Improving the reporting of cancer-specific mortality and survival in research using cancer registry data

Population-based registries are increasingly used in cancer research. In such studies, cancer-specific mortality or survival is frequently used as the primary outcome. To determine whether a putative cancer was part of the causal chain of events leading to death, cancer registries primarily rely on death certificates. Hence, they depend on the subjective interpretation of information available to medical examiners at the time of death. Misclassification may occur: studies report misclassification of cancer as a cause of death in 15%–35% of death certificates based on evaluation by expert panels and/or autopsy reports. Further misclassification may occur when coding death causes in the cancer registry. Researchers should be aware of potential misclassification bias when using cancer registry data. Differential misclassification may bias the results towards or away from the null hypothesis, depending on whether there is relative over- or under-reporting of cancer-related deaths in one group. Strategies to improve reporting of cancer-specific survival/mortality include (1) describing the procedure used to identify cancer-specific deaths; (2) considering the use of multiple definitions of cancer-related deaths (strict/liberal definitions of cancer-specific deaths, and/or addition of relative survival as an outcome); and (3) reporting cancer-specific survival/mortality together with the objectively measured parameters overall survival or all-cause mortality.     

Increased incidence of rare cancers and varied age distributions by cancer group: A population-based cancer registry study in Hiroshima Prefecture,Japan

BackgroundEpidemiological characteristics of many types of rare cancers are limited especially in Asia. Therefore, this study aimed to describe the burden and changing time trends of rare cancers in Hiroshima, Japan.MethodsThe internationally agreed RARECAREnet list of rare cancers was used to identify patients diagnosed with cancers from 2005 to 2015 who were registered in the Hiroshima Prefecture Cancer Registry. Quality indicators specific to rare cancers were assessed by cancer grouping. Crude incidence rates (IRs) and age-standardized rates (ASRs) were calculated for 216 single cancers (rare and common) included in the list. A joinpoint regression was used to analyze age distribution and time trends in the ASRs for 12 internationally agreed rare cancer families. Quality indicators, ASRs, and IRs in Japan were identified to examine IR differences and the effects on data accuracy.ResultsThe 231,328 cases were used to calculate the IRs of each cancer. Epithelial tumors in rare families increased with age, but nonepithelial tumors occurred at any age. The proportion of rare cancer families to total cancers was stable. The time trend for families of head and neck cancers (annual percent change and 95 % confidence interval: 2.4 %; 1.2–3.7 %), neuroendocrine tumors (6.6 %; 5.1–8.1 %), and hematological cancers (4.3 %; 3.2–5.5 %) markedly increased.ConclusionThe ASRs of several rare cancers increased because of increased knowledge of these diseases, improved diagnostic techniques, and aggressive diagnoses.     

Impact of variation in cancer registration practice on observed international cancer survival differences between International Cancer Benchmarking Partnership (ICBP) jurisdictions

BackgroundInternational cancer survival comparisons use cancer registration data to report cancer survival, which informs the development of cancer policy and practice. Studies like the International Cancer Benchmarking Partnership (ICBP) have a duty to understand how registration differences impact on survival prior to drawing conclusions.MethodsKey informants reported differences in registration practice for capturing incidence date, death certificate case handling and registration of multiple primary tumours. Sensitivity analyses estimated their impact on one-year survival using baseline and supplementary cancer registration data from England and Sweden.ResultsVariations in registration practice accounted for up to a 7.3 percentage point difference between unadjusted (estimates from previous ICBP survival data) and adjusted (estimates recalculated accounting for registration differences) one-year survival, depending on tumour site and jurisdiction.One-year survival estimates for four jurisdictions were affected by adjustment: New South Wales, Norway, Ontario, Sweden. Sweden and Ontario’s survival reduced after adjustment, yet they remained the jurisdictions with the highest survival for breast and ovarian cancer respectively. Sweden had the highest unadjusted lung cancer survival of 43.6% which was adjusted to 39.0% leaving Victoria and Manitoba with the highest estimate at 42.7%. For colorectal cancer, Victoria’s highest survival of 85.1% remained unchanged after adjustment.ConclusionPopulation-based cancer survival comparisons can be subject to registration biases that may impact the reported ‘survival gap’ between populations. Efforts should be made to apply consistent registration practices internationally. In the meantime, survival comparison studies should provide acknowledgement of or adjustment for the registration biases that may affect their conclusions.     

