International Agency for Research on Cancer
International Agency for Research on Cancer
News Article | May 25, 2017
Scientists have found that carrying fat around your middle could be as good an indicator of cancer risk as body mass index (BMI), according to research published in the British Journal of Cancer. It shows that adding about 11cm to the waistline increased the risk of obesity related cancers by 13 per cent. For bowel cancer, adding around 8 cm to the hips is linked to an increased risk of 15 per cent. Carrying excess body fat can change the levels of sex hormones, such as oestrogen and testosterone, can cause levels of insulin to rise, and lead to inflammation, all of which are factors that have been associated with increased cancer risk. This is the first study comparing adult body measurements in such a standardized way for obesity-related cancers. Using a novel approach, scientists at the International Agency for Research on Cancer (IARC-WHO) showed that three different measurements of body size, BMI, waist circumference, and waist to hip ratio all predicted similar obesity-related cancer risk in older adults. The study combined data from around 43,000 participants who had been followed for an average of 12 years and more than 1,600 people were diagnosed with an obesity-related cancer. Dr Heinz Freisling, lead study author and scientist at the International Agency for Research on Cancer (IARC-WHO), said: "Our findings show that both BMI and where body fat is carried on the body can be good indicators of obesity-related cancer risk. Specifically, fat carried around the waist may be important for certain cancers, but requires further investigation." "To better reflect the underlying biology at play, we think it's important to study more than just BMI when looking at cancer risk. And our research adds further understanding to how people's body shape could increase their risk." Being overweight or obese is the single biggest preventable cause of cancer after smoking and is linked to 13 types of cancer including bowel, breast, and pancreatic. Dr Julie Sharp, Cancer Research UK's head of health information, said: "This study further highlights that however you measure it being overweight or obese can increase the risk of developing certain cancers, including breast and bowel. "It's important that people are informed about ways to reduce their risk of cancer. And while there are no guarantees against the disease, keeping a healthy weight can help you stack the odds in your favour and has lots of other benefits too. Making small changes in eating, drinking and keeping physically active that you can stick with in the long term can help you get to a healthy weight -- and stay there."
News Article | May 23, 2017
Scientists have found that carrying fat around your middle could be as good an indicator of cancer risk as body mass index (BMI), according to research* published in the British Journal of Cancer today (Wednesday). It shows that adding about 11cm to the waistline increased the risk of obesity related cancers** by 13 per cent. For bowel cancer, adding around 8 cm to the hips is linked to an increased risk of 15 per cent. *** Carrying excess body fat can change the levels of sex hormones, such as oestrogen and testosterone, can cause levels of insulin to rise, and lead to inflammation, all of which are factors that have been associated with increased cancer risk. This is the first study comparing adult body measurements in such a standardised way for obesity-related cancers. Using a novel approach, scientists at the International Agency for Research on Cancer (IARC-WHO) showed that three different measurements of body size, BMI****, waist circumference, and waist to hip ratio all predicted similar obesity-related cancer risk in older adults. The study combined data from around 43,000 participants who had been followed for an average of 12 years and more than 1,600 people were diagnosed with an obesity-related cancer. Dr Heinz Freisling, lead study author and scientist at the International Agency for Research on Cancer (IARC-WHO), said: "Our findings show that both BMI and where body fat is carried on the body can be good indicators of obesity-related cancer risk. Specifically, fat carried around the waist may be important for certain cancers, but requires further investigation." "To better reflect the underlying biology at play, we think it's important to study more than just BMI when looking at cancer risk. And our research adds further understanding to how people's body shape could increase their risk." Being overweight or obese is the single biggest preventable cause of cancer after