Incidence Of Bone Cancer Research Articles

Trends in primary malignant bone cancer incidence and mortality in the United States, 2000–2017: A population-based study

BackgroundPrimary malignant bone cancers have extremely low incidence, resulting in poor evaluation of their epidemiological characteristics. The objective of this study was to investigate trends in the incidence of primary malignant bone cancers and related mortality. Materials and methodsData from patients diagnosed with malignant bone cancers from 2000 to 2017 in the Surveillance Epidemiology and End Results database were retrospectively analyzed. Annual age-adjusted incidence and mortality were calculated, and the annual percentage change analyzed. Further, characteristics including patient age and sex, as well as the primary site and stage of different tumor types, were analyzed. ResultsThe overall age-adjusted incidence rate of primary malignant bone cancers was 7.70 per million people per year, and incidence rates had increased in patients between 60 and 79 years old, or with tumor size ≥ 8 cm. The incidence of chordoma increased significantly (annual percentage change (APC), 3.0 % per year), while those of WHO grade I and II primary bone cancers decreased. During 2000–2017, the mortality rate attributable to malignant bone cancers across the entire United States was 4.41 per million people per year. A positive mortality trend was observed during the study period (APC = 0.7 %, 95 % confidence interval: 0.0 %–1.5 %). Patients with osteosarcoma, and those who were female or of white ethnicity showed significant increasing trends in mortality rate. ConclusionsDifferent tumor types have variable epidemiological manifestations, in terms of incidence and mortality, and exhibited altered trends over recent years. These variables can provide guidance to inform allocation of medical resources.

Loss of RanGAP1 drives chromosome instability and rapid tumorigenesis of osteosarcoma.

Chromothripsis is a catastrophic event of chromosomal instability that involves intensive fragmentation and rearrangements within localized chromosomal regions. However, its cause remains unclear. Here, we show that reduction and inactivation of Ran GTPase-activating protein 1 (RanGAP1) commonly occur in human osteosarcoma, which is associated with a high rate of chromothripsis. In rapidly expanding mouse osteoprogenitors, RanGAP1 deficiency causes chromothripsis in chr1q, instant inactivation of Rb1 and degradation of p53, consequent failure in DNA damage repair, and ultrafast osteosarcoma tumorigenesis. During mitosis, RanGAP1 anchors to the kinetochore, where it recruits PP1-γ to counteract the activity of the spindle-assembly checkpoint (SAC) and prevents TOP2A degradation, thus safeguarding chromatid decatenation. Loss of RanGAP1 causes SAC hyperactivation and chromatid decatenation failure. These findings demonstrate that RanGAP1 maintains mitotic chromosome integrity and that RanGAP1 loss drives tumorigenesis through its direct effects on SAC and decatenation and secondary effects on DNA damage surveillance.

International patterns and trends of childhood and adolescent cancer, 1978-2012

BackgroundThis study aimed to provide a detailed analysis of the temporal trends of cancer incidence rates for individuals aged 0–19 years in selected regions globally from 1978 to 2012. MethodsData were obtained from Volumes V-XI of Cancer Incidence in Five Continents (CI5), published by the International Agency for Research on Cancer. A total of 53 registries in 23 regions from the Americas, Asia, Europe, and Oceania that contained information on cancer incidence throughout 1978-2012 (35 years) were included in this study. Joinpoint regression was used for the analysis of trends. ResultsMost regions showed increasing trends in overall childhood cancer among children (aged 0-14 years) and adolescents (aged 15-19 years). Nearly all regions showed rising trends in childhood and adolescent leukemia incidence rates, whereas the incidence of lymphoma among children generally decreased. Only France, Australia, and New Zealand showed decreasing trends for malignant central nervous system (CNS) tumors among adolescents. Kidney cancer and bone cancer incidence rates remained stable for most regions. The incidence of thyroid cancer among adolescents increased in most regions and that of testicular cancer decreased in approximately one-half of the regions studied. ConclusionThe international temporal trends of cancer incidents among children and adolescents are varied by region, cancer type, age group, and gender, and have changed over time.