Occupational disparities in survival from common cancers in Japan: Analysis of Kanagawa cancer registry

BackgroundLittle is known about occupational disparities in survival for common cancer sites in Japan.MethodsUsing data from a population-based cancer registry, we identified 32,870 cancer patients diagnosed during 1992–2011. We followed the patients for 5 years (median follow-up time 5.0 years). For each individual, we classified their longest-held occupation into 5 classes (upper non-manual, lower non-manual, manual, farmer, and others) following the Erikson-Goldthorpe-Portocarero scheme. Poisson regression models were used to estimate overall and site-specific mortality rate ratios (MRRs) and 95% confidence intervals (CI) for each occupational class, adjusted for sex, age, and diagnosis year. Upper non-manual workers served as the reference group. Additionally, using a binary categorization of occupations (manual workers versus non-manual workers), a causal mediation analysis with 4-way decomposition was performed to investigate the potential mediation of the association between occupation and overall mortality by cancer stage.ResultsOverall prognosis was good in this population (5-year overall survival was 81.7%). Compared with upper non-manual workers, both overall and cancer-specific mortality was higher in lower non-manual workers (MRR=1.14, 95% CI 1.05–1.24) and manual workers (MRR=1.40, 95% CI 1.29–1.53). After adjusting for the mediating influence of prognostic factors (stage and treatment), the observed occupational differences were attenuated but remained significant in manual workers: MRR = 1.23 (95% CI 1.08–1.39). Observed occupational disparities tended to be attributable to common cancers, i.e., stomach and lung among men and female breast cancer. Additionally, manual workers had 1.25 times higher odds for advanced stage. In the mediation analysis, the overall proportion explained by mediating effect of cancer stage was 29% (4% due to mediated interaction and 25% due to pure indirect effect).ConclusionWe documented occupational disparities in survival from commonly-occurring cancers in Japan. Occupational differences in cancer stage may explain one-third of the survival disparities.     

Probabilities of dying from cancer and other causes in French cancer patients based on an unbiased estimator of net survival: A study of five common cancers

BackgroundNet survival is the survival that would be observed if cancer were the only possible cause of death. Although it is an important epidemiological tool allowing temporal or geographical comparisons, it cannot inform on the “crude” probability of death of cancer patients; i.e., when taking into account other possible causes of deaths.MethodsIn this work, we provide estimates of the crude probabilities of death from cancer and from other causes as well as the probability of being alive up to ten years after cancer diagnosis according to the age and year of diagnosis. Based on a flexible excess hazard model providing unbiased estimates of net survival, our methodology avoids the pitfalls associated with the use of the cause of death. We used data from FRANCIM, the French network of cancer registries, and studied five common cancer sites: head and neck, breast, prostate, lung, and colorectal cancers.ResultsFor breast, prostate, and colorectal cancers, the impact of the other causes on the total probability of death increased with the age at diagnosis whereas it remained negligible for lung and head and neck cancers whatever the age. For breast, prostate, and colorectal cancer, the more recently was the cancer diagnosed, the less was the probability of death from cancer.ConclusionThe crude probability of death is an intuitive concept that may prove particularly useful in choosing an appropriate treatment, or refining the indication of a screening strategy by allowing the clinician to estimate the proportion of cancer patients who will die specifically from cancer.     