smoking and is linked to 13 types of cancer including bowel, breast, and pancreatic. Dr Julie Sharp, Cancer Research UK's head of health information, said: "This study further highlights that however you measure it being overweight or obese can increase the risk of developing certain cancers, including breast and bowel. "It's important that people are informed about ways to reduce their risk of cancer. And while there are no guarantees against the disease, keeping a healthy weight can help you stack the odds in your favour and has lots of other benefits too. Making small changes in eating, drinking and keeping physically active that you can stick with in the long term can help you get to a healthy weight - and stay there." For media enquiries contact Kathryn Ingham in the British Journal of Cancer press office on 020 3469 5475 or, out of hours, on 07050 264 059. * Freisling et al. Comparison of general obesity and measures of body fat distribution in older adults in relation to cancer risk: meta-analysis of individual participant data of seven prospective cohorts in Europe. British Journal of Cancer. Paper: https:/ ** This included people diagnosed with: postmenopausal female breast, colorectal, lower oesophagus, upper stomach, liver, gallbladder, pancreatic, womb, ovary, and kidney. *** The study presents obesity-related cancer risk as the change in risk per standardised unit (standard deviation) in BMI or waist circumference, which allows direct comparisons between these obesity-related cancer risk estimates. Cancer Research UK have used the population estimates of actual BMI and waist circumference presented in the paper to approximate how these changes in obesity-related cancer risk translate to actual BMI and waist circumference. **** Body mass index is calculated with the weight and height of an individual and expressed in units of kg/m2. Healthy weight: 18.5 to 24.9, overweight: 25 to 29.9, obese: over 30. The BJC is owned by Cancer Research UK. Its mission is to encourage communication of the very best cancer research from laboratories and clinics in all countries. Broad coverage, its editorial independence and consistent high standards have made BJC one of the world's premier general cancer journals. http://www.
News Article | May 26, 2017
Overall intracranial response rate (OIRR) in patients with measurable brain metastases was 57% (95% CI: 37, 76; n = 28) for patients treated with Zykadia, versus 22% (95% CI: 9, 42; n = 27) for patients treated with chemotherapy1. The whole body overall response rate (ORR) was 73% (95% CI: 66, 79; n = 187) in patients treated with Zykadia1. "Today's approval represents the next step in the development of Zykadia as a treatment option for ALK-positive metastatic NSCLC, bringing this important medication to a patient population where a need still exists," said Bruno Strigini, CEO, Novartis Oncology. "At Novartis, we are tireless in our pursuit of developing novel medicines to treat lung cancer, and the first-line approval of Zykadia for ALK-positive metastatic NSCLC illustrates our commitment to cancer patients." Approximately 3-7% of all patients with NSCLC have an ALK gene rearrangement2. An FDA-approved test at the time of diagnosis may help to determine the presence of this mutation and, thus, the most appropriate treatment option3. Novartis Commitment to Lung Cancer Worldwide, lung cancer causes more deaths than colon, breast and prostate cancer combined, and an estimated 1.8 million new cases of lung cancer are diagnosed each year4,5. Among patients with NSCLC, roughly 25% have an actionable mutation that may be targeted with available therapies6. Over the past decade, Novartis Oncology's research has supported the evolution of treatment approaches for patients living with mutation-driven types of lung cancer. The company continues its commitment to the global lung cancer community through ongoing studies, as well as the exploration of investigational compounds that target genomic biomarkers in NSCLC. About ASCEND-4 ASCEND-4 is a Phase III randomized, open-label, multicenter, global clinical trial to evaluate the safety and efficacy of Zykadia compared to standard chemotherapy, including maintenance, in adult patients with Stage IIIB or IV ALK-positive advanced NSCLC who received no prior therapy for their advanced disease. Patients received Zykadia orally at 750 mg/daily or standard pemetrexed-based platinum doublet chemotherapy (pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 or carboplatin AUC 5-6) for four cycles followed by pemetrexed maintenance. Of 376 patients, 189 (59 with brain metastases) were randomized to Zykadia and 187 (62 