Estimates of the worldwide incidence and mortality from 27 major cancers and for all cancers combined for 2012 are now available in the GLOBOCAN series of the International Agency for Research on ...Cancer. We review the sources and methods used in compiling the national cancer incidence and mortality estimates, and briefly describe the key results by cancer site and in 20 large “areas” of the world. Overall, there were 14.1 million new cases and 8.2 million deaths in 2012. The most commonly diagnosed cancers were lung (1.82 million), breast (1.67 million), and colorectal (1.36 million); the most common causes of cancer death were lung cancer (1.6 million deaths), liver cancer (745,000 deaths), and stomach cancer (723,000 deaths).
What's new?
In this report, we present the most recent cancer incidence and mortality statistics (for 2012) for the major cancers in 20 regions of the world. Details of the data sources and methods used in GLOBOCAN to compile the estimates at the national level are provided, and we introduce a novel alphanumeric scoring system to give a broad indication of the robustness of the estimation within each country. A global snapshot of the patterns by cancer site brings focus to the need for regional prioritisation of cancer control efforts, as well as the ongoing efforts to improve the limited surveillance systems in many low and middle income countries.
AbstractObjectiveTo test the efficacy of screening by clinical breast examination in downstaging breast cancer at diagnosis and in reducing mortality from the disease, when compared with no ...screening.DesignProspective, cluster randomised controlled trial.Setting20 geographically distinct clusters located in Mumbai, India, randomly allocated to 10 screening and 10 control clusters; total trial duration was 20 years (recruitment began in May 1998; database locked in March 2019 for analysis).Participants151 538 women aged 35-64 with no history of breast cancer.InterventionsWomen in the screening arm (n=75 360) received four screening rounds of clinical breast examination (conducted by trained female primary health workers) and cancer awareness every two years, followed by five rounds of active surveillance every two years. Women in the control arm (n=76 178) received one round of cancer awareness followed by eight rounds of active surveillance every two years.Main outcome measuresDownstaging of breast cancer at diagnosis and reduction in mortality from breast cancer.ResultsBreast cancer was detected at an earlier age in the screening group than in the control group (age 55.18 (standard deviation 9.10) v 56.50 (9.10); P=0.01), with a significant reduction in the proportion of women with stage III or IV disease (37% (n=220) v 47% (n=271), P=0.001). A non-significant 15% reduction in breast cancer mortality was observed in the screening arm versus control arm in the overall study population (age 35-64; 20.82 deaths per 100 000 person years (95% confidence interval 18.25 to 23.97) v 24.62 (21.71 to 28.04); rate ratio 0.85 (95% confidence interval 0.71 to 1.01); P=0.07). However, a post hoc subset analysis showed nearly 30% relative reduction in breast cancer mortality in women aged 50 and older (24.62 (20.62 to 29.76) v 34.68 (27.54 to 44.37); 0.71 (0.54 to 0.94); P=0.02), but no significant reduction in women younger than 50 (19.53 (17.24 to 22.29) v 21.03 (18.97 to 23.44); 0.93 (0.79 to 1.09); P=0.37). A 5% reduction in all cause mortality was seen in the screening arm versus the control arm, but it was not statistically significant (rate ratio 0.95 (95% confidence interval 0.81 to 1.10); P=0.49).ConclusionsThese results indicate that clinical breast examination conducted every two years by primary health workers significantly downstaged breast cancer at diagnosis and led to a non-significant 15% reduction in breast cancer mortality overall (but a significant reduction of nearly 30%in mortality in women aged ≥50). No significant reduction in mortality was seen in women younger than 50 years. Clinical breast examination should be considered for breast cancer screening in low and middle income countries.Trial registrationClinical Trials Registry of India CTRI/2010/091/001205; ClinicalTrials.gov NCT00632047.