The validity of cancer information on death certificates in Norway and the impact of death certificate initiated cases on cancer incidence and survival

BackgroundDeath certificates are an important source of information for cancer registries. The aim of this study was to validate the cancer information on death certificates, and to investigate the effect of including death certificate initiated (DCI) cases in the Cancer Registry of Norway when estimating cancer incidence and survival.MethodsAll deaths in Norway in the period 2011–2015 with cancer mentioned on the death certificates were linked to the cancer registry. Notifications not registered from other sources were labelled death certificate notifications (DCNs), and considered as either cancer or not, based on available information in the registry or from trace-back to another source.ResultsFrom the total of 65 091 cancers mentioned on death certificates in the period 2011–2015, 58,425 (89.8%) were already in the registry. Of the remaining 6 666 notifications, 2 636 (2 129 with cancer as underlying cause) were not regarded to be new cancers, which constitutes 4.0% of all cancers mentioned on death certificates and 39.5% of the DCNs. Inclusion of the DCI cases increased the incidence of all cancers combined by 2.6%, with largest differences for cancers with poorer prognosis and for older age groups. Without validation, including the 2 129 disregarded death certificates would over-estimate the incidence by 1.3%. Including DCI cases decreased the five-year relative survival estimate for all cancer sites combined with 0.5% points.ConclusionIn this study, almost 40% of the DCNs were regarded not to be a new cancer case, indicating unreliability of death certificate information for cancers that are not already registered from other sources. The majority of the DCNs where, however, registered as new cases that would have been missed without death certificates. Both including and excluding the DCI cases will potentially bias the survival estimates, but in different directions. This biases were shown to be small in the Cancer Registry of Norway.     

Correcting bias due to missing stage data in the non-parametric estimation of stage-specific net survival for colorectal cancer using multiple imputation

BackgroundPopulation-based net survival by tumour stage at diagnosis is a key measure in cancer surveillance. Unfortunately, data on tumour stage are often missing for a non-negligible proportion of patients and the mechanism giving rise to the missingness is usually anything but completely at random. In this setting, restricting analysis to the subset of complete records gives typically biased results. Multiple imputation is a promising practical approach to the issues raised by the missing data, but its use in conjunction with the Pohar-Perme method for estimating net survival has not been formally evaluated.MethodsWe performed a resampling study using colorectal cancer population-based registry data to evaluate the ability of multiple imputation, used along with the Pohar-Perme method, to deliver unbiased estimates of stage-specific net survival and recover missing stage information. We created 1000 independent data sets, each containing 5000 patients. Stage data were then made missing at random under two scenarios (30% and 50% missingness).ResultsComplete records analysis showed substantial bias and poor confidence interval coverage. Across both scenarios our multiple imputation strategy virtually eliminated the bias and greatly improved confidence interval coverage.ConclusionsIn the presence of missing stage data complete records analysis often gives severely biased results. We showed that combining multiple imputation with the Pohar-Perme estimator provides a valid practical approach for the estimation of stage-specific colorectal cancer net survival. As usual, when the percentage of missing data is high the results should be interpreted cautiously and sensitivity analyses are recommended.     

Effect of radiation exposure on survival after first solid cancer diagnosis in A-bomb survivors

BackgroundComparison of the estimated effect of atomic bomb radiation exposure on solid cancer incidence and solid cancer mortality in the RERF Life Span Study (LSS) reveals a difference in the magnitude and shape of the excess relative risk dose response. A possible contributing factor to this difference is pre-diagnosis radiation effect on post-diagnosis survival. Pre-diagnosis radiation exposure theoretically could influence post-diagnosis survival by affecting the genetic makeup and possibly aggressiveness of cancer, or by compromising tolerance for aggressive treatment for cancer.MethodsWe analyze the radiation effect on post-diagnosis survival in 20,463 LSS subjects diagnosed with first-primary solid cancer between 1958 and 2009 with particular attention to whether death was caused by the first-primary cancer, other cancer, or non-cancer diseases.ResultsFrom multivariable Cox regression analysis of cause-specific survival, the excess hazard at 1 Gy (EH_1Gy) for death from the first primary cancer was not significantly different from zero – p = 0.23, EH_1Gy = 0.038 (95 % CI: −0.023, 0.104). Death from other cancer and death from non-cancer diseases both were significantly associated with radiation dose: other cancer EH_1Gy = 0.38 (95 % CI: 0.24, 0.53); non-cancer EH_1Gy = 0.24 (95 % CI: 0.13, 0.36), both p < 0.001.ConclusionThere is no detectable large effect of pre-diagnosis radiation exposure on post-diagnosis death from the first primary cancer in A-bomb survivors.ImpactA direct effect of pre-diagnosis radiation exposure on cancer prognosis is ruled out as an explanation for the difference in incidence and mortality dose response in A-bomb survivors.     

