Histopathological and molecular prognostic markers in medulloblastoma： c-myc, N-myc, TrkC, and anaplasia

Several molecular and histopathologieal prognostic markers have been proposed for the therapeutic stratification of meduUoblastoma patients. Amplification of the c-mye oneogene, elevated levels of c-mye mRNA, or tumor anaplasia have been associated with worse clinical outcomes. In contrast, high TrkC mRNA expression generally presages longer survival. The goal of this study was to evaluate the     

Trends in incidence,mortality, and survival for kidney cancer in Canada, 1986–2007

Purpose

Kidney cancer is one of the fastest rising cancers worldwide. We aimed to examine the trends in incidence, mortality, and survival for this cancer in Canada.

Methods

Incidence data for kidney cancer for 1986–2010 were from the Canadian Cancer Registry and the National Cancer Incidence Reporting System. These data were only available up to 2007 for the province of Quebec and consequently for the same year nationally, for Canada. Mortality data for 1986–2009 were from the Canadian Vital Statistics Death Database. Changes in age-standardized rates were analyzed by Joinpoint regression. Incidence rates were projected to 2025 using a Nordpred age-period-cohort model. Five-year relative survival ratios (RSR) were analyzed for 2004–2008 and earlier periods.

Results

Between 1986 and 2007, the age-standardized incidence rate (ASIR) per 100,000 rose from 13.4 to 17.9 in males and 7.7 to 10.3 in females. Annual increases in ASIR were greatest for age groups <65 years (males) and ≥65 years (females). The ASIRs increased significantly over time in both sexes for renal cell carcinoma (RCC) but not for other kidney cancer types. RCC rates are projected to increase until at least 2025. Mortality rates decreased only slightly in each sex since 1986 (0.4 %/year in males; 0.8 %/year in females). The 5-year RSR for kidney cancer was 68 % but differed largely by morphology and age, and has increased slightly over time.

Conclusions

The incidence rate of kidney cancer in Canada has risen since at least 1986, led largely by RCC. Increasing detection of incidental tumors, and growing obesity and hypertension rates are possible factors associated with this increase. Greater prevention of modifiable risk factors for kidney cancer is needed.     

Incidence,survival, and mortality of cancer in children and young adolescents in Belgium and the Netherlands in 2004–2015: A comparative population-based study

International comparisons of cancer surveillance measures may provide insight into inequalities in registration practices, etiological factors, and treatment strategies. This study aimed to compare incidence, survival, and mortality of cancer in children and young adolescents between Belgium and the Netherlands. All children (0–14 years) and young adolescents (15–17 years) diagnosed with cancer between 2004 and 2015 were selected from the population-based cancer registries of Belgium (N = 4739) and the Netherlands (N = 7322). Differences in incidence and mortality were expressed as standardized rate ratios (SRR; BE/NL). Five-year observed survival was calculated using the Kaplan–Meier method. During 2004–2015, the overall cancer incidence among children and young adolescents was similar in both countries. Incidence of neuroblastoma was significantly higher in Belgian children (2010–2015: SRR = 1.3, 95% CI 1.0–1.6). Five-year survival of all malignant cancers was comparable in 2010–2015, exceeding 80% in both age groups. Remarkable differences in survival existed in children for malignant central nervous system (CNS) tumors in 2004–2009 (BE = 62%, NL = 45%), for acute myeloid leukemia (BE = 68%, NL = 78%) and rhabdomyosarcomas (BE = 60%, NL = 79%) in 2010–2015, and for neuroblastoma in both periods (2004–2009: BE = 76%, NL = 64%; 2010–2015: BE = 82%, NL = 64%). Overall cancer mortality in children decreased by approximately 3 percent-points annually in both countries, but was slightly lower in Belgium in 2004–2009 (SRR = 0.9, 95% CI 0.7–1.0). Despite differences for specific cancer types, overall cancer incidence, survival, and mortality were comparable between Dutch and Belgian children and young adolescents in 2010–2015. Variability in screening, diagnosis, and registration practices probably explains the observed differences in incidence and survival of neuroblastoma and malignant CNS tumors.     

