Expected Cancer Deaths Research Articles

Molecular Profiling and Data Analysis of Lung Adenocarcinoma

Abstract: Lung adenocarcinoma, a major cause of cancer-related deaths globally, was examined through a comprehensive analysis of 230 resected tumors. This study integrated various sequencing techniques to profile messenger RNA, microRNA, and DNA, along with evaluating copy number variations, methylation patterns, and proteomic data. The findings revealed a notable rate of somatic mutations (average of 8.9 mutations per megabase). Among the 18 significantly mutated genes were RIT1 activating mutations and newly identified MGA loss-of-function mutations, which were mutually exclusive with MYC amplification. Gender-based differences were observed, with EGFR mutations being more common in females and RBM10 mutations in males. Genetic abnormalities in NF1, MET, ERBB2, and RIT1 were detected in 13% of cases, often in tumors lacking other activated oncogenes, suggesting their potential driver roles. Splicing alterations were driven by somatic genomic changes, as evidenced by DNA and mRNA sequencing from the same tumor, including MET mRNA exon 14 skipping in 4% of cases. While MAPK and PI(3)K pathway activity was explained by known mutations in some cases, unexplained mechanisms appeared to activate the pathways in others. These findings lay the groundwork for understanding lung adenocarcinoma’s molecular basis and offer insights for classification and further investigations. Molecular profiling is crucial for identifying actionable mutations, guiding treatment choices in advanced adenocarcinoma and acquired resistance to tyrosine kinase inhibitors. Circulating tumor DNA sequencing gains importance in NSCLC diagnostics due to its accessibility, allowing longitudinal disease monitoring. Notably, the overall cancer death rate dropped by 27% between 1991 and 2016, resulting in around 2,629,200 fewer expected cancer deaths compared to peak death rates.

PKCδ promotes the invasion and migration of colorectal cancer through c-myc/NDRG1 pathway.

Colorectal cancer (CRC) is the third cause of expected cancer deaths both in men and women in the U.S. and the third most commonly diagnosed cancer in China Targeted therapy has been proven to improve overall survival for unresectable metastatic CRC. But the location of the primary tumor or the presence of various core driver gene mutations that confer resistance may limit the utility of targeted therapy. Therefore, it is of great significance to further elucidate novel mechanisms of invasion and metastasis of CRC and find potential novel therapeutic targets. Protein Kinase C Delta (PKCδ) plays an important role in various diseases, including tumors. In CRC, the function of PKCδ on proliferation and differentiation is mostly studied but various research results were reported. Therefore, the role of PKCδ in CRC needs to be further studied, especially in tumor invasion and metastasis in CRC which few studies have looked into. The expression of PRKCD was analyzed by the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases and Immunohistochemical (IHC). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) enrichment analysis were used to explore the biological functions and pathways related to PRKCD. Lentivirus transfection was used to construct CRC cell lines with overexpression and knock-down of PKCδ or N-myc Downstream Regulated Gene 1 (NDRG1). Cell invasion and migration assay, wound healing assay were used to detect the function of PKCδ and NDRG1 in the invasion and migration of cells. Flow cytometry analysis was used to detect the influence of PKCδ on the CRC cell cycles .Immunofluorescence histochemistry ,Immunoprecipitation Assay and qPCR were used to detect the relationship of PKCδ and NDRG1. Xenograft model was used to verify the role of PKCδ in vivo. PKCδ is overexpressed in CRC and could promote Epithelial-Mesenchymal Transition (EMT) and the invasion and migration of CRC in vitro. We confirmed that PKCδ and the tumor suppressor factor NDRG1 had a co-localization relationship in CRC. PKCδ inhibited NDRG1 transcription and protein expression. Overexpressing NDRG1 could inhibit the function of PKCδ in promoting tumor invasion and migration. PKCδ could regulate c-Myc, one transcription factor of NDRG1, to down-regulate NDRG1. In vivo, overexpressing PKCδ could promote xenograft growth and volume. Thus, our results showed that PKCδ reduced the expression of NDRG1 through c-Myc, promoting the invasion and migration of CRC through promoting EMT. The increased expression of PKCδ in CRC tumor tissue could promote the invasion and migration of tumor cells, and one of the mechanisms may be regulating c-Myc to inhibit the expression of NDRG1 and promote EMT.

