Osteoarthritis and osteoporosis are the two most common age-related chronic disorders of articular joints and skeleton, representing a major public health problem in most developed countries. Apart from being influenced by environmental factors, both disorders have a strong genetic component, and there is now considerable evidence from large population studies that these two disorders are inversely related. Thus, an accurate analysis of the genetic component of one of these two multifactorial diseases may provide data of interest for the other. However, the existence of confounding factors must always be borne in mind in interpreting the genetic analysis. In addition, each patient must be given an accurate clinical evaluation, including family history, history of drug treatments, lifestyle, and environment, in order to reduce the background bias. Here, we review the impact of recent work in molecular genetics suggesting that powerful molecular biology techniques will soon make possible both a rapid accumulation of data on the genetics of both disorders and the development of novel diagnostic, prognostic, and therapeutic approaches.
candidate genes; genetics; multifactorial diseases; osteoporosis; osteoarthritis
Juvenile myelomonocytic leukemia (JMML) is an aggressive childhood myeloproliferative disorder characterized by the overproduction of myelomonocytic cells. JMML incidence approaches 1.2/million persons in the United States (Cancer Incidence and Survival Among Children and Adolescents: United States SEER Program 1975–1995). Although rare, JMML is innately informative as the molecular genetics of this disease implicates hyperactive Ras as an essential initiating event. Given that Ras is one of the most frequently mutated oncogenes in human cancer, findings from this disease are applicable to more genetically diverse and complex adult leukemias. The JMML Foundation (www.jmmlfoundation.org) was founded by parent advocates dedicated to finding a cure for this disease. They work to bring investigators together in a collaborative manner. This article summarizes key presentations from the 2nd International JMML Symposium, on December 7–8, 2007 in Atlanta, GA. A list of all participants is in Supplementary Table.
Juvenile myelomonocytic leukemia (JMML); RAS; PTPN11; NF1; Therapy; Diagnosis
The strain diversity and the population structure of nosocomial Acinetobacter isolated from patients admitted to different hospitals in Florence, Italy, during a 3-year surveillance program, were investigated by amplified fragment length polymorphism (AFLP). The majority of isolates (84.5%) were identified as A. baumannii, confirming this species as the most common hospital Acinetobacter. Three very distinct A. baumannii clonal groups (A1, A2, and A3) were defined. The A1 isolates appeared to be genetically related to the well-characterized European EU II clone. A2 was responsible for three outbreaks which occurred in two intensive care units. Space/time population dynamic analysis showed that A1 and A2 were successful nosocomial clones. Most of the A. baumannnii isolates were imipenem resistant. The genetic determinants of carbapenem resistance were investigated by multiplex PCR, showing that resistance, independently of hospital origin, period of isolation, or clonal group, was associated with the presence of a bla OXA-58-like gene and with ISAba2 and ISAba3 elements flanking this gene. bla OXA-58 appeared to be horizontally transferred. This study showed that the high discriminatory power of AFLP is useful for identification and typing of nosocomial Acinetobacter isolates. Moreover the use of AFLP in a real-time surveillance program allowed us the recognition of clinically relevant and widespread clones and their monitoring in hospital settings. The correlation between clone diffusion, imipenem resistance, and the presence of the blaOXA-58-like gene is discussed.
Diffuse idiopathic skeletal hyperostosis (DISH) is a common systemic disorder characterised by the ossification of the anterior longitudinal spinal ligament involving at least three contiguous vertebrae and by diffuse extraspinal enthesopathies. The condition is associated with the male sex and with advanced age; its aetiology is uncertain, but seems to be related to obesity and diabetes. The most recent studies in archaeological series demonstrated a relation between high social status and the incidence of DISH. The present study examines two cases of DISH found amongst the members of the Medici family buried in the Basilica of San Lorenzo in Florence. The skeletons of the Grand Dukes Cosimo I (1519–1574) and his son Ferdinand I (1549–1609) showed the typical features of the condition. This result is related to the obesity of the Grand Dukes, attested by the written and artistic sources, and to the protein-based alimentation demonstrated by a paleonutritional study, thus furnishing further evidence to the significance of DISH as a life style.