Transforming growth factor-β1 in carcinogenesis,progression, and therapy in cervical cancer

Transforming growth factor β1 (TGF-β1) is a multifunctional cytokine that plays important roles in cervical tumor formation, invasion, progression, and metastasis. TGF-β1 functions as a tumor inhibitor in precancerous lesions and early stage cancers of cervix whereas as a tumor promoter in later stage. This switch from a tumor inhibitor to a tumor promoter might be due to various alterations in TGF-β signaling pathway, such as mutations or loss of expression of TGF-β receptors and SMAD proteins. Additionally, the oncoproteins of human papillomaviruses have been shown to stimulate TGF-β1 expression, which in turn suppresses host immune surveillance. Thus, in addition to driving tumor cell migration and metastasis, TGF-β1 is believed to play a key role in promoting human papillomavirus infection by weakening host immune defense. In this article, we will discuss the role of TGF-β1 in the expression, carcinogenesis, progression, and therapy in cervical cancers. A better understanding of this cytokine in cervical carcinogenesis is essential for critical evaluation of this cytokine as a potential prognostic marker and therapeutic target.     

Trends for in situ and Invasive Melanoma in Queensland, Australia, 1982–2002

Objectives Queensland, the north-eastern state of Australia, has the highest incidence of melanoma in the world. Control measures started earlier here than probably anywhere else in the world; early detection programmes started in the 1960s and primary prevention in the 1980s. Data from the population-based Queensland Cancer Registry therefore provide an internationally unique data source with which to assess trends for in situ and invasive melanomas and to consider the implications for early detection and primary prevention. Methods We used Poisson regression to estimate the annual percentage change in rates across 21 years of incidence data for in situ and invasive lesions, stratified by age and sex. Joinpoint analyses were used to assess whether there had been a statistically significant change in the trends. Results In situ melanomas increased by 10.4% (95% CI: 10.1%, 11.1%) per year among males and 8.4% (7.9%, 8.9%) per year among females. The incidence of invasive lesions also increased, but not as quickly; males 2.6% (2.4%, 2.8%), females 1.2% (0.9%, 1.5%). Valid data on thickness was only available for 1991 to 2002 and for this period thin-invasive lesions were increasing faster than thick-invasive lesions (for example, among males: thin 3.8%, thick 2.0%). We found some suggestive evidence of lower proportionate increase for the most recent years for both in-situ and invasive lesions, but this did not achieve statistical significance. Among people younger than 35 years, the incidence of invasive melanoma was stable and there was a suggestion of a birth cohort effect from about 1958. Mortality rates were stable across all ages, and there was a suggestion of decreasing rates among young women, although this did not achieve statistical significance. Conclusion Age-standardised incidence is continuing to increase and this, in combination with a shift to proportionately more in situ lesions, suggests that the stabilisation of mortality rates is due, in large part, to earlier detection. For primary prevention, after a substantial period of sustained effort in Queensland, there is some suggestive, but not definitive, evidence that progress is being made. Incidence rates are stabilising in those younger than 35 years and the proportionate increase for both in situ and invasive lesions appears to be lower for the most recent period compared with previous periods. However, even taking the most favourable view of these trends, primary prevention is unlikely to lead to decreases in the overall incidence rate of melanoma for at least another 20 years. Consequently, the challenge for primary prevention programmes will be to maintain momentum over the long term. If this can be achieved, the eventual public-health benefits are likely to be substantial.     

Citizenship,length of stay,and screening for breast,cervical, and colorectal cancer in women, 2000–2010

Background

Two factors jointly account for significant gaps in access to health care among immigrants who are present in the U.S.—legal status, and length of residence. The objective of this study is to examine the association between citizenship and length of residence in the U.S. and cancer screening (breast, cervical, and colorectal) among women.

Methods

We analyzed 11 years (2000–2010) of consolidated data from the Medical Expenditure Panel Survey linked with the National Health Interview Survey. Multivariate analyses compared cancer screening among U.S.-born citizens (n?=?58,484), immigrant citizens (n?=?8,404), and immigrant non-citizens (n?=?6,564).