250Different perspectives of survival outcomes for Australian cancer patients

Abstract Background While relative survival is commonly used to describe cancer prognosis, its interpretation remains confusing. Alternative measures provide additional insights into the survival experience of Australian cancer patients. Methods Population-based cohort of over 2 million Australians diagnosed with 19 types of primary invasive cancer from 1982 to 2014 with mortality follow-up to 31 December 2015. Flexible parametric survival models were used to estimate loss of life expectancy, avoidable cancer deaths, crude survival, probability of cure and survival of uncured population for cancers diagnosed in Australia. Results There has been an overall decrease in the loss of life expectancy caused by a cancer diagnosis. Australians diagnosed in 2014 will gain an extra 432,588 life years due to the improvement in relative survival since 1982. Similarly, 29% (females) and 40% (males) of expected cancer deaths among the 2005-2014 cohort will be avoided compared to the 1985-1994 cohort. While the 10- year crude probability of cancer deaths decreased over time, patterns varied by cancer type. The crude probability of competing deaths increased with age. Between 1982 and 2009, the cure proportion increased significantly for all cancers. Conclusion Alternative measures of survival may help communicate the reducing impact that a cancer diagnosis has on average life expectancy. Key messages The growing number of Australian cancer survivors can pose emerging challenges to these patients, their caregivers, medical professionals and health-care systems in accessing or providing evidence-based survivorship and psychosocial care after a cancer diagnosis.

Estimation of Cancer Deaths in Korea for the Upcoming Years

Since the cancer has been the leading cause of deaths in Korea, estimation of the cancer deaths for the upcoming years in the population using the vital statistics is considered to be necessary. The aim of this study was to estimate the number and trends of cancer deaths in Korea. The expected numbers of cancer deaths were calculated by a time series model fitting the actual numbers of cancer deaths for each of the years 1983 through 2000 reported by Korea National Statistical Office. The options selected for the time series model included a quadratic time trend, which incorporated long-term information into the model and an autoregressive component which incorporated information about short-term fluctuations. The forecasting numbers of cancer deaths and their 95% confidence intervals were estimated for both genders and primary sites. The forecasting number of deaths from all cancers is increasing so that the cumulative number of expected cancer deaths between 2001 and 2005 would be about 309 thousand persons. Cancers of the lung, stomach, liver, and colorectum continue to be the most common causes of cancer deaths. While the numbers of expected cancer deaths in the stomach and liver show a decreasing trend, the cancer in the lung, colorectum, pancreas, breast, and oral cavity have an increasing trend. These observations indicate that cancer deaths in the near future would be increasing through the early 2000s, and there should be some urgent government's policy on the cancer management.

An updated mortality study of workers at a dye and resin manufacturing plant.

This investigation evaluated the mortality experience of workers at a dye and resin manufacturing plant in New Jersey. The retrospective follow-up study included 3266 workers employed for at least 6 months at the plant. Plant production areas were South Dyes, where anthraquinone dyes and intermediates were produced; North Dyes, where azo dyes and intermediates were produced; and plastics and additives, where various resins and additives for plastics were made. Analyses used standardized mortality ratio (SMRs) to compare the cohort's cause-specific mortality rates during 1952 to 1995 with the rates of the New Jersey population. There were fewer than expected deaths from all causes combined (728 observed vs 810 expected) and similar numbers of observed and expected cancer deaths (225 vs 232). Statistically significant work area-specific cancer excesses were limited to white men and included an excess of lung cancer in Maintenance workers (40 observed vs 26 expected; SMR, 153; 95% confidence interval [CI], 109 to 208) and in South Dyes workers (32 observed vs 19 expected; SMR, 168; CI, 115 to 237) and an excess of stomach cancer (5 observed vs 1.3 expected; SMR, 386; CI, 125 to 901), bladder cancer (4 observed vs 0.8 expected; SMR, 515; CI, 140 to 1318) and central nervous system cancer (5 observed vs 1 expected; SMR, 517; CI, 168 to 1206) in North Dyes workers. None of these increases was concentrated in work area subgroups with long duration of employment and long potential induction time. It was concluded that the excess of bladder cancer probably was due to exposure to carcinogenic arylamines at another facility, where some employees had worked before coming to the study plant. The other cancer increases may be attributable to chance, to uncontrolled confounding by smoking, or to an unidentified occupational exposure.

Mortality study of ethanol and isopropanol production workers at two facilities.

The mortality experience of alcohol process workers (N = 1031) from two chemical plants was followed from the early 1940s to 1983. Reported associations of the production of ethanol and isopropanol by the strong-acid process with upper respiratory tract cancers, heart disease, and lympho- and reticulosarcoma were tested with both external and internal comparisons. Excesses of cancers of the larynx, buccal cavity, and pharynx, based on very small numbers, were observed. There was one death due to sinus cancer. It could not be concluded that there were work-related effects on mortality due to heart disease or lympho- or reticulosarcoma. Workers assigned to the production of isopropanol by the weak-acid method showed no evidence of excess cancer mortality (0 observed, 1.9 expected cancer deaths). The absence of major risks among strong-acid workers can be explained by the initiation of engineering controls and health monitoring that took place after the original medical observations.