DISH; Morbus Forrestier; Spinal ankylosis; Obesity; Diabetes; Life style; Renaissance
In the metropolitan area of Florence, 62% of major traumas involve powered two wheeler rider and pillion passengers, 10% cyclists, and 7% pedestrians. The urban and extra-urban areas are the most dangerous for the vulnerable road user. In-depth investigations are needed for assessing detailed information on road accidents. This type of study has been very limited in time frame in Italy, and completely absent in the Tuscan region.
Consequently a study called “In-depth Study of road Accident in FlorencE” (In-SAFE) has been initiated.
A network between the Department of Mechanics and Industrial Technologies (University of Florence) and the Intensive Care Unit of the Emergency Department (Careggi Teaching Hospital, Florence) was created with the aim of collecting information about the road accidents. The data collected includes: on-scene data, data coming from examination of the vehicles, kinematics and dynamic crash data, injuries, treatment, and injury mechanisms. Each injury is codified thorough the AIS score, localized by a three-dimensional human body model based on computer tomography slices, and the main scores are calculated. We then associate each injury with its cause and crash technical parameters. Finally, all the information is collected in the In-SAFE database.
Patient mean age at the time of the accident was 34.6 years, and 80% were males. The ISS mean is 24.2 (SD 8.7) and the NISS mean is 33.6 (SD 10.5). The main road accident configurations are the “car-to-PTW” (25%) and “pedestrian run over” (17,9%). For the former, the main collision configuration is “head-on crash” (57%). Cyclists and PTW riders-and-pillions-passengers suffer serious injuries (AIS3+) mainly to the head and the thorax. The head (56.4%) and the lower extremities (12.7%) are the most frequently injured pedestrian body regions.
The aim of the project is to create an in-depth road accident study with special focus on the correlation between technical parameters and injuries. An in-depth investigation team was setup and is currently active in the metropolitan area of Florence.
Twenty-eight serious road accidents involving twenty-nine ICU patients are studied. PTW users, cyclist and pedestrians are the most frequently involved in metropolitan accidents.
In-depth accident database; Injury mechanism; Injury pattern; Biomechanics; Road accident; Injury causes
The Douglas Mental Health University Institute, in collaboration with the McGill Centre for Studies in Aging, organized a two day symposium entitled “Biological Changes Associated with Healthy Versus Pathological Aging” that was held in December 13 and 14, 2007 on the Douglas campus. The symposium involved presentations on current trends in aging and dementia research across several sub-disciplines: genetics, neurochemistry, structural and functional neuroimaging and clinical treatment and rehabilitation. The goal of this symposium was to provide a forum for knowledge-transfer between scientists and clinicians with different specializations in order to promote cross-fertilization of research ideas that would lead to future collaborative neuroscience research in aging and dementia. In this review article we summarize the presentations made by the thirteen international scientists at the symposium and highlight: (i) past research, and future research trends in neuroscience of aging and dementia and (ii) links across levels of analysis that can lead to fruitful transdisciplinary research programs that will advance knowledge about the neurobiological changes associated with healthy aging and dementia.
healthy aging; dementia; hippocampus; prefrontal cortex; amyloid deposition; MRI; volumetry; dopamine
Neuroblastoma is a pediatric tumor of infancy derived from precursor cells of the sympathetic nervous system. Clinicians and researchers in developmental biology and genetics recently met to facilitate meaningful crosstalk and to discuss considerable progress made in the clinical treatment and basic biology of neuroblastoma. For instance, discoveries in familial neuroblastoma have identified genetic aberrations in Phox2b and Alk that predispose to neuroblastoma, while advances in epigenetics and MYCN regulation have also offered insight into neuroblastoma pathogenesis and future treatment. Moreover, novel therapeutic avenues are also being explored, including targeted immunotherapies, and innovative radiotherapeutic and chemotherapeutic approaches. This multi-disciplinary meeting was convened to aid the transfer of new biological findings into the clinic and to use clinical advances to inform the basic biological understanding of this devastating disease.