Despite conventional treatment modalities, gallbladder cancer (GBC) remains a highly lethal malignancy. Prognostic biomarkers and effective adjuvant immunotherapy for GBC are not available. In the ...recent past, immunotherapeutic approaches targeting tumor associated inflammation have gained importance but the mediators of inflammatory circuit remain unexplored in GBC patients. In the current prospective study, we investigated the role of IL17 producing TCR gamma delta super(+) (T gamma delta 17), CD4 super(+) (Th17), CD8 super(+) (Tc17) and regulatory T cells (Tregs) in pathogenesis of GBC. Analysis by multi-color flow cytometry revealed that compared to healthy individuals (HI), T gamma delta 17, Th17 and Tc17 cells were increased in peripheral blood mononuclear cells (PBMCs) and tumor infiltrating lymphocytes (TIL) of GBC patients. Tregs were decreased in PBMCs but increased in TILs of GBC patients. The suppressive potential of Tregs from GBC patients and HI were comparable. Serum cytokines profile of GBC patients showed elevated levels of cytokines (IL6, IL23 and IL1 beta ) required for polarization and/or stabilization of IL17 producing cells. We demonstrated that T gamma delta 17 cells migrate toward tumor bed using CXCL9-CXCR3 axis. IL17 secreted by T gamma delta 17 induced productions of vascular endothelial growth factor and other angiogenesis related factors in GBC cells. T gamma delta 17 cells promote vasculogenesis as studied by chick chorioallantoic membrane assay. Survival analysis showed that T gamma delta 17, Th17 and Treg cells in peripheral blood were associated with poor survival of GBC patients. Our findings suggest that T gamma delta 17 is a protumorigenic subtype of gamma delta T cells which induces angiogenesis. T gamma delta 17 may be considered as a predictive biomarker in GBC thus opening avenues for targeted therapies. What's new? Human T cells expressing gamma delta -TCR exhibit potent anti-tumor activity and are potential candidates for cell-based therapies. Evidence however also exists of the ability of gamma delta -TCR cells to suppress anti-tumor responses, making deeper insight necessary for the successful clinical application of gamma delta T cell-based immunotherapies. This study identified IL17-producing gamma delta T cells (T gamma delta 17) as a pro-tumorigenic subtype of gamma delta T cells associated with poor survival in gallbladder cancer (GBC) patients. T gamma delta 17 cells infiltrate the tumor bed via CXCL9-CXCR3 axis and IL17 induces pro-angiogenic factors in GBC cells. T gamma delta 17 may be considered as a predictive biomarker in GBC, opening up new avenues for targeted therapies.
Background
HER-(human epidermal growth factor receptor 2) gene amplification and protein overexpression are important predictive, prognosis markers, and therapeutic target for breast cancer, ...emphasizing the importance of categorizing patients into HER2 positive and negative. However, from immunohistochemistry scores, 2% patients are neither HER2 + nor -ve, but borderline called HER2B. To make informed treatment decisions of these patients, it is important to know how different this group is compared to HER-2 positive/negative.
Methods
We analyzed n = 104,668 breast cancer patient samples from Surveillance, Epidemiology, and End Results (SEER) database. Survival analysis was performed using open source R (Cran project R version 3.5.0) “survival” package. Hazard ratio with confidence intervals was computed using coxph function.
Results
Of
n
= 104,668, 2239 (2.13%) patients were HER2 borderline, 87,157 (83.26%) HER2-negative, and 15,272 (14.6%) HER2-positive. The breast cancer as primary malignancy was observed in 84,944 (81.16%) patients. In primary malignant breast cancer (PMBC) patients, the hazard ratio among HER2-negative patients was significantly higher than HER2-positive patient samples (HR = 0.772, 95% CI 0.715–0.833,
p
= < .001), whereas HER2 negative status was not significantly favorable in PMBC negative patients in HER2-positive (HR = .919, 95% 0.797–1.06,
p
= .248). Most importantly in PMBC patients, the HR for HER2-borderline was poor in comparison to HER2 negative (HR = 1.354, 95% CI 1.126–1.627,
p
= < .001).
