The International Collaboration for Research methods Development in Oncology (CReDO) workshops: shaping the future of global oncology research.

Low-income and middle-income countries (LMICs) have a disproportionately high burden of cancer and cancer mortality. The unique barriers to optimum cancer care in these regions necessitate context-specific research. The conduct of research in LMICs has several challenges, not least of which is a paucity of formal training in research methods. Building capacity by training early career researchers is essential to improve research output and cancer outcomes in LMICs. The International Collaboration for Research methods Development in Oncology (CReDO) workshop is an initiative by the Tata Memorial Centre and the National Cancer Grid of India to address gaps in research training and increase capacity in oncology research. Since 2015, there have been five CReDO workshops, which have trained more than 250 oncologists from India and other countries in clinical research methods and protocol development. Participants from all oncology and allied fields were represented at these workshops. Protocols developed included clinical trials, comparative effectiveness studies, health services research, and observational studies, and many of these protocols were particularly relevant to cancer management in LMICs. A follow-up of these participants in 2020 elicited an 88% response rate and showed that 42% of participants had made progress with their CReDO protocols, and 73% had initiated other research protocols and published papers. In this Policy Review, we describe the challenges to research in LMICs, as well as the evolution, structure, and impact of CReDO and other similar workshops on global oncology research.

Mustard oil consumption, cooking method, diet and gallbladder cancer risk in high- and low-risk regions of India.

The current study aimed to investigate the role of cooking with mustard oil and other dietary factors in relation to gallbladder cancer (GBC) in high- and low-incidence regions of India. A case-control study was conducted including 1,170 histologically confirmed cases and 2,525 group-matched visitor controls from the largest cancer hospital in India. Dietary data were collected through a food frequency questionnaire. For oil consumption, we enquired about monthly consumption of 11 different types of cooking oil per family and the number of individuals usually sharing the meal to estimate per-individual consumption of oil. Information about method of cooking was also requested. Odds ratios (ORs) and 95% confidence intervals (CIs) quantifying the association of GBC risk consumption of different types of oil, method of cooking, and dietary food items, were estimated using logistic regression models, after adjusting for potential confounders. High consumption of mustard oil was associated with GBC risk in both high- and low-risk regions (OR = 1.33, 95% CI = 0.99-1.78; OR = 3.01, 95% CI = 1.66-5.45), respectively. An increased risk of GBC was observed with deep frying of fresh fish in mustard oil (OR = 1.57, 95% CI = 0.99-2.47, p-value = 0.052). A protective association was observed with consumption of leafy vegetables, fruits, onion and garlic. No association was observed between consumption of meat, spicy food, turmeric, pulses or with any other oil as a cooking medium. The effect of high consumption of mustard oil on GBC risk, if confirmed, has implications for the primary prevention of GBC, via a reduced consumption.

Current status of human papillomavirus vaccination in India's cervical cancer prevention efforts.

Efforts are being made to scale up human papillomavirus (HPV) vaccination for adolescent girls in India. Bivalent and quadrivalent HPV vaccines were licensed in the country in 2008, and a nonavalent vaccine was licensed in 2018. Demonstration projects initiated in Andhra Pradesh and Gujarat in 2009 introduced HPV vaccination in public health services in India. Following a few deaths in these projects, although subsequently deemed unrelated to vaccination, HPV vaccination in research projects was suspended. This suspension by default resulted in some participants in a trial evaluating two versus three doses receiving only one dose. Since 2016, the successful introduction of HPV vaccination in immunisation programmes in Punjab and Sikkim (with high coverage and safety), government-sponsored opportunistic vaccination in Delhi, prospects of a single dose providing protection, and future availability of an affordable Indian vaccine shows promise for future widespread implementation and evaluation of HPV vaccination in India.

Cancer risks associated with external radiation from diagnostic imaging procedures.