with brain metastases) to chemotherapy1. Approximately 70% of patients with measurable brain metastases at baseline did not have prior radiation therapy, the current standard of treatment for baseline brain metastases1. Among patients randomized to the chemotherapy arm, 43% received Zykadia as their next treatment after platinum-based chemotherapy1. Patients treated with first-line Zykadia had a median PFS of 16.6 months (95% CI: 12.6, 27.2), compared to 8.1 months (95% CI: 5.8, 11.1) for patients treated with standard first-line pemetrexed-platinum chemotherapy with pemetrexed maintenance1. A 45% risk reduction in PFS was obtained in the Zykadia arm compared to the chemotherapy arm (hazard ratio [HR] = 0.55 [95% CI: 0.42, 0.73; one-sided p value <0.0001])1. Patients without brain metastases at screening receiving Zykadia experienced a median PFS of 26.3 months (95% CI: 15.4, 27.7), compared with 8.3 months (95% CI: 6.0, 13.7) among patients treated with chemotherapy (HR = 0.48 [95% CI: 0.33, 0.69])7. Among patients with brain metastases at screening, the median PFS was 10.7 months (95% CI: 8.1, 16.4) in the Zykadia group versus 6.7 months (95% CI: 4.1, 10.6) in the chemotherapy group (HR = 0.70 [95% CI: 0.44, 1.12])7. The most common adverse reactions in ASCEND-4 (incidence ≥25% all grades) were diarrhea (85%), nausea (69%), vomiting (67%), fatigue (45%), abdominal pain (40%), decreased appetite (34%) and cough (25%)1. In ASCEND-4, Grade 3/4 adverse reactions (incidence ≥2%) were fatigue (7%), vomiting (5%), diarrhea (4.8%), abdominal pain (3.7%), weight loss (3.7%), nausea (2.6%) and prolonged QT interval (2.6%)1. The most common laboratory abnormalities in ASCEND-4 (incidence ≥25% all grades) were increased ALT/AST (91%/86%), increased GGT (84%), increased alkaline phosphatase (81%), creatinine increase (77%), anemia (67%), hyperglycemia (53%), decreased phosphate (38%), increased amylase (37%) and neutropenia (27%)1. In ASCEND-4, Grade 3/4 laboratory abnormalities (incidence ≥2%) were increased GGT (49%), ALT/AST (34%/21%), increased alkaline phosphatase (12%), hyperglycemia (10%), increased amylase (8%), increase lipase (6%), creatinine increase (4.2%), anemia (4.2%), decreased phosphate (3.7%) and neutropenia (2.1%)1. About Zykadia Zykadia is an oral, selective inhibitor of anaplastic lymphoma kinase (ALK), a gene that can fuse with others to form an abnormal "fusion protein" that promotes the development and growth of certain tumors in cancers including non-small cell lung cancer (NSCLC). Zykadia is currently approved in over 69 countries worldwide. Please visit https://www.hcp.novartis.com/products/zykadia/ for additional information. Zykadia Important Safety Information Zykadia may cause serious side effects. Zykadia may cause stomach upset and intestinal problems in most patients, including diarrhea, nausea, vomiting and stomach-area pain. These problems can be severe. Patients should follow their doctor's instructions about taking medicines to help these symptoms, and should call their doctor for advice if symptoms are severe or do not go away. Zykadia may cause severe liver injury. Patients should have blood tests prior to the start of treatment with Zykadia, every two weeks for the first month of treatment and monthly thereafter, and should talk to their doctor right away if they experience any of the following symptoms: tiredness (fatigue), itchy skin, yellowing of the skin or the whites of the eyes, nausea or vomiting, decreased appetite, pain on the right side of the abdomen, urine turns dark or brown, or bleeding or bruising more easily than normal. Zykadia may cause severe or life-threatening swelling (inflammation) of the lungs during treatment that can lead to death. Symptoms may be similar to those symptoms from lung cancer. Patients should tell their doctor right away about any new or worsening symptoms, including trouble breathing or shortness of breath, fever, cough, with or without mucous, or chest pain. Zykadia may cause very slow, very fast, or abnormal heartbeats. Doctors should check their patient's heart during treatment with Zykadia. Patients should tell their doctor right away if they feel new chest pain or discomfort, dizziness or lightheadedness, faint, or have abnormal heartbeats, blue discoloration of lips, shortness of breath, swelling of lower limbs or skin, or if they start to take or have any changes in heart or blood pressure medicines. Zykadia may cause high levels of glucose in the blood. People who have diabetes or glucose intolerance, or who take a corticosteroid medicine have an increased risk of high blood sugar with Zykadia. Patients should have