Conclusion
This is the first report with large cohort of patient samples and significant statistical power to demonstrate that HER2 borderline represents a negative prognostic factor for PMBC. Thus providing rationale for controlled clinical trial for HER2-targeted therapies in HER2-borderline patients.
In this large case–control study in India, the prevalence of smoking was about 5% among women and 37% among men between the ages of 30 and 69 years. Smoking was associated with increased mortality ...from tuberculosis, respiratory disease, cardiovascular disease, and cancer.
In this study, the prevalence of smoking was about 5% among women and 37% among men between the ages of 30 and 69 years. Smoking was associated with increased mortality from tuberculosis, respiratory disease, cardiovascular disease, and cancer.
India is a diverse country, with marked regional variation in lifestyles and in the main causes of death.
1
Among adults, most deaths are from respiratory, vascular, or neoplastic disease or from tuberculosis; the death rates from these diseases can be increased by smoking.
2
In recent years, large household surveys have shown that in middle age, more than one third of men and a few percent of women smoke tobacco and that there are about 120 million smokers in India.
3
,
4
Tobacco is commonly consumed in the form of bidis, which are smaller than cigarettes and typically contain only about a . . .
Despite conventional treatment modalities, gallbladder cancer (GBC) remains a highly lethal malignancy. Prognostic biomarkers and effective adjuvant immunotherapy for GBC are not available. In the ...recent past, immunotherapeutic approaches targeting tumor associated inflammation have gained importance but the mediators of inflammatory circuit remain unexplored in GBC patients. In the current prospective study, we investigated the role of IL17 producing TCRγδ+ (Tγδ17), CD4+ (Th17), CD8+ (Tc17) and regulatory T cells (Tregs) in pathogenesis of GBC. Analysis by multi‐color flow cytometry revealed that compared to healthy individuals (HI), Tγδ17, Th17 and Tc17 cells were increased in peripheral blood mononuclear cells (PBMCs) and tumor infiltrating lymphocytes (TIL) of GBC patients. Tregs were decreased in PBMCs but increased in TILs of GBC patients. The suppressive potential of Tregs from GBC patients and HI were comparable. Serum cytokines profile of GBC patients showed elevated levels of cytokines (IL6, IL23 and IL1β) required for polarization and/or stabilization of IL17 producing cells. We demonstrated that Tγδ17 cells migrate toward tumor bed using CXCL9‐CXCR3 axis. IL17 secreted by Tγδ17 induced productions of vascular endothelial growth factor and other angiogenesis related factors in GBC cells. Tγδ17 cells promote vasculogenesis as studied by chick chorioallantoic membrane assay. Survival analysis showed that Tγδ17, Th17 and Treg cells in peripheral blood were associated with poor survival of GBC patients. Our findings suggest that Tγδ17 is a protumorigenic subtype of γδT cells which induces angiogenesis. Tγδ17 may be considered as a predictive biomarker in GBC thus opening avenues for targeted therapies.
What's new?
Human T cells expressing γδ‐TCR exhibit potent anti‐tumor activity and are potential candidates for cell‐based therapies. Evidence however also exists of the ability of γδ‐TCR cells to suppress anti‐tumor responses, making deeper insight necessary for the successful clinical application of γδT cell‐based immunotherapies. This study identified IL17‐producing γδT cells (Tγδ17) as a pro‐tumorigenic subtype of γδT cells associated with poor survival in gallbladder cancer (GBC) patients. Tγδ17 cells infiltrate the tumor bed via CXCL9‐CXCR3 axis and IL17 induces pro‐angiogenic factors in GBC cells. Tγδ17 may be considered as a predictive biomarker in GBC, opening up new avenues for targeted therapies.
