene.
By James Gallagher, Health and science reporter, BBC News Jan 2012
Putting genetic testing at the heart of the NHS could herald a “revolution” in diagnosing, treating and preventing disease, according to the government’s genetics adviser.
Prof Sir John Bell has been presenting a report on how the NHS should prepare for advances in the field.
He said missing out would come at a high cost to patients.
One of the problems with modern medicine is that some of the definitions of disease are too broad.
Prof Bell told the BBC: “Breast cancer has always been defined because it is a tumour in the breast.
“But if you look at the molecular detail of those cancers, some are much more similar to ovarian cancers than they are to other breast cancers, in molecular terms and in terms of their response to therapy.”
Cancer drugs are generally effective in fewer than one in three patients who take them, the report says.
Prof Sir John Bell Chair of Human Genomics Strategy Group
The theory is that by looking at which genes are active inside a tumour, it will be possible to pick the correct treatment.
This is already happening in some cases. Bowel cancer patients with the defective gene K-RAS do not respond to some drugs, while the breast cancer drug herceptin works only if patients have a specific mutation, HER2.
One of the driving forces behind genetics in medicine is the plummeting cost of working out a patient’s genetic code. To sequence one patient’s genome once cost millions of pounds but it now costs thousands, and Prof Bell argues that in the future, the “cost could be essentially nothing”.
Prof Bell has previously accused the NHS of being “completely unprepared” for advances in the field of genetics. He has called for ministers to develop a strategy which would see the NHS adopting genetic tools, and training current and new staff in genetics.
He also wants a national centre which could store genetic information about patients who were sequenced. It would allow doctors to compare mutations in the genetic code with other patients who had the same mutation, to help plan treatment.
Andrew Lansley Health Secretary
Prof Bell acknowledged that reforming the healthcare system to take greater account of genetics would require investment, but he added: “Innovation in any setting has to deliver a much better product or lower cost, or both, and I think genetics may be one of the things that does both.”
The government has yet to formally respond to the recommendations. However, Mr Lansley has announced plans to develop a new way of introducing and funding genetic tests for cancer.
“We want to make sure that all patients can benefit from these tests – as soon as the tests are recommended by NICE (the National Institute for Health and Clinical Excellence),” he said.
He compared the genetic code to a treasure map, saying the Xs were starting to appear, and that the promise of the field was “immense”.
The chief medical officer for England, Prof Dame Sally Davies, said genetics was “terrifically exciting” and would have an “increasingly important role” in areas such as cancer screening.
However, she said she was “quite worried” about some of the consequences, such the possibility that telling patients they had a low risk of developing lung cancer would give them a licence to smoke.
From March, Norwich, South of Tyne, St Mark’s London, Surrey, West Kent and Wolverhampton NHS trusts will offer screening to everyone aged over 55.
The screening involves a thin, bendy tube with a camera attached being placed into the rectum and lower bowel.
Currently, those aged 60-69 in England are offered faecal occult blood tests.
“Over 90% of cases of bowel cancer can be treated successfully if caught in the initial stages”
Mark Flannagan Chief Executive of Beating Bowel Cancer
If any blood is found in the faeces, the person will be invited for further tests – usually a colonoscopy, where a thin, flexible tube with a camera is guided along the entire length of the large bowel.
The new screening will invite younger, symptomless patients to have a similar camera check, a flexible sigmoidoscopy, of the lower part of their large bowel to look for any abnormal growths.
Screening in this way allows doctors to remove growths that might otherwise turn in to cancer and treat any cancers already present.
Mark Flannagan, chief executive of Beating Bowel Cancer, said: “We welcome the government’s commitment to the introduction of flexible sigmoidoscopy as part of the prime minister’s previous pledge which will give patients greater access to diagnostic tests. This is vital if we are to save lives.
“Over 90% of cases of bowel cancer can be treated successfully if caught in the initial stages, so screening is essential to ensure we give patients the best chance of recovery. Bringing in this test has the potential to save thousands of lives through early detection.
“We look forward to playing our part in ensuring a full programme is rolled out across England as quickly as possible so that many more people across the country can benefit.”
About one in 20 people in the UK will develop bowel cancer during their lifetime.
It is the third most common cancer in the UK, and the second leading cause of cancer deaths, with more than 16,000 people dying from it each year.
The plans will be unveiled on Tuesday at the Britain Against Cancer conference, where Mr Hunt is expected to say England has lagged behind other comparable countries in cancer survival league tables for too long.
For some cancer types, survival rates are 10-15% lower in England than in comparable countries such as Australia, Canada and Sweden.
A new £100m project will map the DNA of up to 100,000 patients with cancer and other rare diseases.
The genetic data will help researchers to develop new drugs and tests that could help save thousands of lives.
Britain should “push the boundaries” and become the first country to introduce genetic sequencing to its mainstream health service, according to the prime minister David Cameron.