glucose blood tests prior to the start of treatment with Zykadia and during treatment. Patients should follow their doctor's instructions about blood sugar monitoring and call their doctor right away with any symptoms of high blood sugar, including increased thirst and/or urinating often. Zykadia may cause high levels of pancreatic enzymes in the blood and may cause pancreatitis. Patients should have blood tests prior to the start of treatment with Zykadia and as needed during their treatment with Zykadia. Patients should talk to their doctor if they experience signs and symptoms of pancreatitis which including upper abdominal pain that may spread to the back and get worse with eating. Before patients take Zykadia, they should tell their doctor about all medical conditions, including liver problems; diabetes or high blood sugar; heart problems, including a condition called long QT syndrome; if they are pregnant, if they think they may be pregnant, or if they plan to become pregnant; are breastfeeding or plan to breastfeed. Zykadia may harm unborn babies. Women who are able to become pregnant must use a highly effective method of birth control (contraception) during treatment with Zykadia and up to 3 months after stopping Zykadia. Patients and their doctor should decide whether to take Zykadia or breastfeed, but should not do both. Patients should tell their doctor about medicines they take, including prescription medicines, over-the-counter medicines, vitamins and herbal supplements. The most common adverse reactions with an incidence of ≥10% diarrhea, nausea, vomiting, liver laboratory test abnormalities, fatigue, abdominal pain, decreased appetite, weight decreased constipation, blood creatinine increased, rash, anemia, and esophageal disorder. Grade 3-4 adverse reactions with an incidence of ≥5% were fatigue, vomiting, diarrhea, abdominal pain, weight loss, nausea, and prolonged QT Interval. Patients should stop taking Zykadia and seek medical help immediately if they experience any of the following, which may be signs of an allergic reaction: Patients should tell their doctor of any side effect that bothers them or does not go away. These are not all of the possible side effects of Zykadia. For more information, patients should ask their doctor or pharmacist. Patients should take Zykadia exactly as their health care provider tells them. Patients should not change their dose or stop taking Zykadia unless their health care provider advises them to. Zykadia should be taken once a day on an empty stomach. Patients should not eat for at least 2 hours before and 1 hour after taking Zykadia. If a dose of Zykadia is missed, they should take it as soon as they remember. If their next dose is due within the next 12 hours, they should skip the missed dose and take the next dose at their regular time. They should not take a double dose to make up for a forgotten dose. Patients should not drink grapefruit juice or eat grapefruit during treatment with Zykadia, as it may make the amount of Zykadia in their blood increase to a harmful level. If patients have to vomit after swallowing Zykadia capsules, they should not take more capsules until their next scheduled dose. Please see full Prescribing Information for Zykadia. Disclaimer The foregoing release contains forward-looking statements that can be identified by words such as "Breakthrough Therapy designation," "next step," "tireless," "commitment," "ongoing," "investigational," or similar terms, or by express or implied discussions regarding potential new indications or labeling for Zykadia, or regarding potential future revenues from Zykadia. You should not place undue reliance on these statements. Such forward-looking statements are based on the current beliefs and expectations of management regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that Zykadia will be submitted or approved for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that Zykadia will be commercially successful in the future. In particular, management's expectations regarding Zykadia could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; the company's ability to obtain or maintain proprietary intellectual property protection; general economic and industry conditions; global trends toward health care cost containment, including ongoing pricing and reimbursement pressures; safety, quality or manufacturing issues, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise. About Novartis Located in East Hanover, NJ Novartis Pharmaceuticals Corporation is an affiliate of Novartis which provides innovative healthcare solutions that address the evolving needs of patients and