Regression analysis of four physical characteristics—stature,length of thigh,length of leg and length of foot of the male population in Sichuan Province

Using four physical characteristics of 394 adult male individuals in the Sichuan Province of China — stature, length of thigh, length of leg and length of foot, a series of linear regression equations and ternary regression equations have been established. Meanwhile three stepwise regression equations also have been established including a quarternary regression equation. Generally speaking, the established multiple equations in this study should be applied as much as possible, where there are two or three independent variables, because they predict more effectively in the individual identification of forensic practice.     

Imputation of missing prostate cancer stage in English cancer registry data based on clinical assumptions

BackgroundCancer stage can be missing in national cancer registry records. We explored whether missing prostate cancer stage can be imputed using specific clinical assumptions.MethodsProstate cancer patients diagnosed between 2010 and 2013 were identified in English cancer registry data and linked to administrative hospital and mortality data (n = 139,807). Missing staging items were imputed based on specific assumptions: men with recorded N-stage but missing M-stage have no distant metastases (M0); low/intermediate-risk men with missing N- and/or M-stage have no nodal disease (N0) or metastases; and high-risk men with missing M-stage have no metastases. We tested these clinical assumptions by comparing 4-year survival in men with the same recorded and imputed cancer stage. Multi-variable Cox regression was used to test the validity of the clinical assumptions and multiple imputation.ResultsSurvival was similar for men with recorded N-stage but missing M-stage and corresponding men with M0 (89.5% vs 89.6%); for low/intermediate-risk men with missing M-stage and corresponding men with M0 (92.0% vs 93.1%); and for low/intermediate-risk men with missing N-stage and corresponding men with N0 (90.9% vs 93.7%). However, survival was different for high-risk men with missing M-stage and corresponding men with M0. Imputation based on clinical imputation performs as well as statistical multiple imputation.ConclusionSpecific clinical assumptions can be used to impute missing information on nodal involvement and distant metastases in some patients with prostate cancer.     

The completeness and timeliness of cancer registration and the implications for measuring cancer burden

BackgroundPopulation based cancer registration provides a critical role in disease surveillance in terms of incidence, survival, cancer cluster investigations and prevalence trends, and therefore high levels of completeness and timeliness are required. This study estimates completeness and variation between early and late registrations in the N. Ireland Cancer Registry (NICR) and assesses the implications for reporting cancer incidence and for registry-based research.MethodsTwo main approaches assessed completeness. For the period 2010–2012, incidence reported in the first year of data publication was compared to incidence reported in subsequent years until 2015. Demographic characteristics and survival of incident cases ascertained before the first publication year were compared to those ascertained in subsequent years. The flow method approach was used to estimate completeness annually after the incident year.ResultsOverall incidence for all cancers increased between the first year of data publication and subsequent years up to 2015, irrespective of year of diagnosis. Late registrations had poorer survival. The flow method approach estimated the completeness of case ascertainment of NICR data to be 96% complete at five years for all cancers combined.ConclusionThe estimated completeness levels for the NICR are comparable to other high quality cancer registries internationally. While data timeliness has little impact on incidence estimates, delays in registration may have implications for specific research studies into incidence and survival. This means that improvements in the timeliness of reporting should be a target for all registries but not at the expense of completeness.     