A follow-up study of workers at a dye and resin manufacturing plant.

A total of 2642 men employed at a dye and resin manufacturing plant in New Jersey were observed from the opening of the plant in 1952 through 1985, and their mortality rates were compared with the rates of United States white men. The workers' mortality experience was related to former employment at the Cincinnati Chemical Works, which had produced or used benzidine and beta-naphthylamine. The 2553 men who had never worked at the Cincinnati Chemical Works had fewer than expected deaths from all causes combined (317 observed/402 expected) and equal numbers of observed and expected cancer deaths (89/89). The 89 former Cincinnati Chemical Works employees had an excess of cancer (17/8.6, P = .02), which was due to increased mortality from bladder (3/0.25, P = .004), kidney (2/0.21, P = .04), and CNS (2/0.22, P = .04) cancer. There also were several increases in cancers among men employed in certain work areas at the New Jersey plant. These included elevated mortality from lung (18/9.2, P = .01) and liver (3/0.46, P = .02) cancer among maintenance workers, from stomach (3/0.40, P = .02) and CNS (3/0.44, P = .02) cancer among azo dye workers, and from lung cancer (4/0.91, P = .03) among epichlorohydrin workers. The lung cancer excess among maintenance workers increased with length of employment, suggesting an association with an unidentified occupational exposure. Other associations were based on small numbers of deaths, and their interpretation is not clear.

Carcinogenicity of radiation doses caused by the Chernobyl fall-out in Sweden, and prevention of possible tumors.

The fallout from the Chernobyl reactor resulted in radioactive fall-out in eastern Sweden leading to a ground radiation intensity of between 2 and 500 microR h-1 above the 10-15 microR h-1 background, an average external cumulative dose of about 3-4 mSv (0.3-0.4 rem) to about 1 million people, or about 3500 man-Sv (350,000 man-rem) over 50 years, or 70 man-Sv per year with a maximum dose to a few individuals of 40 mSv. The corresponding figures reported for civilians around Chernobyl is 8.6 million man-rem in 1986 and 29 million man-rem over 50 years, or 600,000 man-rem (equivalent to about 6000 man-Sv) per year. If Swedish doses are averaged over the whole population, the average is about 1 mSv or 10,000 man-Sv, or 200 man-Sv per year. The thyroid uptake of 131I is approximately 0.1-0.2 kBq (0.005 microCi) and the total body uptake of 137Cs, 1 kBq (0.03 microCi), resulting in an approximate internal dose of 0.02 mSv. If a linear dose-response curve is assumed, an increase of the normal cancer mortality incidence in the million Swedes affected by 3500 man-Sv per 50 years from 200,000 to about 200,070 can be assumed. Corresponding figures for all of Sweden are 8,000,000 inhabitants, 7000 man-Sv, 1,720,000 normal cancer deaths, and 1,720,140 expected cancer deaths. Corresponding figures reported for the population outside the 30 km evacuation zone around Chernobyl are 300,000 man-Sv, and an increase from 6,800,000 cancer deaths per 50 years to 6,806,000 cancer deaths.

Respiratory organs cancer mortality in New Jersey counties and the relationship with selected demographic and environmental variables

The state of New Jersey (N.J.) has been thought to have an unusually high overall cancer mortality rate; this assumption has been based on national 1950–1969 mortality data for N.J. counties. This study presents an analysis of more recent rates of respiratory cancer mortality in 21 N.J. counties during 1968–1977, a comparison with the 1950–1969 rates, and associations between current respiratory cancer mortality rates and selected demographic and environmental variables. Age-adjusted mortality rates for cancer of respiratory organs were calculated for the N.J. counties during the period 1968–1977 and compared with the period 1950–1969, with the Surveillance, Epidemiology, and End Results (SEER) survey, and with cancer mortality in the United States, 1973–1977. The county rates were also correlated with chemical toxic-waste disposal sites (CTWDS), annual per capita income, percentage of the population employed in chemical industries, the density of population, and the urbanization index of each of 21 N.J. counties. The lung, bronchus, trachea, and pleura cancer mortality rates among white and nonwhite males and females in N.J. were substantially higher than the national rates during the period 1950–1969. In more recent years, the increases in U.S. mortality rates for lung, bronchus, trachea, and pleura cancers were significantly greater ( P < 0.01) than those found in most of the 21 N.J. counties. As a consequence, the national rates are now more comparable to N.J. rates. Although the gaps between N.J. and the United States in these rates have narrowed, the observed number of laryngeal and lung cancer deaths remained significantly higher ( P < 0.01 to P < 0.0001) than expected cancer deaths, based on U.S. rates, among one or more subgroup populations (white and nonwhite males and females) in several N.J. counties. Among white men in Middlesex, Camden, Burlington, and Ocean counties, the observed number of deaths for lung cancer was found to be significantly ( P < 0.0001) greater than the expected number of deaths. In Hudson county observed deaths from both laryngeal and lung cancer among white men were significantly greater than the expected number of deaths from these cancers ( P < 0.0001). Statistically significant and positive correlations were found between laryngeal cancer mortality and CTWDS, urbanization index, and population density. Lung cancer mortality also correlated significantly with CTWDS in N.J. Both larynx and lung cancer mortality showed significant and consistent negative correlations with annual per capita-income in N.J. Some of the implications of the study findings are discussed and recommendations made for future investigations.