societies. Headquartered in Basel, Switzerland, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, cost-saving generic and biosimilar pharmaceuticals and eye care. Novartis has leading positions globally in each of these areas. In 2016, the Group achieved net sales of USD 48.5 billion, while R&D throughout the Group amounted to approximately USD 9.0 billion. Novartis Group companies employ approximately 118,000 full-time-equivalent associates. Novartis products are sold in approximately 155 countries around the world. For more information, please visit http://www.novartis.com. Novartis is on Twitter. Sign up to follow @Novartis at http://twitter.com/novartis and @NovartisCancer at http://twitter.com/novartiscancer. For questions about the site or required registration, please contact email@example.com References 1. Zykadia® (ceritinib) Full Prescribing Information. 2. Lovly, C., L. Horn, W. Pao. 2016. Molecular Profiling of Lung Cancer. My Cancer Genome. https://www.mycancergenome.org/content/disease/lung-cancer/. (Updated March 28). Accessed March 22, 2017. 3. Lindeman, N.I., et al. Molecular Testing Guideline for Selection of Lung Cancer Patients for EGFR and ALK Tyrosine Kinase Inhibitors. Arch Pathol Lab Med. 2013; 137: 828-1174. 4. World Health Organization. International Agency for Research on Cancer. GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012. Lung Cancer. Available at http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx?cancer=lung. Accessed March 22, 2017. 5. Riess JW, Wakelee, HA. Metastatic Non-Small Cell Lung Cancer Management: Novel Targets and Recent Clinical Advances. Clinical Advances in Hematology & Oncology. 2012; 10: 226-224. 6. Korpanty, G.J., et al. Biomarkers that currently affect clinical practice in lung cancer: EGFR, ALK, MET, ROS-1, and KRAS. Frontiers in Oncology. 2014; 4: 204. 7. Soria JC, et al. First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): A randomized, open-label Phase 3 study. The Lancet. 2017; 389(10072):917-929. To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/novartis-receives-fda-approval-for-expanded-use-of-zykadia-in-first-line-alk-positive-metastatic-non-small-cell-lung-cancer-nsclc-300464778.html
Torre L.A.,Surveillance and Health Services Research |
Bray F.,International Agency for Research on Cancer |
Siegel R.L.,Surveillance and Health Services Research |
Ferlay J.,International Agency for Research on Cancer |
And 2 more authors.
CA Cancer Journal for Clinicians | Year: 2015
Cancer constitutes an enormous burden on society in more and less economically developed countries alike. The occurrence of cancer is increasing because of the growth and aging of the population, as well as an increasing prevalence of established risk factors such as smoking, overweight, physical inactivity, and changing reproductive patterns associated with urbanization and economic development. Based on GLOBOCAN estimates, about 14.1 million new cancer cases and 8.2 million deaths occurred in 2012 worldwide. Over the years, the burden has shifted to less developed countries, which currently account for about 57% of cases and 65% of cancer deaths worldwide. Lung cancer is the leading cause of cancer death among males in both more and less developed countries, and has surpassed breast cancer as the leading cause of cancer death among females in more developed countries; breast cancer remains the leading cause of cancer death among females in less developed countries. Other leading causes of cancer death in more developed countries include colorectal cancer among males and females and prostate cancer among males. In less developed countries, liver and stomach cancer among males and cervical cancer among females are also leading causes of cancer death. Although incidence rates for all cancers combined are nearly twice as high in more developed than in less developed countries in both males and females, mortality rates are only 8% to 15% higher in more developed countries. This disparity reflects regional differences in the mix of cancers, which is affected by risk factors and detection practices, and/or the availability of treatment. Risk factors associated with the leading causes of cancer death include tobacco use (lung, colorectal, stomach, and liver cancer), overweight/obesity and physical inactivity (breast and colorectal cancer), and infection (liver, stomach, and cervical cancer). A substantial portion of cancer cases and deaths could be prevented by broadly applying effective prevention measures, such as tobacco control, vaccination, and the use of early detection tests. CA Cancer J Clin 2015;65: 87-108. © 2015 American Cancer Society.