Ten-year update of the international registry on cytokine-induced killer cells in cancer immunotherapy

Cytokine-induced killer (CIK) cells represent an exceptional T-cell population uniting a T cell and natural killer cell-like phenotype in their terminally differentiated CD3⁺CD56⁺ subset, which features non-MHC-restricted tumor-killing activity. CIK cells have provided encouraging results in initial clinical studies and revealed synergistic antitumor effects when combined with standard therapeutic procedures. We established the international registry on CIK cells (IRCC) to collect and evaluate clinical trials for the treatment of cancer patients in 2010. Moreover, our registry set new standards on the reporting of results from clinical trials using CIK cells. In the present update, a total of 106 clinical trials including 10,225 patients were enrolled in IRCC, of which 4,889 patients in over 30 distinct tumor entities were treated with CIK cells alone or in combination with conventional or novel therapies. Significantly improved median progression-free survival and overall survival were shown in 27 trials, and 9 trials reported a significantly increased 5-year survival rate. Mild adverse effects and graft-versus-host diseases were also observed in the studies. Recently, more efforts have been put into the improvement of antitumoral efficacy by CIK cells including the administration of immune checkpoint inhibitors and modification with chimeric antigen receptorc. The minimal toxicity and multiple improvements on their tumor-killing activity both make CIK cells a favorable therapeutic tool in the clinical practice of cancer immunotherapy.     

The outcome of patients with serous papillary peritoneal cancer,fallopian tube cancer,and epithelial ovarian cancer by treatment eras: 27 years data from the SEER registry

AimTo determine the differential effect of the treatment periods on the survival of patients with stage IV serous papillary peritoneal carcinoma (SPPC), fallopian tube cancers, and epithelial ovarian cancers (EOC).MethodsThis was an exploratory, population-based observational study of all patients with stage IV SPPC, fallopian tube cancers, and EOC collected from the SEER Research Data 1973–2017. The study period was divided into three time-periods: platinum combinations before the taxane era (1990–1995), platinum plus taxane chemotherapy era (1996–2013), and bevacizumab era (2014–2017).ResultsA total of 9828 patients were eligible for analyses: SPPC (3898 patients; 39.7%), fallopian tube cancers (1290 patients; 13.1%) and EOC (4640 patients, 47.2%). In the 1990–1995 era, the 3-year cause-specific survival was 40% for SPPC, 53% for fallopian tube cancers, and 40% for POC. In the following era 1993–2013, the 3-year cause-specific survival increased to 55% for SPPC, 74% for fallopian tube cancers, and 45% for POC. The last era 2014–2017 showed a 3-year cause-specific survival of 64%, 67%, and 45% for patients with SPPC, fallopian tube cancers, and POC, respectively. The differences in cause-specific survival were statistically significant for patients with SPPC (p=0.004). Multivariable analysis showed that the treatment eras and age at diagnosis were associated with cause-specific survival.ConclusionThe results of this study are hypothesis-generating and cannot be considered conclusive given the inherent limitations of registry analysis. Subgroup analyses of the phase III randomized controlled trials, by tumor subset (EOC, fallopian tube cancer, and SPPC) would shed more light on the differential effects of novel therapies.     

Breast and colorectal cancer recurrence-free survival estimates in the US: Modeling versus active data collection

BackgroundA modeling method was developed to estimate recurrence-free survival using cancer registry survival data. This study aims to validate the modeled recurrence-free survival against “gold-standard” estimates from data collected by the National Program of Cancer Registries (NPCR) Patient-Centered Outcomes Research (PCOR) project.MethodsWe compared 5-year metastatic recurrence-free survival using modeling and empirical estimates from the PCOR project that collected disease-free status, tumor progression and recurrence for colorectal and female breast cancer cases diagnosed in 2011 in 5 U.S. state registries. To estimate empirical recurrence-free survival, we developed an algorithm that combined disease-free, recurrence, progression, and date information from NPCR-PCOR data. We applied the modeling method to relative survival for patients diagnosed with female breast and colorectal cancer in 2000–2015 in the SEER-18 areas.ResultsWhen grouping patients with stages I-III, the 5-year metastatic recurrence-free modeled and NPCR-PCOR estimates are very similar being respectively, 90.2 % and 88.6 % for female breast cancer, 74.6 % and 75.3 % for colon cancer, and 68.8 % and 68.5 % for rectum cancer. In general, the 5-year recurrence-free NPCR-PCOR and modeled estimates are still similar when controlling by stage. The modeled estimates, however, are not as accurate for recurrence-free survival in years 1–3 from diagnosis.ConclusionsThe alignment between NPCR-PCOR and modeled estimates supports their validity and provides robust population-based estimates of 5-year metastatic recurrence-free survival for female breast, colon, and rectum cancers. The modeling approach can in principle be extended to other cancer sites to provide provisional population-based estimates of 5-year recurrence free survival.     