The 600% increase in medical radiation exposure to the US population since 1980 has provided immense benefit, but increased potential future cancer risks to patients. Most of the increase is from diagnostic radiologic procedures. The objectives of this review are to summarize epidemiologic data on cancer risks associated with diagnostic procedures, describe how exposures from recent diagnostic procedures relate to radiation levels linked with cancer occurrence, and propose a framework of strategies to reduce radiation from diagnostic imaging in patients. We briefly review radiation dose definitions, mechanisms of radiation carcinogenesis, key epidemiologic studies of medical and other radiation sources and cancer risks, and dose trends from diagnostic procedures. We describe cancer risks from experimental studies, future projected risks from current imaging procedures, and the potential for higher risks in genetically susceptible populations. To reduce future projected cancers from diagnostic procedures, we advocate the widespread use of evidence-based appropriateness criteria for decisions about imaging procedures; oversight of equipment to deliver reliably the minimum radiation required to attain clinical objectives; development of electronic lifetime records of imaging procedures for patients and their physicians; and commitment by medical training programs, professional societies, and radiation protection organizations to educate all stakeholders in reducing radiation from diagnostic procedures.

Population-based cancer screening programmes in low-income and middle-income countries: regional consultation of the International Cancer Screening Network in India.

The reductions in cancer morbidity and mortality afforded by population-based cancer screening programmes have led many low-income and middle-income countries to consider the implementation of national screening programmes in the public sector. Screening at the population level, when planned and organised, can greatly benefit the population, whilst disorganised screening can increase costs and reduce benefits. The International Cancer Screening Network (ICSN) was created to share lessons, experience, and evidence regarding cancer screening in countries with organised screening programmes. Organised screening programmes provide screening to an identifiable target population and use multidisciplinary delivery teams, coordinated clinical oversight committees, and regular review by a multidisciplinary evaluation board to maximise benefit to the target population. In this Series paper, we report outcomes of the first regional consultation of the ICSN held in Agartala, India (Sept 5-7, 2016), which included discussions from cancer screening programmes from Denmark, the Netherlands, USA, and Bangladesh. We outline six essential elements of population-based cancer screening programmes, and share recommendations from the meeting that policy makers might want to consider before implementation.

Harnessing genomics to improve outcomes for women with cancer in India: key priorities for research.

Cumulatively, breast, cervical, ovarian, and uterine cancer account for more than 70% of cancers in women in India. Distinct differences in the clinical presentation of women with cancer suggest underlying differences in cancer biology and genetics. The peak age of onset of breast and ovarian cancer appears to be a decade earlier in India (age 45-50 years) than in high-income countries (age >60 years). Understanding these differences through research to develop diagnosis, screening, prevention, and treatment frameworks that ar e specific to the Indian population are critical and essential to improving women's health in India. Since the sequencing of the human genome in 2001, applications of advanced technologies, such as massively parallel sequencing, have transformed the understanding of the genetic and environmental drivers of cancer. How can advanced technologies be harnessed to provide health-care solutions at a scale and to a budget suitable for a country of 1·2 billion people? What research programmes are necessary to answer questions specific to India, and to build capacity for innovative solutions using these technologies? In order to answer these questions, we convened a workshop with key stakeholders to address these issues. In this Series paper, we highlight challenges in tackling the growing cancer burden in India, discuss ongoing genomics research and developments in infrastructure, and suggest key priorities for future research in cancer in India.

Age-specific genome-wide association study in glioblastoma identifies increased proportion of 'lower grade glioma'-like features associated with younger age.

Glioblastoma (GBM) is the most common malignant brain tumor in the United States. Incidence of GBM increases with age, and younger age-at-diagnosis is significantly associated with improved prognosis. While the relationship between candidate GBM risk SNPs and age-at-diagnosis has been explored, genome-wide association studies (GWAS) have not previously been stratified by age. Potential age-specific genetic effects were assessed in autosomal SNPs for GBM patients using data from four previous GWAS. Using age distribution tertiles (18-53, 54-64, 65+) datasets were analyzed using age-stratified logistic regression to generate p values, odds ratios (OR), and 95% confidence intervals (95%CI), and then combined using meta-analysis. There were 4,512 total GBM cases, and 10,582 controls used for analysis. Significant associations were detected at two previously identified SNPs in 7p11.2 (rs723527 [p54-63 = 1.50x10-9 , OR54-63 = 1.28, 95%CI54-63 = 1.18-1.39; p64+ = 2.14x10-11 , OR64+ = 1.32, 95%CI64+ = 1.21-1.43] and rs11979158 [p54-63 = 6.13x10-8 , OR54-63 = 1.35, 95%CI54-63 = 1.21-1.50; p64+ = 2.18x10-10 , OR64+ = 1.42, 95%CI64+ = 1.27-1.58]) but only in persons >54. There was also a significant association at the previously identified lower grade glioma (LGG) risk locus at 8q24.21 (rs55705857) in persons ages 18-53 (p18-53 = 9.30 × 10-11 , OR18-53 = 1.76, 95%CI18-53 = 1.49-2.10). Within The Cancer Genome Atlas (TCGA) there was higher prevalence of 'LGG'-like tumor characteristics in GBM samples in those 18-53, with IDH1/2 mutation frequency of 15%, as compared to 2.1% [54-63] and 0.8% [64+] (p = 0.0005). Age-specific differences in cancer susceptibility can provide important clues to etiology. The association of a SNP known to confer risk for IDH1/2 mutant glioma and higher prevalence of IDH1/2 mutation within younger individuals 18-53 suggests that more younger individuals may present initially with 'secondary glioblastoma.'