Wild C.P.,International Agency for Research on Cancer
Journal of the National Cancer Institute | Year: 2012
Noncommunicable diseases were estimated to claim more than 36 million lives worldwide in 2008. Major contributors to this burden were cardiovascular disease, cancer, chronic respiratory diseases, and diabetes. The United Nations General Assembly held a high-level meeting on noncommunicable diseases in September 2011 for heads of states and governments, conscious of the projected increases in disease incidence, particularly in low- and middle-income countries. This meeting followed the Special Session on HIV/AIDS in 2001, the only other high-level meeting to discuss a health topic and orient the global political agenda toward a growing threat to human development. Proposed strategies for control of noncommunicable diseases focused mainly on the shared risk factors of tobacco, harmful use of alcohol, physical inactivity, and unhealthy diet. However, for cancer, a broader response is required. Notably, the heterogeneity of cancer with respect to its geographical distribution, etiology, and pathology all demand a more nuanced, regional, or even local approach. Preparations for the meeting elicited enormous attention from governments and nongovernmental organizations, but the engagement of the research community was less evident. This commentary calls for the involvement of the cancer research community in response to the further action detailed in the United Nations Political Declaration emanating from the meeting, identifies a number of cancer-specific priorities, including vaccination against hepatitis B virus and human papillomavirus, cervical cancer screening, and early detection of breast cancer, and suggests areas where cancer research can provide the evidence base for cancer control, notably in improving the quality and coverage of cancer registration, elucidating cancer etiology, and evaluating interventions, including their implementation in low-resource health-care settings. Finally, the need for global cooperation in developing a research agenda for low- and middleincome countries is highlighted. © The Author 2009.
Vineis P.,Imperial College London |
Vineis P.,HuGeF Foundation |
Wild C.P.,International Agency for Research on Cancer
The Lancet | Year: 2014
Cancer is a global and growing, but not uniform, problem. An increasing proportion of the burden is falling on low-income and middle-income countries because of not only demographic change but also a transition in risk factors, whereby the consequences of the globalisation of economies and behaviours are adding to an existing burden of cancers of infectious origin. We argue that primary prevention is a particularly effective way to fight cancer, with between a third and a half of cancers being preventable on the basis of present knowledge of risk factors. Primary prevention has several advantages: the effectiveness could have benefits for people other than those directly targeted, avoidance of exposure to carcinogenic agents is likely to prevent other non-communicable diseases, and the cause could be removed or reduced in the long term-eg, through regulatory measures against occupational or environmental exposures (ie, the preventive effort does not need to be renewed with every generation, which is especially important when resources are in short supply). Primary prevention must therefore be prioritised as an integral part of global cancer control.
Jemal A.,Surveillance Research |
Bray F.,International Agency for Research on Cancer |
Center M.M.,Surveillance Research |
Ferlay J.,International Agency for Research on Cancer |
And 2 more authors.