Neuroblastoma; Neuroblastoma biology; Molecular biology of neuroblastoma
Sleep research in Drosophila is not only here to stay, but is making impressive strides towards helping us understand the biological basis for and the purpose of sleep—perhaps one of the most complex and enigmatic of behaviors. Thanks to over a decade of sleep-related studies in flies, more molecular methods are being applied than ever before towards understanding the genetic basis of sleep disorders. The advent of high-throughput technologies that can rapidly interrogate whole genomes, epigenomes and proteomes, has also revolutionized our ability to detect genetic variants that might be causal for a number of sleep disorders. In the coming years, mutational studies in model organisms such as Drosophila will need to be functionally connected to information being generated from these whole-genome approaches in humans. This will necessitate the development of appropriate methods for interpolating data and increased analytical power to synthesize useful network(s) of sleep regulatory pathways—including appropriate discriminatory and predictive capabilities. Ultimately, such networks will also need to be interpreted in the context of fundamental neurobiological substrates for sleep in any given species. In this review, we highlight some emerging approaches, such as network analysis and mathematical modeling of sleep distributions, which can be applied to contemporary sleep research as a first step to achieving these aims. These methodologies should favorably impact not only a mechanistic understanding of sleep, but also future pharmacological intervention strategies to manage and treat sleep disorders in humans.
Drosophila; disease; distribution; genetics; modeling; networks; sleep
The growth and development of the human skeleton requires an adequate supply of many different nutritional factors. Classical nutrient deficiencies are associated with stunting (e.g. energy, protein, Zn), rickets (e.g. vitamin D) and other bone abnormalities (e.g. Cu, Zn, vitamin C). In recent years there has been interest in the role nutrition may play in bone growth at intakes above those required to prevent classical deficiencies, particularly in relation to optimising peak bone mass and minimising osteoporosis risk. There is evidence to suggest that peak bone mass and later fracture risk are influenced by the pattern of growth in childhood and by nutritional exposures in utero, in infancy and during childhood and adolescence. Of the individual nutrients, particular attention has been paid to Ca, vitamin D, protein and P. There has also been interest in several food groups, particularly dairy products, fruit and vegetables and foods contributing to acid–base balance. However, it is not possible at the present time to define dietary reference values using bone health as a criterion, and the question of what type of diet constitutes the best support for optimal bone growth and development remains open. Prudent recommendations (Department of Health, 1998; World Health Organization/Food and Agriculture Organization, 2003) are the same as those for adults, i.e. to consume a Ca intake close to the reference nutrient intake, optimise vitamin D status through adequate summer sunshine exposure (and diet supplementation where appropriate), be physically active, have a body weight in the healthy range, restrict salt intake and consume plenty of fruit and vegetables.
Bone growth and development; Bone health; Nutritional factors; Dietary and lifestyle recommendations; Bone measurements in children
Rapidly evolving genetic and genomic technologies for genetic cancer risk assessment (GCRA) are revolutionizing our approach to targeted therapy and cancer screening and prevention, heralding the era of personalized medicine. Although many academic medical centers provide GCRA services, most people receive their medical care in the community setting. Yet, few community clinicians have the knowledge or time needed to adequately select, apply and interpret genetic/genomic tests. This article describes alternative approaches to the delivery of GCRA services, profiling the City of Hope Cancer Screening & Prevention Program Network (CSPPN) academic and community-based health center partnership as a model for the delivery of the highest quality evidence-based GCRA services while promoting research participation in the community setting.