Accuracy and completeness of the New Zealand Cancer Registry for staging of invasive breast cancer

PurposePopulation based cancer registries are an invaluable resource for monitoring incidence and mortality for many types of cancer. Research and healthcare decisions based on cancer registry data rely on the case completeness and accuracy of recorded data. This study was aimed at assessing completeness and accuracy of breast cancer staging data in the New Zealand Cancer Registry (NZCR) against a regional breast cancer register.MethodologyData from 2562 women diagnosed with invasive primary breast cancer between 1999 and 2011 included in the Waikato Breast Cancer Register (WBCR) were used to audit data held on the same individuals by the NZCR. WBCR data were treated as the benchmark.ResultsOf 2562 cancers, 315(12.3%) were unstaged in the NZCR. For cancers with a known stage in the NZCR, staging accuracy was 94.4%. Lower staging accuracies of 74% and 84% were noted for metastatic and locally invasive (involving skin or chest wall) cancers, respectively, compared with localized (97%) and lymph node positive (94%) cancers. Older age (>80 years), not undergoing therapeutic surgery and higher comorbidity score were significantly (p < 0.01) associated with unstaged cancer. The high proportion of unstaged cancer in the NZCR was noted to have led to an underestimation of the true incidence of metastatic breast cancer by 21%. Underestimation of metastatic cancer was greater for Māori (29.5%) than for NZ European (20.6%) women. Overall 5-year survival rate for unstaged cancer (NZCR) was 55.9%, which was worse than the 5-year survival rate for regional (77.3%), but better than metastatic (12.9%) disease.ConclusionsUnstaged cancer and accuracy of cancer staging in the NZCR are major sources of bias for the NZCR based research. Improving completeness and accuracy of staging data and increasing the rate of TNM cancer stage recording are identified as priorities for strengthening the usefulness of the NZCR.     

Five-year relative survival and determinants of excess mortality in patients with head and neck and thyroid cancers: A population-based study from Golestan province,Northern Iran

BackgroundWe aimed to assess relative survival (RS) and determinants of excess mortality rate in patients with head and neck squamous cell carcinomas (HNSCC) and thyroid cancer in Golestan province, Northern Iran.MethodsWe recruited new primary HNSCC and thyroid cancer cases from Golestan, 2006–2016. Five-year age-standardized RS with their 95% confidence intervals (CIs) were calculated. The relationships between different variables with excess mortality rates were assessed by estimating adjusted excess hazard ratios (aEHRs) with their 95% CIs.ResultsOverall, 718 cases of HNSCC and 386 thyroid cancer cases were enrolled. Five-year age-standardized RS (95% CI) were 36% (31−41) and 61% (52−69) in HNSCC and thyroid cancer patients, respectively. There were significant relationship between excess mortality rates in HNSCC patients with metastasis (aEHR= 3.31; 95%CI: 2.26–4.84), treatment type (4.19; 2.54–6.91, for no treatment as compared to receiving both surgery and chemoradiotherapy), age (2.16; 1.57–2.96, for older age group) and smoking (2.00; 1.45–2.75, for smokers as compared to non-smokers). Determinant of the excess mortality in thyroid cancer patients included metastasis (19.65; 8.08–47.79), tumor morphology (12.27; 4.62–32.58, for anaplastic cancer as compared to papillary cancer), treatment type (8.95, 4.13–19.4, for no treatment as compared to receiving both surgery and iodine therapy) and age (2.31; 1.17–4.54, for older age group).ConclusionOur findings suggested low RS for thyroid cancer in our population, while the estimates for HNSCC were comparable with other population. Metastasis, treatment type and age were determinants of mortality both in thyroid and HNSCC patients.     