Summary Background The age-specific mortality rates and total deaths from specific cancers have not been documented for the various regions and subpopulations of India. We therefore assessed the ...cause of death in 2001–03 in homes in small areas that were chosen to be representative of all the parts of India. Methods At least 130 trained physicians independently assigned causes to 122 429 deaths, which occurred in 1·1 million homes in 6671 small areas that were randomly selected to be representative of all of India, based on a structured non-medical surveyor's field report. Findings 7137 of 122 429 study deaths were due to cancer, corresponding to 556 400 national cancer deaths in India in 2010. 395 400 (71%) cancer deaths occurred in people aged 30–69 years (200 100 men and 195 300 women). At 30–69 years, the three most common fatal cancers were oral (including lip and pharynx, 45 800 22·9%), stomach (25 200 12·6%), and lung (including trachea and larynx, 22 900 11·4%) in men, and cervical (33 400 17·1%), stomach (27 500 14·1%), and breast (19 900 10·2%) in women. Tobacco-related cancers represented 42·0% (84 000) of male and 18·3% (35 700) of female cancer deaths and there were twice as many deaths from oral cancers as lung cancers. Age-standardised cancer mortality rates per 100 000 were similar in rural (men 95·6 99% CI 89·6–101·7 and women 96·6 90·7–102·6) and urban areas (men 102·4 92·7–112·1 and women 91·2 81·9–100·5), but varied greatly between the states, and were two times higher in the least educated than in the most educated adults (men, illiterate 106·6 97·4–115·7 vs most educated 45·7 37·8–53·6; women, illiterate 106·7 99·9–113·6 vs most educated 43·4 30·7–56·1). Cervical cancer was far less common in Muslim than in Hindu women (study deaths 24, age-standardised mortality ratio 0·68 0·64–0·71 vs 340, 1·06 1·05–1·08). Interpretation Prevention of tobacco-related and cervical cancers and earlier detection of treatable cancers would reduce cancer deaths in India, particularly in the rural areas that are underserved by cancer services. The substantial variation in cancer rates in India suggests other risk factors or causative agents that remain to be discovered. Funding Bill & Melinda Gates Foundation and US National Institutes of Health.
Past history of gallstones is associated with increased risk of gallbladder cancer in observational studies. We conducted complementary observational and Mendelian randomization (MR) analyses to ...determine whether history of gallstones is causally related to development of gallbladder cancer in an Indian population.
To investigate associations between history of gallstones and gallbladder cancer, we used questionnaire and imaging data from a gallbladder cancer case-control study conducted at Tata Memorial Hospital, Mumbai, Maharashtra, India (cases = 1,170; controls = 2,525). We then used 26 genetic variants identified in a genome-wide association study of 27,174 gallstone cases and 736,838 controls of European ancestry in an MR approach to assess causality. The association of these genetic variants with both gallstones and gallbladder cancer was examined in the gallbladder cancer case-control study. Various complementary MR approaches were used to evaluate the robustness of our results in the presence of pleiotropy and heterogeneity, and to consider the suitability of the selected SNPs as genetic instruments for gallstones in an Indian population.
We found a strong observational association between gallstones and gallbladder cancer using self-reported history of gallstones OR = 4.5; 95% confidence interval (CI) = 3.5-5.8 and with objective measures of gallstone presence using imaging techniques (OR = 2.0; 95% CI = 1.5-2.7). We found consistent causal estimates across all MR techniques, with ORs for gallbladder cancer in the range of 1.3-1.6.
Our findings indicate a causal relationship between history of gallstones and increased risk of gallbladder cancer, albeit of a smaller magnitude than those found in observational analysis.
Our findings emphasize the importance of gallstone treatment for preventing gallbladder cancer in high-risk individuals.