Gastrointestinal cancer mortality in New Jersey counties, and the relationship with environmental variables.

The State of New Jersey (NJ) USA has been thought to have an unusually high cancer mortality rate; this assumption has been based on 1950-1969 mortality data for its 21 counties. This paper presents an analysis of gastrointestinal (GI) cancer mortality rates in New Jersey counties during 1968-1977, a comparison with the 1950-1969 rates, and associations between current GI cancer mortality rates and selected environmental variables. Age-adjusted mortality rates for GI cancers were calculated for the 21 NJ counties during the period 1968-1977, and were compared with the period 1950-1969, with the Surveillance, Epidemiology and End Results (SEER) survey and with cancer mortality in the US, 1973-1977. The county rates were also correlated with: the distribution of chemical toxic waste disposal sites; annual per capita income; the rates of low birth weight, birth defects, and infant mortality; chemical industry distribution; percentage of the population employed in chemical industries; the density of population; and the urbanization index for each of the counties. Some of the major findings are: Age-adjusted GI cancer mortality rates (all sites combined) were higher than national rates in 20 of 21 NJ counties. In comparison with national trends, NJ stomach cancer rates have declined less, oesophageal cancer rates have declined more, and pancreatic cancer mortality rates have followed similar patterns. Cancer mortality rates in NJ during the period 1968-1977 significantly (p less than 0.0001) exceeded national rates for cancer of the oesophagus (white male, non-white male), stomach (men and women), colon (white male, white female, non-white female), and rectum (whites only). In 18 of the 21 NJ counties, the observed number of cancer deaths for at least one GI cancer site was significantly greater than expected at the 0.0001 level for at least one population subgroup. Among white men, a significant (p less than 0.0001) excess of observed over expected cancer deaths was observed for three or more GI cancer sites in seven counties. The environmental variables that were most frequently associated with GI cancer mortality rates (except pancreatic cancer) were degree of urbanization, population density, and chemical toxic waste disposal sites. Some of the implications of the study findings are discussed and recommendations made for future investigations.

Characteristics of cancer in the Eskimos of Southwestern Alaska.

Using records from the Public Health Service Alaska Native Hospital at Bethel, Alaska, the author reviews all known cancers occurring among the Yupik Eskimos of Southwestern Alaska during the 101/2 year period from July 1957 through December 1967. Since this facility is the source, direct or indirect, of virtually all medical care provided to a well-defined population, these records can be used for a reasonably accurate estimate of incidence, mortality, and other epidemiologic characteristics of cancer in this group. The 85 tumors in the series give a crude incidence of 82.4/100,000 for males and 106.3/100,000 for females. Forty-six per cent of the total number originated in the alimentary tract. In both sexes, the commonest cancer site was the esophagus. Another common site in both sexes was the kidney, as was the thyroid in females. There were 45 deaths from cancer, including one person with two separate advanced malignancies. Standardized mortality ratios for cancer were calculated for the Eskimos and other populations based on the U.S. Caucasian death rates for 1962. Those for Yupik Eskimo males and females were 73 and 79, respectively (U. S. Caucasian = 100), for histologically proven cases and 84 and 94, respectively, for all diagnosed cases. A comparison of observed with expected cancer deaths (based on U.S. Caucasian rates for 1962–63) revealed a great excess of esophageal cancer in the Eskimos of both sexes. Further study of this problem, with particular reference to possible causative factors in traditional Eskimo cultural practices, seems warranted. Despite widespread opinion to the contrary, cancer is a relatively common disease in Eskimos and an increasingly serious and expensive health problem in the north.