Influence of obesity-related risk factors in the aetiology of glioma.

BACKGROUND: Obesity and related factors have been implicated as possible aetiological factors for the development of glioma in epidemiological observation studies. We used genetic markers in a Mendelian randomisation framework to examine whether obesity-related traits influence glioma risk. This methodology reduces bias from confounding and is not affected by reverse causation. METHODS: Genetic instruments were identified for 10 key obesity-related risk factors, and their association with glioma risk was evaluated using data from a genome-wide association study of 12,488 glioma patients and 18,169 controls. The estimated odds ratio of glioma associated with each of the genetically defined obesity-related traits was used to infer evidence for a causal relationship. RESULTS: No convincing association with glioma risk was seen for genetic instruments for body mass index, waist-to-hip ratio, lipids, type-2 diabetes, hyperglycaemia or insulin resistance. Similarly, we found no evidence to support a relationship between obesity-related traits with subtypes of glioma-glioblastoma (GBM) or non-GBM tumours. CONCLUSIONS: This study provides no evidence to implicate obesity-related factors as causes of glioma.

Impact of atopy on risk of glioma: a Mendelian randomisation study.

BACKGROUND: An inverse relationship between allergies with glioma risk has been reported in several but not all epidemiological observational studies. We performed an analysis of genetic variants associated with atopy to assess the relationship with glioma risk using Mendelian randomisation (MR), an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations. METHODS: Two-sample MR was undertaken using genome-wide association study data. We used single nucleotide polymorphisms (SNPs) associated with atopic dermatitis, asthma and hay fever, IgE levels, and self-reported allergy as instrumental variables. We calculated MR estimates for the odds ratio (OR) for each risk factor with glioma using SNP-glioma estimates from 12,488 cases and 18,169 controls, using inverse-variance weighting (IVW), maximum likelihood estimation (MLE), weighted median estimate (WME) and mode-based estimate (MBE) methods. Violation of MR assumptions due to directional pleiotropy were sought using MR-Egger regression and HEIDI-outlier analysis. RESULTS: Under IVW, MLE, WME and MBE methods, associations between glioma risk with asthma and hay fever, self-reported allergy and IgE levels were non-significant. An inverse relationship between atopic dermatitis and glioma risk was found by IVW (OR 0.96, 95% confidence interval (CI) 0.93-1.00, P = 0.041) and MLE (OR 0.96, 95% CI 0.94-0.99, P = 0.003), but not by WME (OR 0.96, 95% CI 0.91-1.01, P = 0.114) or MBE (OR 0.97, 95% CI 0.92-1.02, P = 0.194). CONCLUSIONS: Our investigation does not provide strong evidence for relationship between atopy and the risk of developing glioma, but findings do not preclude a small effect in relation to atopic dermatitis. Our analysis also serves to illustrate the value of using several MR methods to derive robust conclusions.

Considerations on the use of the terms radiosensitivity and radiosusceptibility.

The separate use of the terms 'radiosensitivity' and 'radiosusceptibility' has been suggested to describe variability in the risk of, respectively, adverse tissue reactions (deterministic effect) following radiotherapy and radiation-induced cancer (stochastic effect). The aim of this note is to present arguments against such distinction. We feel that it is premature to make a concrete final judgement on these definitions because of the limited understanding of the mechanisms underlying individual sensitivity to both radiation-related cancers and radiation-related tissue injury. Moreover, the exclusive application of 'radiosensitivity' in relation to deterministic effects and the term 'radiosusceptibility' in relation to cancer carries the risk of being wrongly interpreted as evidence for a high, genetically driven sensitivity to radiation in all patients who develop adverse tissue reactions and a high genetic susceptibility to cancer in those who develop radiation-induced malignancies. There is a need for further research to better define these phenomena and their interrelationships.