Results

Immigrant non-citizens living in the U.S. for less than 5 years were less likely to receive guideline-concordant breast (OR?=?0.68 [0.53–0.88]), cervical (OR?=?0.65 [0.54–0.78]), and colorectal (OR?=?0.31 [0.19–0.50]) cancer screening compared to U.S.-born citizens. Immigrant citizens and non-citizens living in the U.S. for 5 years or more had higher odds of being screened for breast and cervical cancer compared to U.S.-born citizens; (OR?=?1.26 [1.13–1.41] and OR?=?1.17 [1.06–1.29]) for immigrant citizens, (OR?=?1.28 [1.13–1.45] and OR?=?1.23 [1.09–1.38]) for non-citizens. Immigrant non-citizens living in the U.S. for 5 years or more had lower odds of being screened for colorectal cancer compared to U.S.-born citizens (OR?=?0.76 [0.65–0.90]).

Conclusions

Based on these findings, duration mandates in immigration policy may indirectly influence future pathways to preventive health care and cancer disparities disproportionately affecting immigrant women. We suggest that limits of duration mandates be reevaluated, as they may offer pathways to preventive health care for this vulnerable population, and prevent future cancer disparities.

     

MicroRNAs,TGF-β signaling,and the inflammatory microenvironment in cancer

Inflammatory cells and mediators form a major part of the tumor microenvironment and play important roles in the regulation of cancer initiation, tumor cell proliferation, and metastasis. MicroRNAs (miRNAs) play important roles in several physiological and pathological processes, including the regulation of the inflammatory microenvironment in cancer. Transforming growth factor-β (TGF-β) is an inflammation-related cytokine that functions in both tumor suppression and promotion; however, its underlying molecular mechanisms remain unclear. Recent evidence indicates an association between miRNAs and TGF-β signaling, providing new insight into the nature of the inflammatory microenvironment in cancer. The present review is an overview of the interaction between miRNAs and inflammatory cytokines, with emphasis on the cross talk between TGF-β signaling and miRNAs and their influence on cancer cell behavior. The emerging roles of miRNAs in cancer-related inflammation and the potential to target miRNA signaling pathways for cancer therapy are also discussed.     

Histochemical and Immunohistochemical Study of α-SMA,Collagen, and PCNA in Epithelial Ovarian Neoplasm

Background: Alpha-smooth muscle actin (α-SMA) is an isoform of actin, positive in myofibroblasts and is an epithelial to mesenchymal transition (EMT) marker. EMT is a process by which tumor cells develop to be more hostile and able to metastasize. Progression of tumor cells is always followed by cell composition and extracellular matrix component alteration. Increased α-SMA expression and collagen alteration may predict the progressivity of ovarian neoplasms. Objective: The aim of this research was to analyse the characteristic of α-SMA and collagen in tumor cells and stroma of ovarian neoplasms. In this study, PCNA (proliferating cell nuclear antigen) expression was also investigated. Methods: Thirty samples were collected including serous, mucinous, endometrioid, and clear cell subtypes. The expression of α-SMA and PCNA were calculated in cells and stroma of ovarian tumors. Collagen was detected using Sirius Red staining and presented as area fraction. Results: The overexpressions of α-SMA in tumor cells were only detected in serous and clear cell ovarian carcinoma. The histoscore of α-SMA was higher in malignant than in benign or borderline ovarian epithelial neoplasms (105.3±129.9 vs. 17.3±17.1, P=0.011; mean±SD). Oppositely, stromal α-SMA and collagen area fractions were higher in benign than in malignant tumors (27.2±6.6 vs 20.5±8.4, P=0.028; 31.0±5.6 vs. 23.7±6.4, P=0.04). The percentages of epithelial and stromal PCNA expressions were not significantly different between benign and malignant tumors. Conclusion: Tumor cells of serous and clear cell ovarian carcinoma exhibit mesenchymal characteristic as shown by α-SMA positive expression. This expression might indicate that these subtypes were more aggressive. This research showed that collagen and α-SMA area fractions in stroma were higher in benign than in malignant neoplasms.     

Shrinking, widening, reversing, and stagnating trends in US socioeconomic inequities in cancer mortality for the total, black, and white populations: 1960–2006

Objectives of study  

To test recent claims that cancer inequities are bound to increase as population health improves.     