Growth of the CSPPN was enabled by information technology, with videoconferencing for telemedicine and web conferencing for remote participation in interdisciplinary genetics tumor boards. Grant support facilitated the establishment of an underserved minority outreach clinic in the regional County hospital. Innovative clinician education, technology and collaboration are powerful tools to extend GCRA expertise from a NCI-designated Comprehensive Cancer Center, enabling diffusion of evidenced-base genetic/genomic information and best practice into the community setting.
cancer genetics; community; genetic counseling; genetic education; personalized medicine
Osteoporosis and osteoarthritis are age-related disorders of the skeleton with genetic components. Low bone density is a risk factor for osteoporotic fracture while osteoarthritis is associated with increased bone density. The 1,25-dihydroxyvitamin D3 receptor (VDR) gene locus was previously found to be associated with bone density. We therefore studied the relationship between radiographic osteoarthritis at the knee and VDR genotype in a population-based sample (n = 846), using molecular haplotyping of anonymous intragenic DNA polymorphisms. Radiographic osteoarthritis was defined using the Kellgren score, which is based on the assessment of osteophytes and joint space narrowing (JSN). We show that one VDR haplotype allele is significantly overrepresented in individuals with knee osteoarthritis and associated with a 2.27-fold increased relative risk (95% confidence interval 1.46, 3.52). Adjustment for bone density at the femoral neck did not change these results, indicating that the association is not mediated by bone density. The association appeared to be largely explained by the presence of osteophytes rather than JSN. Our results indicate a role of the VDR gene in the pathogenesis of osteophytes while linkage disequilibrium with another nearby gene, i.e., the collagen type IIa1 gene encoding the most abundant protein in cartilage, might contribute to the association.
The International Symposium "Peripheral Nerve Repair and Regeneration and 2nd Club Brunelli Meeting" was held on December 4-5, 2009 in Turin, Italy (Organizers: Bruno Battiston, Stefano Geuna, Isabelle Perroteau, Pierluigi Tos). Interest in the study of peripheral nerve regeneration is very much alive because complete recovery of nerve function almost never occurs after nerve reconstruction and, often, the clinical outcome is rather poor. Therefore, there is a need for defining innovative strategies for improving the success of recovery after nerve lesion and repair and this meeting was intended to discuss, from a multidisciplinary point of view, some of today's most important issues in this scientific field, arising from both basic and clinical neurosciences.
The Annual San Antonio Breast Cancer Symposium is one of the largest regular conferences devoted to breast cancer research and treatment. In particular, it provides a forum in which to discuss the more translational aspects of current basic research, and the 2002 meeting was no exception. Growth factor pathways and endocrine resistance, cancer genomics and the clinical applications of proteomics were three of the major topics for discussion. Presentations on genetic susceptibility and the development of prognostic and predictive markers also created much interest.
BRCA 1/2; cDNA microarray; growth factor pathways; prognostic and predictive markers; proteomics
The Worldwide Innovative Networking (WIN) consortium is a global alliance of academic and industrial cancer researchers, clinicians, and cancer advocacy groups set up to promote innovations in personalised cancer therapy and to accelerate the translation of research in this discipline into the oncology clinic. One of its most important initiatives is the WIN symposia, which have been held in Paris each summer since 2009. The fifth WIN symposium, which was held 10–12 July 2013, took as its overall theme ‘Personalised Cancer Therapy: From Innovation to Implementation’.
Over 400 delegates, including a good number of representatives of patient groups as well as leading academic, industrial, and clinical scientists; students; and post-docs attended this symposium. Its scientific programme featured thirty presentations divided into four main plenary sessions, and there was also a wide-ranging poster session that encompassed all the topics covered in the plenaries.