He said: “Britain has often led the world in scientific breakthroughs and medical innovations, from the first CT scan and test-tube baby through to decoding DNA. By unlocking the power of DNA data, the NHS will lead the global race for better tests, better drugs and above all better care.We are turning an important scientific breakthrough into a potentially life-saving reality for NHS patients across the country.”
He added: “If we get this right, we could transform how we diagnose and treat our most complex diseases not only here but across the world, while enabling our best scientists to discover the next wonder drug or breakthrough technology.”
Dr Harpal Kumar, Cancer Research UK’s chief executive, welcomed the plans: “This work will uncover a wealth of new information which doctors and scientists will use to learn more about the biology of the disease and to develop new ways to prevent, diagnose and effectively treat cancer.
“We’re very excited about personalised medicine – some targeted treatments, such as imatinib, a drug for chronic myeloid leukaemia are already helping to treat patients more effectively – and we’re working hard, with many others – to develop new treatments, and to ensure the NHS can effectively deliver a more personalised cancer treatment service.”
He added: “We hope that this vital investment, together with other measures, such as continued support to diagnose cancers earlier, when treatment is more likely to be successful, will be an important step towards saving more lives from cancer, sooner.
“But, it will be some time before everyone with the disease will be able to have treatment based on the genetic make-up of their cancer.”
The NHS already analyses single genes in cancer tests to determine the chances of particular patients having side-effects from treatment.
Professor Dame Sally Davies, the government’s chief medical officer, explained: “At the moment, these tests focus on diseases caused by changes in a single gene.
“This funding opens up the possibility of being able to look at the three billion DNA pieces in each of us so we can get a greater understanding of the complex relationship between our genes and lifestyle.”
The £100m earmarked from the project, which stems from existing NHS budgets, will be spent on training genetic scientists, mapping patients’s DNA, and creating systems for handling the information.
The Human Genome Project, which made an initial ‘rough draft’ of the human genetic sequence in 2011, cost approximately £500m.
But technological advances have cut costs dramatically, meaning the procedure can now be performed for under £1,000 per person, and officials believe the new £100m DNA mapping investment could reduce prices further still.
All patients will be asked for permission before their DNA is sequenced, with all subsequent data anonymised before it is stored.
Alongside the DNA mapping announcement, the government also allocated £100m of new science funding in the Autumn Statement to the life sciences sector.
The money will help build research capabilities for synthetic biology, facilities for manufacturing cell and biological medicines such as antibodies and vaccines.
Science minister David Willetts said: “Life sciences is one of the most truly international sectors – so if we are to continue to be a world player and compete in the global race we must do everything we can to support it.
“In the past year, our initiatives have attracted more than £1 billion of private sector investment to the UK. We can see clear evidence the UK is succeeding in creating the right environment to attract global investment to our shores and continue to be world leader in life sciences.”
NCHPEG and the American Medical Association (AMA) have released a free Web-based educational program designed to improve the primary care provider’s ability to identify hereditary colorectal cancer syndromes in their patients. This program focuses on case-based learning through a series of clinical scenarios that apply point-of-care tools to key clinical roles in risk assessment, genetic testing, communication, and management. The program also provides access to the point-of-care tools as downloadable pdfs for use in patient care.
“With rapidly developing advances in genetic and molecular medicine, physicians are seeking ways to stay up-to-date in this field to better serve their patients,” said AMA President Jeremy A. Lazarus, M.D. “These developments have made it possible for physicians to now identify hereditary cancer syndromes by looking for specific clues in a patient’s personal and family medical history. We created this educational program to help physicians identify, evaluate, communicate with and manage patients at increased risk for colorectal cancer.”
Colorectal cancer affects approximately 140,000 individuals annually in the U.S. Like other cancers, it develops due to a combination of genetic, biologic and environmental factors interacting together. Approximately 5-10 percent of colorectal cancers are caused by a hereditary syndrome in which a single gene alteration conveys a high risk of colorectal and sometimes other cancers. Individuals suspected to have a hereditary cancer syndrome can sometimes be offered genetic testing to aid in the diagnosis.
“Physicians and other health providers often need information and tools to integrate genetics into their practice,” said NCHPEG Executive Director Joan Scott, M.S., C.G.C. “We developed this program to allow providers to learn as they apply skills through working through cases. They leave the program with knowledge, skills and easily accessible point-of-care tools they can use with their patients.”
This course is available freely available to all users. CME is available in both an enduring, traditional format and a performance improvement format. The enduring format of the course has been certified for 6.0 AMA PRA Category 1 CreditsTM, while participants who complete all three stages of the performance improvement format are eligible for 20.0 AMA PRA Category 1 CreditsTM.
This program was funded by Myriad Genetics, VHA Contract #VA200P0034, AMA, and Humana.
Interested in taking the program? The course is available in both an enduring format and a performance improvement format for CME credit. Individuals who do not plan to apply for CME should register for the enduring course. Click on the links to read more about each option and register.