Capture method affects survival estimates and subsequent interpretation of ecological covariates for a long‐lived cervid

Understanding what variables affect ungulate neonate survival is imperative to successful conservation and management of the species. Predation is commonly cited as a cause‐specific source of mortality, and ecological covariates often influence neonate survival. However, variation in survival estimates related to capture methodology has been documented with opportunistically captured neonates generally displaying greater survival than those captured via aid of vaginal implant transmitters (VITs), likely because of increased left truncation observed in the opportunistically captured datasets. Our goal was to assess whether 3‐ and 6‐month survival estimates varied by capture method while simultaneously assessing whether capture method affected model selection and interpretation of ecological covariates for white‐tailed deer neonates captured from three study sites from 2014 to 2015 in North Dakota and South Dakota, USA. We found survival varied by capture method for 3‐month neonate survival with opportunistically captured neonates displaying up to 26% greater survival than their counterparts captured via VITs; however, this relationship was not present for 6‐month survival. We also found model selection and subsequent interpretation of ecological covariates varied when analyzing datasets comprised of neonates captured via VITs, neonates captured opportunistically, and all neonates combined regardless of capture method. When interpreting results from our VIT‐only analysis for 3‐month survival, we found survival varied by three time intervals and was lowest in the first two weeks of life. Capture method did not affect 6‐month survival, which was most influenced by total precipitation occurring during 3 – 8 weeks of a neonate''s life and percent canopy cover found at a neonate''s capture site. Our results support previous research that capture method must be accounted for when deriving survival estimates for ungulate neonates as it can impact derived estimates and subsequent interpretation of results.     

Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

Lysosomal integral membrane protein-2 (LIMP2) is an important component of innate immunity. However, its role in the anti-tumor response remains unknown. Here, we found that the level of LIMP2 mRNA was frequently upregulated in gastric cancer (GC) tissues according to the TCGA, which was confirmed by immunohistochemistry in 329 cases. LIMP2 expression was significantly associated with Lauren classification (P=0.042), depth of invasion (P=0.016), lymph node metastasis (P=0.039) and TNM stage (P=0.027). LIMP2 expression (P < 0.001), differentiation (P < 0.001), TNM stage (P < 0.001) and preoperative CEA (P=0.018) can be used as independent prognostic factors. GC patients with higher levels of LIMP2 mRNA experienced improved clinical outcomes. Mechanically, the TGF-β signaling pathway, the ERBB signaling pathway, and Toll-like receptor signaling were enriched in proteins with higher LIMP2. Moreover, LIMP2 expression was positively related with M1 tumor-associated macrophages (TAMs) in TCGA data, which was verified by capturing LIMP2 and CD86 co-expression in GC samples. The study suggests that LIMP2 expression in GC would predict improved outcomes with M1 TAMs infiltration.     

Patterns of cancer in geographic and endogamous subdivisions of the Hutterite Brethren of Canada

The Hutterite Brethren comprise a religious isolate and live on communal agricultural farms (colonies) in North America. In 1976 there were approximately 15,000 Canadian Brethren living in 179 colonies of the three endogamous subdivisions, the Dariusleut, Lehrerleut, and Schmiedeleut. Dariusleut and Lehrerleut colonies are located in both Alberta and Saskatchewan, and the Schmiedeleut are in Manitoba. Brethren were identified on population-based cancer registries of the three Prairie Provinces and among death registrations in the vital statistics of Alberta and Saskatchewan. The method of ascertainment was by a search for the 15 contemporary surnames and verification by address. 89 male and 91 female Brethren were identified who had cancer during the period, 1956--1975. The numbers of observed cancers were less than expected from provincial incidence rates for males and females in each province. The largest deficits were for female Brethren in Manitoba and Saskatchewan. There is a marked deficiency of cancer of the uterine cervix among female Brethren. In males there is a significant deficit of lung cancer. The Hutterite way of life contributes to a low risk for cancers of smoking-associated sites. However, there is evidence that male Brethren in Alberta may be at relatively increased risk for stomach cancer and leukemias. The site distribution patterns of cancers among the three endogamous leut are similar.