The programme structure followed the path of drug discovery, in that the first session covered assay development for personalised cancer medicine; the second, applications of genomics in oncology; the third, clinical development; and the fourth, the impact of personalised medicine on cancer care.
biomarkers; personalised medicine; targeted therapy; genomics; proteomics
Traumatic brain injury (TBI) initiates a cascade of numerous pathophysiological
events that evolve over time. Despite the complexity of TBI, research aimed at
therapy development has almost exclusively focused on single therapies, all of
which have failed in multicenter clinical trials. Therefore, in February 2008
the National Institute of Neurological Disorders and Stroke, with support from
the National Institute of Child Health and Development, the National Heart,
Lung, and Blood Institute, and the Department of Veterans Affairs, convened a
workshop to discuss the opportunities and challenges of testing combination
therapies for TBI. Workshop participants included clinicians and scientists from
a variety of disciplines, institutions, and agencies. The objectives of the
workshop were to: (1) identify the most promising combinations of therapies for
TBI; (2) identify challenges of testing combination therapies in clinical and
pre-clinical studies; and (3) propose research methodologies and study designs
to overcome these challenges. Several promising combination therapies were
discussed, but no one combination was identified as being the most promising.
Rather, the general recommendation was to combine agents with complementary
targets and effects (e.g., mechanisms and time-points), rather than focusing on
a single target with multiple agents. In addition, it was recommended that
clinical management guidelines be carefully considered when designing
pre-clinical studies for therapeutic development. To overcome the challenges of
testing combination therapies it was recommended that statisticians and the U.S.
Food and Drug Administration be included in early discussions of experimental
design. Furthermore, it was agreed that an efficient and validated screening
platform for candidate therapeutics, sensitive and clinically relevant
biomarkers and outcome measures, and standardization and data sharing across
centers would greatly facilitate the development of successful combination
therapies for TBI. Overall there was great enthusiasm for working
collaboratively to act on these recommendations.
clinical trials; head injury; injury mechanisms; intervention; in-vitro and in-vivo models
To familiarize the chiropractic clinician with the clinical presentation, radiographic features, and conservative versus surgical treatment options for managing femoroacetabular impingement (FAI) syndrome.
FAI syndrome is a relatively new clinical entity to be described in orthopedics, and has been strongly linked with pain and early osteoarthritis of the hip in young adults. Hip joint radiographs in these patients often appear normal at first—particularly if the clinician is unfamiliar with FAI. The role of conservative therapy in managing this disorder is questionable. Surgical treatment ultimately addresses any acetabular labral or articular cartilage damage, as well as the underlying osseous abnormalities associated with FAI. The most commonly used approach is open surgical hip dislocation; however, more recent surgical procedures also involve arthroscopy.
In FAI syndrome—a condition unknown to many clinicians (including medical)—chiropractors can play an important role in its diagnosis and referral for appropriate management.
acetabulum/abnormalities; femoral neck/abnormalities; osteoarthritis; hip joint; acétabulum/anormalités; col fémoral/anormalités; arthrose; articulation de la hanche
Risk of lung cancer related to region of birth in Italy was investigated among migrants to Florence, in a case control study of all histologically confirmed incident cases of primary lung cancer in a three year period in that city (n = 376). Controls (n = 892) were patients in the same hospital of similar age, sex, date of admission, and smoking status with discharge diagnoses other than lung cancer or suicide. Information on place of birth and year of migration to Florence was collected directly from each subject, along with a detailed occupational history. Logistic regression models were used to calculate the odds ratio for birth in the south of Italy relative to birth elsewhere. Male migrants from the south have an odds ratio of lung cancer of 0.5 (95% limits 0.3 to 0.7) relative to those born elsewhere. This "protective effect" is not explained by smoking or by any known occupational risk. The risk is lowest among those born on the island of Sicily (odds ratio 0.2 compared to those born in the centre-north).