Summary Background Gallbladder cancer is highly lethal, with notable differences in incidence by geography and ethnic background. The aim of this study was to identify common genetic susceptibility ...alleles for gallbladder cancer. Methods In this case-control genome-wide association study (GWAS), we did a genome-wide scan of gallbladder cancer cases and hospital visitor controls, both of Indian descent, followed by imputation across the genome. Cases were patients aged 20–80 years with microscopically confirmed primary gallbladder cancer diagnosed or treated at Tata Memorial Hospital, Mumbai, India, and enrolled in the study between Sept 12, 2010, and June 8, 2015. We only included patients who had been diagnosed less than 1 year before the date of enrolment and excluded patients with any other malignancies. We recruited visitor controls aged 20–80 years with no history of cancer visiting all departments or units of Tata Memorial Hospital during the same time period and frequency matched them to cases on the basis of age, sex, and current region of residence. We estimated association using logistic regression, adjusting for age, sex, and five eigenvectors. We recruited samples for a replication cohort from patients visiting Tata Memorial Hospital between Aug 4, 2015, and May 17, 2016, and patients visiting the Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India, between July, 2010, and May, 2015. We used the same inclusion and exclusion criteria for the replication set. We examined three of the most significant single-nucleotide polymorphisms (SNPs) in the replication cohort and did a meta-analysis of the GWAS discovery and replication sets to get combined estimates of association. Findings The discovery cohort comprised 1042 gallbladder cancer cases and 1709 controls and the replication cohort contained 428 gallbladder cancer cases and 420 controls. We observed genome-wide significant associations for several markers in the chromosomal region 7q21.12 harbouring both the ABCB1 and ABCB4 genes, with the most notable SNPs after replication and meta-analysis being rs1558375 (GWAS p=3·8 × 10−9 ; replication p=0·01; combined p=2·3 × 10−10 ); rs17209837 (GWAS p=2·0 × 10−8 ; replication p=0·02; combined p=2·3 × 10−9 ), and rs4148808 (GWAS p=2·4 × 10−8 ; replication p=0·008; combined p=2·7 × 10−9 ). Combined estimates of per-allele trend odds ratios were 1·47 (95% CI 1·30–1·66; p=2·31 × 10−10 ) for rs1558375, 1·61 (1·38–1·89; p=2·26 × 10−9 ) for rs17209837, and 1·57 (1·35–1·82; p=2·71 × 10−9 ) for rs4148808. GWAS heritability analysis suggested that common variants are associated with substantial variation in risk of gallbladder cancer (sibling relative risk 3·15 95% CI 1·80–5·49). Interpretation To our knowledge, this study is the first report of common genetic variation conferring gallbladder cancer risk at genome-wide significance. This finding, along with in-silico and biological evidence indicating the potential functional significance of ABCB1 and ABCB4 , underlines the likely importance of these hepatobiliary phospholipid transporter genes in the pathology of gallbladder cancer. Funding The Tata Memorial Centre and Department of Biotechnology.
There is a scarcity of population-based prostate cancer survival data in India. We assessed the population-based, overall survival of patients with prostate cancer from the Sangrur and Mansa cancer ...registries of the Punjab state, India.
In the year 2013-2016, a total of 171 prostate cancer cases were registered in these two registries. Based on these registries, survival analysis was performed using the date of diagnosis as the starting date and the last follow-up date being December 31, 2021 or the date of death. Survival was calculated using STATA software. Relative survival was calculated using the Pohar Perme method.
Follow up was available for all the registered cases. Of the 171 cases, 41 (24%) were alive and 130 (76.0%) were dead. Of the prescribed treatments, 106 (62.7%) cases completed the treatment and 63 (37.3%) cases did not complete the treatment. Overall, 5-year age-standardized prostate cancer relative survival was 30.3%. Patients who completed the treatment had a 7.8 times higher 5-year relative survival (45.5%) compared to those who did not (5.8%). The difference between the two groups is statistically significant (hazard ratio 0.16, 95% confidence interval 0.10-0.27).
To improve survival, we need to raise awareness in the community and among primary physicians so that prostate cancer cases can reach the hospital early and should be treated effectively. The cancer center should develop the systems in their hospital so that there will be no hurdles to the patients in treatment completion. We found a low overall relative survival among patients of prostate cancer in these two registries. Patients who received treatment had a significantly higher survival.
PDF