Common genetic variation and risk of gallbladder cancer in India: a case-control genome-wide association study.

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.

Costs, affordability, and feasibility of an essential package of cancer control interventions in low-income and middle-income countries: key messages from Disease Control Priorities, 3rd edition.

Investments in cancer control--prevention, detection, diagnosis, surgery, other treatment, and palliative care--are increasingly needed in low-income and particularly in middle-income countries, where most of the world's cancer deaths occur without treatment or palliation. To help countries expand locally appropriate services, Cancer (the third volume of nine in Disease Control Priorities, 3rd edition) developed an essential package of potentially cost-effective measures for countries to consider and adapt. Interventions included in the package are: prevention of tobacco-related cancer and virus-related liver and cervical cancers; diagnosis and treatment of early breast cancer, cervical cancer, and selected childhood cancers; and widespread availability of palliative care, including opioids. These interventions would cost an additional US$20 billion per year worldwide, constituting 3% of total public spending on health in low-income and middle-income countries. With implementation of an appropriately tailored package, most countries could substantially reduce suffering and premature death from cancer before 2030, with even greater improvements in later decades.

Occupational Radiation Exposure and Deaths From Malignant Intracranial Neoplasms of the Brain and CNS in U.S. Radiologic Technologists, 1983-2012.

OBJECTIVE: Childhood exposure to acute, high-dose radiation has consistently been associated with risk of benign and malignant intracranial tumors of the brain and CNS, but data on risks of adulthood exposure to protracted, low-to-moderate doses of radiation are limited. In a large cohort of radiologic technologists, we quantified the association between protracted, low-to-moderate doses of radiation and malignant intracranial tumor mortality. MATERIALS AND METHODS: The study population included 83,655 female and 26,642 male U.S. radiologic technologists who were certified for at least 2 years as of 1982. The cohort was followed from the completion date of the first or second survey (1983-1989 or 1994-1998) to the date of death, loss to follow-up, or December 31, 2012, whichever was earliest. Occupational brain doses through 1997 were based on work history, historical data, and, for most years after the mid 1970s, individual film badge measurements. Radiation-related excess relative risks (ERRs) and 95% CIs were estimated from Poisson regression models adjusted for attained age and sex. RESULTS: Cumulative mean absorbed brain dose was 12 mGy (range, 0-290 mGy). During follow-up (median, 26.7 years), 193 technologists died of a malignant intracranial neoplasm. Based on models incorporating a 5-year lagged cumulative brain dose, cumulative brain dose was not associated with malignant intracranial tumor mortality (overall ERR per 100 mGy, 0.1; 95% CI, < -0.3 to 1.5). No effect modification was observed by sex or birth cohort. CONCLUSION: In this nationwide cohort of radiologic technologists, cumulative occupational radiation exposure to the brain was not associated with malignant intracranial tumor mortality.

Relationship between paediatric CT scans and subsequent risk of leukaemia and brain tumours: assessment of the impact of underlying conditions.

BACKGROUND: We previously reported evidence of a dose-response relationship between ionising-radiation exposure from paediatric computed tomography (CT) scans and the risk of leukaemia and brain tumours in a large UK cohort. Underlying unreported conditions could have introduced bias into these findings. METHODS: We collected and reviewed additional clinical information from radiology information systems (RIS) databases, underlying cause of death and pathology reports. We conducted sensitivity analyses excluding participants with cancer-predisposing conditions or previous unreported cancers and compared the dose-response analyses with our original results. RESULTS: We obtained information from the RIS and death certificates for about 40% of the cohort (n∼180 000) and found cancer-predisposing conditions in 4 out of 74 leukaemia/myelodysplastic syndrome (MDS) cases and 13 out of 135 brain tumour cases. As these conditions were unrelated to CT exposure, exclusion of these participants did not alter the dose-response relationships. We found evidence of previous unreported cancers in 2 leukaemia/MDS cases, 7 brain tumour cases and 232 in non-cases. These previous cancers were related to increased number of CTs. Exclusion of these cancers reduced the excess relative risk per mGy by 15% from 0.036 to 0.033 for leukaemia/MDS (P-trend=0.02) and by 30% from 0.023 to 0.016 (P-trend<0.0001) for brain tumours. When we included pathology reports we had additional clinical information for 90% of the cases. Additional exclusions from these reports further reduced the risk estimates, but this sensitivity analysis may have underestimated risks as reports were only available for cases. CONCLUSIONS: Although there was evidence of some bias in our original risk estimates, re-analysis of the cohort with additional clinical data still showed an increased cancer risk after low-dose radiation exposure from CT scans in young patients.