Dietary β-carotene,cigarette smoking,and lung cancer in men

A cohort of 5,080 men living in a retirement community in California (United States) and initially free from lung cancer were followed from June 1981 to December 1989. At recruitment, each study participant completed a mailed questionnaire which requested information on the subject's medical history, use of cigarettes, and usual consumption frequencies during the preceding 12 months of 44 vegetable and fruit items. Men who had never smoked had the highest mean daily intake of -carotene (8,505 g), followed by past smokers (7,761 g) and then by current smokers (6,178 g). -Carotene intake of the subject's wife was correlated significantly with that of the husband in the 4,018 spouse pairs (r=0.46; P=0.0001). Among men with similar smoking habits, dietary -carotene intake significantly decreased with the spouse's smoking habit: never, past, and current smokers (P=0.004; test for linear trend). During 31,477 person-years of follow-up, 125 incident cases of lung cancer were observed among the cohort of 5,080 men. Age-adjusted relative risks for lung cancer were below unity (i.e., demonstrating a reduced risk) for higher relative to lower consumption of -carotene, of all vegetables and fruits, and of yellow vegetables alone. However, these relative risks approached or crossed the null value when adjusted for personal smoking.This study was supported by US Public Health Service grants CA-17054 and CA-32197 from the National Cancer Institute.     

Vitamin D,calcium, and retinol intake,and pancreatic cancer in a population-based case–control study in the San Francisco Bay area

Objective  

The aim of this study was to evaluate a complex association among intake of dietary vitamin D, calcium, and retinol, and pancreatic cancer risk.     

Trends in adult leukemia incidence and survival in Denmark, 1943–2003

The etiology of leukemia is largely unknown. Ecological data indicating trends in incidence and survival can provide information about changes in risk factors, can reflect underlying changes in diagnostic classification, and can measure therapeutic advances. From the records of the Danish Cancer Registry with registration starting from 1943, we calculated age-specific, period-specific, and age-standardized (world standard) incidence rates of chronic lymphoid leukemia (CLL), acute lymphoid leukemia (ALL), chronic myeloid leukemia (CML), and acute myeloid leukemia (AML) for persons above the age of 18. Kaplan–Meier survival curves and median survival times were calculated. Between 1943 and 2003, there were 26,036 cases of leukemia reported. The age-specific incidence rates of CLL, CML, and AML were higher for older men and women, while the incidence rates of ALL by age were more homogeneous. The age-standardized incidence rates during the study period increased for CLL and AML, increased less strongly for ALL, and decreased for CML in both men and women, although the incidence rates for women were almost always lower. Patients with CLL had the longest survival time in all age groups. The median survival time increased for all leukemia subtypes throughout the period of study most pronounced for CLL since 1950 and CML since 1990.     

Age–incidence patterns of primary CNS tumors in children,adolescents, and adults in England

Around 25% of all tumors in those 0–14 years of age and 9% in those 15–24 years of age involve the CNS. They are the most common cause of cancer-related deaths in both age groups. In adults 25–84 years of age, the proportion of CNS tumors is 2%; 5-year overall survival is 10%–15%; and survivors have considerable morbidity. Comprehensive up-to-date population-based incidence data on these tumors are lacking. We present incidence rates for primary CNS tumors based on data derived from the high-quality national cancer registration system in England. A total of 54,336 CNS tumors of malignant, benign, and uncertain behavior were registered across the whole of England from 1995 through 2003. The age-standardized rates for all ages (0–84 years) was 9.21 per 100,000 person-years. This is higher than previously reported for England because it includes nonmalignant CNS tumors and hence gives a more accurate picture of burden of disease. The age-standardized rates for those 0–14 years of age, 15–24 years of age, and 25–84 years of age were 3.56, 3.26, and 14.57 per 100,000 person-years, respectively. In this article, we describe the changing patterns in the epidemiology of primary CNS tumors in these three age groups with respect to sex, tumor behavior, and histology using the current WHO classification. This information will provide a reference for future studies nationally and internationally and make comparisons relevant and meaningful.     