Bone Cancer Incidence, Mortality, and Trends in Rural and Urban China

Background: Studies on bone cancer (BC) in the Chinese population are few, as BC is rare. Herein, we analyzed the incidence and mortality rates of BC in China using data from the National Central Cancer Registry of China (NCCRC), 2015. And for the first time, the incidence and mortality trends of bone cancer from 2000 to 2015 were studied. Methods: In 2019, 501 cancer registries from 31 provinces in China submitted the 2015 data to the NCCRC, including 173 cities (i.e., urban areas) and 328 counties and county-level areas (i.e., rural areas). The age-standardized incidence and mortality rates, cumulative risk of cancer development before the age of 75 years, and trends were measured. Results: In 2015, 24,200 cases of primary BC and 17,900 associated deaths were recorded in China. The crude incidence of BC was 1.77/100,000. Age-standardized incidence rate in world populations was 1.32/100,000. The crude mortality rate was 1.31/100,000, and age-standardized mortality rate in the world populations was 0.89/100,000. The age-specific incidence and mortality curves were bimodally distributed with age. Male patients had higher crude and age-standardized incidence and mortality rates than female patients. Morbidity and mortality rates were higher in rural areas than in cities. The age-standardized incidence and mortality of BC decreased annually by 2.2% (95% confidence interval [CI], 1.4% to 3.0%) and 4.8% (95% CI, 3.9% to 5.7%), respectively. Conclusions: Primary BC was more common in men than in women and followed a bimodal distribution with age. The age-standardized incidence and mortality of BC have shown downward trends since 2000. Funding Statement: National Key RD CAMS Innovation Fund for Medical Sciences (CIFMS) (2018-I2M-3-003)]. Declaration of Interests: The authors have no conflicts of interest to declare.

Bone cancer incidence by morphological subtype: a global assessment.

To better understand the relevance of environmental factors to the changing patterns of bone cancer subtypes, we examine the incidence of osteosarcoma (OS), Ewing sarcoma (ES), and chondrosarcoma (CS) using data from cancer incidence in five continents. Age-specific and age-standardized incidence rates (ASRs) per 100,000 person-years were computed and stratified by country (n=43), subtype, and sex during 2003-2007. Temporal patterns of ASRs were examined during 1988-2007 (12 countries). Age-period-cohort models were fitted for the USA and UK by subtype. For most countries, OS represented 20-40% of all bone cancers, ES<20%, while CS proportions varied more considerably. Overall ASRs of bone cancers were 0.8-1.2/100,000 in men and 0.5-1.0 in women (0.20-0.35/100,000 for OS and 0.10-0.30/100,000 for CS in both men and women, and <0.10-0.25/100,000 in men and 0.05-0.25/100,000 in women for ES). The age-specific incidence rates revealed a bimodal peak of OS, one peak of ES in childhood, and a more heterogeneous pattern for CS. The overall bone cancer incidence trends are generally flat, but more heterogeneous for ES and CS. A declining OS incidence was observed in the UK and USA (men), an increase in CS in the UK and USA (female), and an apparent increase in ES, followed by a leveling off in successive US and UK cohorts. Monitoring bone cancer incidence trends with data assembled from a geographically broader range of registries may generate hypotheses about additional risk factors and ensure that high-risk populations are not overlooked in cancer control efforts.

Incidence patterns of primary bone cancer in taiwan (2003-2010): a population-based study.

BackgroundPrimary bone cancer (BC) incidence by age has not been surveyed in Asia. MethodsThe incidence patterns of nine subtypes of primary BCs registered between 2003 and 2010 were analyzed from Taiwan cancer registry data. More specific analyses were conducted within age groups (Group I: 0–24 years; Group II: 25–59 years; and Group III: 60–85+ years). ResultsA total of 1,238 newly diagnosed subjects were registered with an age-standardized incidence rate (ASR) of 6.70 per million person-years. Overall, osteosarcoma (OS: 45 %) was the most common, followed by chondrosarcoma (CS: 18 %), and Ewing sarcoma (ES: 8 %). The percentages of cases and ASRs for age groups I, II, and III were 36.3, 43.0, and 20.7 %, and 7.00, 5.48, and 10.28 per million, respectively. Significant male predilections were observed for all BCs combined, and the CS, chordoma, and malignant ameloblastoma subtypes. Our findings demonstrated an upward trend of 4.8 % per year over the study period, and was more significant for females (6.7 %). A significant increase in trend existed in the incidence of BC among females in Group II, and the incidence of OS and ES among females in Group I.ConclusionsThis population-based study has allowed us to confidently define the incidence rates among three age groups of Taiwanese. Despite overall low rates, the upward trend in BC incidence among females may invoke a concern. The results suggest areas for further study into the underlying causes for these cancer trends.