Osteoarthritis (OA), one of the most common age-related chronic disorders of articular cartilage, joints, and bone tissue, represents a major public health problem. Genetic studies have identified multiple gene variations associated with an increased risk of OA. These findings suggest that there is a large genetic component to OA and that the disorder belongs in the multigenetic, multifactorial class of genetic diseases. Studies of chondrodysplasias and associated hereditary OA have provided a better understanding of the role of structural genes in the maintenance and repair of articular cartilage, in the regulation of chondrocyte proliferation and gene expression, and in the pathogenesis of OA.
cartilage; chromosomes; genetics; linkage; osteoarthritis
To develop a collaborative approach for the treatment of gastrointestinal carcinoid tumours and carcinoid syndrome.
Leaders in the medical, endocrine, radiologic and surgical treatment of carcinoid disease were selected to present papers at the Carcinoid Syndrome Symposium on Treatment Modalities for Gastrointestinal Carcinoid Tumours and participate in the workshop that followed.
A multidisciplinary symposium with experts in the field of carcinoid syndrome was organized at the University of Calgary. Data presented, participation of the attendees and a review of the literature were used in the workshop to develop a collaborative approach to the management of carcinoid tumours.
Carcinoid tumours are rare and few centres have large experiences in their treatment. Before the development of this collaboration, patients with carcinoid tumours received a unidisciplinary approach depending on referral patterns. The development of a multidisciplinary neuroendocrine clinic helped to unify the approach to these patients, yet a consensus on the treatment of carcinoid tumours was lacking. The expertise at the symposium allowed for consensus and the development of treatment algorithms, including biochemical screening, radiographic localization and surgical intervention, for gastrointestinal carcinoid tumours. The role of medical and hormonal therapy after cytoreducion is presented.
Patients with carcinoid tumours require a multidisciplinary approach to their care.
The Second Annual Symposium of the Global Cancer Genomics Consortium (GCGC) was held at the Tata Memorial Center in Mumbai, India, from November 19 to 20, 2012. Founded in late 2010, the GCGC aims to provide a platform for highly productive, collaborative efforts on next-generation cancer research through bridging the latest scientific and technology developments with clinical oncology challenges. This year’s presenters brought together highly innovative interdisciplinary views and strategies to meet major challenges in cancer research. The symposium featured 3 major themes: OMICS approaches toward the identification of cancer molecular drivers, single-cell analysis in cancer, and clinical and translational genomics. Each theme was represented in presentations of new findings, with an obvious implication in cross-disciplinary components of OMICs and an overwhelming participation by students. In summary, the GCGC symposium provided a discussion and congregation of the latest advances in basic and translational cancer research and offered the participants with a highly cooperative network environment for future collaboration.
genomics medicine; anticancer target; cancer therapy
A symposium on primary vitreoretinal lymphoma held at the Fifth Annual, National Cancer Institute–sponsored International Primary Central Nervous System Lymphoma Collaborative Group conference, a multidisciplinary meeting, is summarized herein. Tumor biology, nomenclature, epidemiology and prognosis, biology and pathogenesis, animal models, clinical manifestations, diagnosis, therapeutics, and future investigations are reviewed.
Primary vitreoretinal lymphoma (PVRL), also known as primary intraocular lymphoma, is a rare malignancy typically classified as a diffuse large B-cell lymphoma and most frequently develops in elderly populations. PVRL commonly masquerades as posterior uveitis and has a unique tropism for the retina and central nervous system (CNS). Over 15% of primary CNS lymphoma patients develop intraocular lymphoma, usually occurring in the retina and/or vitreous. Conversely, 65%–90% of PVRL patients develop CNS lymphoma. Consequently, PVRL is often fatal because of ultimate CNS association. Current PVRL animal models are limited and require further development. Typical clinical findings include vitreous cellular infiltration (lymphoma and inflammatory cells) and subretinal tumor infiltration as determined using dilated fundoscopy, fluorescent angiography, and optical coherent tomography. Currently, PVRL is most often diagnosed using both histology to identify lymphoma cells in the vitreous or retina and immunohistochemistry to indicate monoclonality. Additional adjuncts in diagnosing PVRL exist, including elevation of interleukin-10 levels in ocular fluids and detection of IgH or T-cell receptor gene rearrangements in malignant cells. The optimal therapy for PVRL is not defined and requires the combined effort of oncologists and ophthalmologists. PVRL is sensitive to radiation therapy and exhibits high responsiveness to intravitreal methotrexate or rituximab. Although systemic chemotherapy alone can result in high response rates in patients with PVRL, there is a high relapse rate. Because of the disease rarity, international, multicenter, collaborative efforts are required to better understand the biology and pathogenesis of PVRL as well as to define both diagnostic markers and optimal therapies.