Prospective study of serum retinol, β-carotene, β-cryptoxanthin, and lutein/zeaxanthin and esophageal and gastric cancers in China

Objective: This study examined the relationship between pretrial serum concentrations of retinol, -carotene, -cryptoxanthin, and lutein/zeaxanthin and the subsequent risk of developing esophageal squamous cell carcinoma and gastric cardia or non-cardia adenocarcinoma in subjects selected from a randomized nutritional intervention trial in Linxian, China, a region with epidemic rates of esophageal and gastric cardia cancer. Methods: We used a stratified case–cohort design to select cohort members for inclusion in this study. In all we measured serum concentrations of the above vitamins in 590 esophageal, 395 gastric cardia, and 87 gastric non-cardia case subjects as well as in 1053 control subjects. Relative risks (RRs) were estimated using Cox proportional hazards models. Results: Median values in our cohort were low for serum retinol (33.6 g/dl), -carotene (4.3 g/dl), and -cryptoxanthin (3.5 g/dl) , but were high for lutein/zeaxanthin (40.0 g/dl). Gastric cardia cancer incidence fell 10% for each quartile increase in serum retinol (RR = 0.90, 95% CI = 0.83–0.99). For esophageal cancer, an inverse association with retinol levels was found only in male non-smokers (RR = 0.79 per quartile increase, 95% CI = 0.63–0.99). For gastric non-cardia cancer, an inverse association was limited to subjects 50 years old or younger (RR = 0.58 per quartile, 95% CI = 0.31–0.96). For -cryptoxanthin there was a borderline significant protective association for gastric non-cardia cancer (RR = 0.88 per quartile, 95% CI = 0.76–1.0). In contrast, we found the incidence of gastric non-cardia cancer increased (RR = 1.2 per quartile, 95% CI = 1.0–1.3) with increasing concentration of serum lutein/zeaxanthin. Conclusions: In this population, we found that low retinol and high lutein/zeaxanthin concentrations increased the risks of gastric cardia and gastric non-cardia cancer respectively. We found that there were no strong associations between any of the other analytes and any of the cancer sites.     

Population-based Survival from Cancers of Breast,Cervix and Ovary in Women in Mumbai,India

Background: Breast, cervix and ovarian cancers contribute more than 45% of the total in women in Mumbai ‍and survival proportions for these neoplasms are very high in most developed populations in the World. The authors ‍here report and discuss the population-based survival for these cancers in Mumbai, India. ‍Methods: Follow-up information on 4865 cancers of breast, cervix and ovary, registered in the Mumbai Population ‍Based Cancer Registry for the period 1992-1994 was obtained by a variety of methods, including matching with ‍death certificates from the Mumbai vital statistics registration system, postal/telephone enquiries, home visits and ‍scrutiny of medical records. The survival for each case was determined as the duration between the date of diagnosis ‍and date of death, date of loss to follow-up or the closing date of the study (December 31st, 1999). Cumulative ‍observed and relative survival was calculated by the Hakulinen Method. For comparison of results with other ‍populations, age-standardized relative survival (ASRS) was calculated by directly standardizing age specific relative ‍survival to the specific age distributions of the estimated global incidence of major cancers in 1985. The log rank test ‍was used in univariate analysis to identify the potentially important prognostic variables. The variables showing ‍statistical significance in univariate analysis were introduced stepwise into a Cox Regression model to identify the ‍independent predictors of survival. ‍Results: The 5-year relative survival rates were 46.2% for breast, 47.7% for the cervix and 25.4% for the ovary. ‍Higher survival was observed for those younger than 35 years for all these three sites. For each, survival declined ‍with advancing age. Single patients who remained unmarried had better survival. For all sites Muslims had a better ‍and Christians a lower survival as compared to Hindus. Education did not appear to be of significance. Survival ‍decreased rapidly with advancing clinical extent of disease for all sites. With localized cancer, 5-year rates ranged ‍from 54.7% to 69.3%, for regional spread 20.4% to 41.6% and distant metastasis not a single site recorded more ‍than 5%. On multivariate analysis, age and extent of disease emerged as independent predictors of survival for all ‍the sites. ‍Conclusion: All the sites included in the study demonstrated moderate survival rates with significant variation. ‍Comparison with other populations revealed lower survival rates as compared to developed countries, particularly ‍for breast and ovary. In Indian populations survival proportions did not show much variation for these cancers. ‍Early detection and treatment are clearly important factors to reduce the mortality from these cancers. ‍