Age-Period-Cohort Analysis of Primary Bone Cancer Incidence Rates in the United States (1976–2005)

Primary bone cancer comprises three major histologic types: osteosarcoma (OS), Ewing sarcoma (ES), and chondrosarcoma (CS). Given the limited knowledge about the etiology of primary bone cancer, we undertook an age-period-cohort (APC) analysis to determine whether incidence varied by birth cohort or calendar period. The purpose was to examine the temporal development of each bone cancer type and generate etiologic hypotheses via the observed birth cohort-related changes. An APC model was fitted to incidence data for U.S. whites for OS, ES, and CS obtained from nine registries of the Surveillance, Epidemiology, and End Results program, which covers about 10% of the U.S. population, 1976-2005. The incidence of OS decreased between 1976 and 2005 among those aged over 60 years, a decline that occurred among patients with OS as their primary malignancy only. From 1986-1995 to 1996-2005, the incidence rate of CS among females of 20 to 69 years rose by about 50%, with rates increasing among consecutive cohorts born during 1935-1975. CS rates among males were stable, as were rates of ES. The risk reduction in OS as a primary malignancy at older ages could possibly be related to diminished exposure over time to bone-seeking radionuclides. The CS increase among females corresponds to birth cohorts with rising exposures to oral contraceptives and menopausal hormonal therapy. As the estrogen signaling pathway has been shown to stimulate proliferation of normal and malignant chondrocytes, estrogen exposure may increase the risk for CS. Further studies are warranted to clarify its possible etiological significance.

A novel locus for canine osteosarcoma (OSA1) maps to CFA34, the canine orthologue of human 3q26

Spontaneous tumors in dogs share many of the same features of their human orthologues including clinical behavior, response to treatment, and molecular defects. It is therefore natural to consider the use of dogs and their spontaneous malignancies in the study of complex disease such as cancer. Scottish Deerhounds are a giant breed of dogs that exhibit a high incidence of bone cancer. Our previous work suggested that osteosarcoma within this breed could be explained by the presence of a major gene of dominant effect. Herein, we use a whole genome mapping approach to evaluate a four-generation pedigree of Scottish Deerhounds for linkage of their osteosarcoma phenotype. Using this approach we found evidence of linkage ( Z max = 5.766) between their phenotype and markers located on CFA34, in a region syntenic to human chromosome 3q26. The identification of this locus provides novel insight into the genetic basis of osteosarcoma in both canines and humans.

Abstract 1822: Age-period-cohort (APC) analysis of primary bone cancer incidence rates in the United States (1976 – 2005)

Abstract BACKGROUND: Primary bone cancer comprises three major histological subtypes: osteosarcoma (OS), Ewing sarcoma (ES) and chondrosarcoma (CS). The most frequent subtype, OS, primarily occurs in adolescence, but has a second peak at the oldest ages, usually attributed to late effects of radiotherapy and chemotherapy, and Paget's disease. The adolescent age distribution of ES resembles that of OS, suggesting a link between the onset of puberty and these subtypes of bone cancer. CS is rare in childhood, and incidence rates, unlike those of OS and ES, increase fairly uniformly with age. Given the limited knowledge about the etiology of primary bone cancer, and the unusual age-incidence distribution for OS and ES, we undertook an APC analysis to determine whether incidence varied by birth cohort or calendar period. For other cancers, such as testis and breast, the identification of cohort patterns has generated new hypotheses regarding environmental risk factors. METHODS: We fit an APC model to incidence data among U.S. whites for OS, ES and CS obtained from nine registries of the Surveillance, Epidemiology, and End Results (SEER) program, which covers about 10% of the U.S. population, 1976-2005. The purpose was to examine the temporal development of each bone cancer subtype, with an aim to providing etiologic clues as to the role of birth cohort-related changes. RESULTS: Incidence of OS decreased between 1976 and 2005 among those 60 years and older, and rates declined among cohorts born 1905-34. The risk of CS doubled among females 20-69 years, with rates increasing among consecutive birth cohorts born 1925-54, whereas those of males were unaltered. For both sexes, ES incidence rates tended to be stable. CONCLUSIONS: The risk reduction in OS at older ages was most likely due to improved radiotherapy and more effective chemotherapy. The CS risk increase in females corresponds to birth cohorts who were increasingly exposed to estrogens, both in terms of contraceptives (from 1960 onwards), and hormone replacement therapy (from 1950 onwards). In support of our hypothesis that estrogens are involved in the increase in CS among women over time, in vitro studies show that the estrogen signaling pathway stimulates proliferation of both normal and malignant chondrocytes. Further studies are warranted to pursue the possible etiological significance of estrogen exposure in CS risk. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1822.