The osteoarthritic diseases are common disorders characterized by progressive destruction of the articular cartilage in the joints, and associated with remodeling of the subchondral bone, synovitis and the formation of bone outgrowths at the joint margins, osteophytes. From the clinical perspective, osteoarthritis leads to joint pain and loss of function. Osteoarthritis is the leading cause of progressive disability. New data from genetic, translational and basic research have demonstrated that pathways with essential roles in joint and bone development also contribute to the postnatal homeostasis of the articular cartilage and are involved in osteoarthritis, making these potential therapeutic targets. Other systems of interest are the tissue-destructive enzymes that break down the extracellular matrix of the cartilage as well as mediators of inflammation that contribute to synovitis. However, the perspective of a durable treatment over years to decades highlights the need for a personalized medicine approach encompassing a global view on the disease and its management, thereby including nonpharmaceutical approaches such as physiotherapy and advanced surgical methods. Integration of novel strategies based on their efficacy and safety with the identification of individuals at risk and optimal individual rehabilitation management remains a major challenge for the medical community in particular, as the incidence of osteoarthritis is likely to further increase with the overall aging of the population.
Nephrolithiasis is a very common disease with an increasing prevalence among industrialized populations. Kidney stone formation is a complex phenomenon, involving genetic and metabolic patterns, and nutrition can play an important role in this match both as a promoter or as a protective factor. To promote a deeper knowledge of such a challenging disease, clinicians and researchers have met in Rome, Italy, last March 2013, at the International Congress “Nephrolithiasis: a systemic disorder” to discuss patho-physiology and possible treatment of kidney stones. During the meeting, a whole session was dedicated to nutrition, seen both as a cause or a therapeutic tool for nephrolithiasis. Due to its etiopathogenesis, nephrolithiasis is also an ideal model for a nutrigenetics and nutrigenomics approach. Nutrigenomics and nutrigenetic respectively study the effects of a dietary treatment on gene expression and, on the other hand, the impact of an inherited trait on the response to a specific dietary treatment.
Patients diagnosed with breast cancer are often treated with surgery followed by radiation therapy. In this paper, we evaluate the effect that radiotherapy may have had on the subsequent risk of second malignancies, including the possible influences of age at treatment and menopausal status.
In order to evaluate the long-term consequences of radiotherapy, a cohort study was conducted based on clinical records for 5,248 women treated for breast cancer in Florence (Italy), with continuous follow-up from 1965 to 1994. The Cox proportional hazards model for ungrouped survival data was used to estimate the relative risk for second cancer after radiotherapy.
This study indicated an increased relative risk of all second cancers combined following radiotherapy (1.22, 95% CI: 0.88 to 1.69). The increased relative risk appeared five or more years after radiotherapy and appeared to be highest amongst women treated after the menopause (1.61, 95% CI: 1.13 to 2.29). Increased relative risks were observed specifically for leukaemia (8.13, 95% CI: 0.96 to 69.1) and other solid cancers (1.84, 95% CI: 1.06 to 3.16), excluding contralateral breast cancer. For contralateral breast cancer, no raised relative risk was observed during the period more than five years after radiotherapy.
The study indicated a raised risk of second malignancies associated with radiotherapy for breast cancer, particularly for women treated after the menopause.