CA Cancer Journal for Clinicians | Year: 2011
The global burden of cancer continues to increase largely because of the aging and growth of the world population alongside an increasing adoption of cancer-causing behaviors, particularly smoking, in economically developing countries. Based on the GLOBOCAN 2008 estimates, about 12.7 million cancer cases and 7.6 million cancer deaths are estimated to have occurred in 2008; of these, 56% of the cases and 64% of the deaths occurred in the economically developing world. Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among females, accounting for 23% of the total cancer cases and 14% of the cancer deaths. Lung cancer is the leading cancer site in males, comprising 17% of the total new cancer cases and 23% of the total cancer deaths. Breast cancer is now also the leading cause of cancer death among females in economically developing countries, a shift from the previous decade during which the most common cause of cancer death was cervical cancer. Further, the mortality burden for lung cancer among females in developing countries is as high as the burden for cervical cancer, with each accounting for 11% of the total female cancer deaths. Although overall cancer incidence rates in the developing world are half those seen in the developed world in both sexes, the overall cancer mortality rates are generally similar. Cancer survival tends to be poorer in developing countries, most likely because of a combination of a late stage at diagnosis and limited access to timely and standard treatment. A substantial proportion of the worldwide burden of cancer could be prevented through the application of existing cancer control knowledge and by implementing programs for tobacco control, vaccination (for liver and cervical cancers), and early detection and treatment, as well as public health campaigns promoting physical activity and a healthier dietary intake. Clinicians, public health professionals, and policy makers can play an active role in accelerating the application of such interventions globally. ©2011 American Cancer Society, Inc.
Plummer M.,International Agency for Research on Cancer
American Journal of Gastroenterology | Year: 2013
A large cross-sectional survey suggests an association between H. pylori gastritis and colonic neoplasms, but the results should be interpreted with caution. © 2013 by the American College of Gastroenterology.
Olivier M.,International Agency for Research on Cancer
Cold Spring Harbor perspectives in biology | Year: 2010
Somatic mutations in the TP53 gene are one of the most frequent alterations in human cancers, and germline mutations are the underlying cause of Li-Fraumeni syndrome, which predisposes to a wide spectrum of early-onset cancers. Most mutations are single-base substitutions distributed throughout the coding sequence. Their diverse types and positions may inform on the nature of mutagenic mechanisms involved in cancer etiology. TP53 mutations are also potential prognostic and predictive markers, as well as targets for pharmacological intervention. All mutations found in human cancers are compiled in the IARC TP53 Database (http://www-p53.iarc.fr/). A human TP53 knockin mouse model (Hupki mouse) provides an experimental model to study mutagenesis in the context of a human TP53 sequence. Here, we summarize current knowledge on TP53 gene variations observed in human cancers and populations, and current clinical applications derived from this knowledge.
Ohgaki H.,International Agency for Research on Cancer |
Kleihues P.,University of Zürich
Clinical Cancer Research | Year: 2013
Glioblastoma is the most frequent and malignant brain tumor. The vast majority of glioblastomas (∼90%) develop rapidly de novo in elderly patients, without clinical or histologic evidence of a less malignant precursor lesion (primary glioblastomas). Secondary glioblastomas progress from low-grade diffuse astrocytoma or anaplastic astrocytoma. They manifest in younger patients, have a lesser degree of necrosis, are preferentially located in the frontal lobe, and carry a significantly better prognosis. Histologically, primary and secondary glioblastomas are largely indistinguishable, but they differ in their genetic and epigenetic profiles. Decisive genetic signposts of secondary glioblastoma are IDH1 mutations, which are absent in primary glioblastomas and which are associated with a hypermethylation phenotype. IDH1 mutations are the earliest detectable genetic alteration in precursor low-grade diffuse astrocytomas and in oligodendrogliomas, indicating that these tumors are derived from neural precursor cells that differ from those of primary glioblastomas. In this review, we summarize epidemiologic, clinical, histopathologic, genetic, and expression features of primary and secondary glioblastomas and the biologic consequences of IDH1 mutations. We conclude that this genetic alteration is a definitive diagnostic molecular marker of secondary glioblastomas and more reliable and objective than clinical criteria. Despite a similar histologic appearance, primary and secondary glioblastomas are distinct tumor entities that originate from different precursor cells and may require different therapeutic approaches. Copyright © 2013 American Association for Cancer Research.