Cancer incidence among refinery and petrochemical employees in Louisiana, 1983-1999.

The purpose of this study is to determine the incidence of cancer among employees at two petrochemical facilities in south Louisiana, and to compare their cancer rates to those of the general population of south Louisiana. Records on 4639 active and former employees and retirees from the two plants were linked to the Louisiana Tumor Registry (LTR) database by LTR staff to ascertain incident cases of cancer. Standardized incidence ratios (SIRs) were then calculated using the south Louisiana population as the comparison and adjusted for age, race, and time period. There was a significant 16% deficit of overall cancer cases for males in this cohort (SIR=0.84; 95% CI, 0.74-0.95). The only significantly elevated SIR in males was for cancer of the bone and joint (SIR=6.89; 95% CI, 1.42-20.1). This result was based on three non-fatal cases of bone cancer with different histologies, occurring in different parts of the body. These cases worked in different units of one plant. Significant deficits were seen for lung cancer, non-Hodgkin's lymphoma, and cancer of the oral cavity and pharynx. Cancer incidence among 719 female employees was non-significantly increased (SIR=1.24; 95% CI, 0.81-1.82). Breast cancer accounts for the excess (SIR=1.46; 95% CI, 0.73-2.61). Seventy percent of the breast cancer cases worked in an office setting. This study found little evidence of any association between cancer incidence and employment at these two petrochemical facilities. The increased incidence of bone cancer is unlikely to be due to occupational exposures. The non-significant excess of breast cancer may be due to early detection or other important unmeasured confounders, such as certain reproductive factors.

Radiotherapy, Alkylating Agents, and Risk of Bone Cancer After Childhood Cancer

Individuals who had cancer in childhood are at higher risk of developing bone cancer than any other type of second primary cancer. Using the population-based National Registry of Childhood Tumours in Britain, we investigated the incidence and etiology of second primary bone cancer after childhood cancer in a cohort study and in a case-control study. A cohort study of 13,175 3-year survivors of childhood cancer diagnosed in Britain between 1940 and 1983 revealed 55 subsequent bone cancers. A largely nested case-control study comprised 59 case subjects developing second primary bone cancer, and 220 control subjects were selected and matched for sex, type of first cancer, age at first cancer, and interval between diagnosis of first cancer and subsequent bone cancer. Outcome measures were the incidence of bone cancer after childhood cancer, the cumulative dose of radiation received at the site of the second cancer in the case subject and at the corresponding anatomic site in the matched control subjects, and the cumulative dose of alkylating agents and vinca alkaloids received by case and control subjects. The percentage of 3-year survivors developing bone cancer within 20 years did not exceed 0.9%, except following heritable retinoblastoma (7.2%), Ewing's sarcoma (5.4%), and other malignant bone tumors (2.4%). The risk of bone cancer increased substantially with increased cumulative dose of radiation to the bone (P< .001, linear trend). At the highest levels of exposure, however, the risk appeared to decline somewhat (P=.065, nonlinearity). Exposure to less than 10 Gy was at worst, associated with only a small increased relative risk (RR) of bone cancer (RR= 0.7; 95% confidence interval = 0.2-2.2). The risk of bone cancer increased linearly (P= .04, one-tailed test) with increased cumulative dose of alkylating agents. This population-based study provides grounds for reassurance of the majority of survivors in that their risk of developing bone cancer within 20 years of 3-year survival did not exceed 0.9%. The higher risks found for bone cancer following the other specific rare types of childhood cancer provide a rational basis for surveillance. The RRs reported for bone cancer after specified levels of exposure to radiation should help in making decisions concerning future treatment protocols.

International trends in the incidence of bone cancer are not related to drinking water fluoridation

Because osteosarcomas may develop in rats exposed to fluoridated water, water fluoridation might pose a cancer risk to humans. A time trend analysis of the cumulative risk (CR) of bone cancer for the period 1958-1987 for 40 cancer registry areas showed an increased risk for young males in Canada, Europe, and the United States, and a decreased lifetime risk for either sex in Europe. This was unrelated to water fluoridation and may have resulted from changes in coding practices. Bone cancer risk was inversely related to the incidence of cancers of unknown origin, suggesting that bone metastases were erroneously coded as primary bone cancer. In 1968-1972, most areas recorded more bone cancer deaths than new cases of the disease. The mortality/incidence ratio, but not the incidence rate (IR), has dropped sharply since then, which erodes the basis of past inferences relating cancer mortality to fluoridation.

Bone cancer incidence rates in New York State: time trends and fluoridated drinking water.

Recent animal studies of the potential carcinogenicity of fluoride prompted an examination of bone cancer incidence rates. Trends in the incidence of primary bone cancers, including the incidence of osteosarcomas were examined among residents of New York State, exclusive of New York City. Average annual osteosarcoma incidence rates in fluoridated and non-fluoridated areas were also compared. Among persons less than 30 years of age at diagnosis, bone cancer incidence among males demonstrated a significant increase since 1955, while incidence among females has remained unchanged. A significant decrease in bone cancer incidence rates since 1955 was observed among both males and females age 30 years and over at time of diagnosis. Osteosarcoma incidence rates have remained essentially unchanged since 1970, among both younger and older males and females. The average annual age adjusted incidence of osteosarcomas (1976-1987) in areas served by fluoridated water supplies was not found to differ from osteosarcoma incidence rates in non-fluoridated areas. These data do not support an association between fluoride in drinking water and the occurrence of cancer of the bone.

Dose-response Relationships for Bone Cancers from Plutonium in Dogs and People

The risk of bone cancers developing from internally deposited plutonium must be estimated from studies in laboratory animals because no plutonium-induced cancers have been observed in people. Studies of the effects of 226Ra and 239Pu injected into beagle dogs at the University of Utah and 238PuO2 inhaled by beagle dogs at the Inhalation Toxicology Research Institute provide a key link to understanding the longterm effects of inhaled alpha-emitting radionuclides in people. Injected radium and plutonium are rapidly deposited in bone whereas plutonium deposited in lung by inhalation is translocated to bone more slowly, depending on its chemical form. The development of bone cancers is a late occurring effect seen after either injection of plutonium or radium or inhalation of plutonium. The incidence of bone cancers from alpha radiation to the skeletons of dogs was compared to bone cancer incidences in radium dial painters to estimate bone cancer risk from inhaled plutonium in people. A risk factor of 1200 bone cancers/106 rad to skeleton (average dose) was estimated.

Dose-response Relationships for Bone Cancers from Plutonium in Dogs and People

The risk of bone cancers developing from internally deposited plutonium must be estimated from studies in laboratory animals because no plutonium-induced cancers have been observed in people. Studies of the effects of 226Ra and 239Pu injected into beagle dogs at the University of Utah and 238PuO2 inhaled by beagle dogs at the Inhalation Toxicology Research Institute provide a key link to understanding the longterm effects of inhaled alpha-emitting radionuclides in people. Injected radium and plutonium are rapidly deposited in bone whereas plutonium deposited in lung by inhalation is translocated to bone more slowly, depending on its chemical form. The development of bone cancers is a late occurring effect seen after either injection of plutonium or radium or inhalation of plutonium. The incidence of bone cancers from alpha radiation to the skeletons of dogs was compared to bone cancer incidences in radium dial painters to estimate bone cancer risk from inhaled plutonium in people. A risk factor of 1200 bone cancers/106 rad to skeleton (average dose) was estimated.

Bone Cancer Among Female Radium Dial Workers. Latency Periods and Incidence Rates by Time After Exposure: Brief Communication 2

Bone cancer in 1,250 women exposed to radium while working in the luminous watch-dial industry between 1913 and 1929 were analyzed for times of appearance ("latency periods") and incidence rates over time after first exposure. The lowest radium intake dose associated with bone cancer, among 751 women whose intake doses had been determined, was 202.5 muCi. Mean and median bone cancer latency periods tended to decline, but average survival among women without bone cancer also decreased with increasing intake level. Bone cancer incidence rates over time were compared in 2 intake-dose groups (200--749 and greater than or equal to 759 muCi) by means of an actuarial method that takes competing risks into account. Incidence rates were consistently higher in the higher intake-dose group versus the lower dose group at each 5-year period after first exposure. The variability in the odds ratios across the time periods was not statistically significant, and the actuarial method provided little evidence for an effect of intake dose on the pattern of incidence rate over time. With the use of similar methods, no significant variability was evident in the relative odds of bone cancer over time after exposure between one group of women first exposed to radium at less than 18 years of age and another group exposed when 18 or more years old.

A Roentgenographic Study of Terminal Pathological Changes in Skeletons of Strontium-90 Treated Rats

Since strontium-induced bone lesions can be detected roentgenographically anywhere in the skeleton and in their early phases of development well before neoplastic growths become palpable or other pathological changes become gross, postmortem skeleton roentgenographs were made routinely in our laboratory in experiments on the toxic effects of strontium-90 in rats. The data on incidence of bone cancer and