Increased pancreatic cancer risk following radiotherapy for testicular cancer.

BACKGROUND: Pancreatic cancer risk is elevated among testicular cancer (TC) survivors. However, the roles of specific treatments are unclear. METHODS: Among 23 982 5-year TC survivors diagnosed during 1947-1991, doses from radiotherapy to the pancreas were estimated for 80 pancreatic cancer patients and 145 matched controls. Chemotherapy details were recorded. Logistic regression was used to estimate odds ratios (ORs). RESULTS: Cumulative incidence of second primary pancreatic cancer was 1.1% at 30 years after TC diagnosis. Radiotherapy (72 (90%) cases and 115 (80%) controls) was associated with a 2.9-fold (95% confidence interval (CI) 1.0-7.8) increased risk. The OR increased linearly by 0.12 per Gy to the pancreas (P-trend<0.001), with an OR of 4.6 (95% CI 1.9-11.0) for ⩾25 Gy vs <25 Gy. Radiation-related risks remained elevated ⩾20 years after TC diagnosis (P=0.020). The risk increased with the number of cycles of chemotherapy with alkylating or platinum agents (P=0.057), although only one case was exposed to platinum. CONCLUSIONS: A dose-response relationship exists between radiation to the pancreas and subsequent cancer risk, and persists for over 20 years. These excesses, although small, should be considered when radiotherapy with exposure to the pancreas is considered for newly diagnosed patients. Additional data are needed on the role of chemotherapy.

Understanding rural-urban differences in risk factors for breast cancer in an Indian population.

PURPOSE: Although cancer registry data indicate that there are large differences in breast cancer (BC) rates between rural and urban regions of India, the reasons for these differences are not well understood. METHODS: We conducted a hospital based case-control study (1,637 breast cancer cases; 1,515 visitor controls) in Mumbai, India, during the years 2009-2013. Extensive questionnaire data, anthropometry measurement and blood samples were collected on all participants. Using logistic regression models, we estimated risk based on odds ratio (OR) and 95 % confidence intervals (CI) for various reproductive and anthropometric measures, stratified by rural-urban status depending upon residence in first 20 years of life. RESULTS: Waist-to-hip ratio of ≥0.95 compared to ratio ≤0.84 was strongly associated with risk of BC in both rural and urban populations (ORurban = 4.10, 95 % CI 3.03-5.56; ORrural = 3.01, 95 % CI 1.85-4.90). First full-term pregnancy after the age of 25 compared to first full-term pregnancy below 20 years of age was associated with risk of BC in both urban and rural women (ORurban = 1.78, 95 % CI 1.32-2.41; ORrural = 2.24, 95 % CI 1.13-4.43). The prevalence of age at first full-term pregnancy was significantly lower in rural (mean age at first full-term pregnancy = 19.39 years) versus urban women (mean age at first full-term pregnancy = 22.62 years), whereas mean waist circumference was much higher in urban women (82.13 cm) compared to rural women (79.26 cm). We did not observe any association between breast feeding and risk of BC. CONCLUSIONS: Differences in the prevalence of central adiposity and age at first full-term pregnancy between rural and urban women from India may explain some differences in breast cancer rates between these two populations.

Cancer Risks in U.S. Radiologic Technologists Working With Fluoroscopically Guided Interventional Procedures, 1994-2008.

OBJECTIVE: The purpose of this study was to examine risks of cancer incidence and mortality among U.S. radiation technologists performing or assisting with fluoroscopically guided interventional procedures. SUBJECTS AND METHODS: A nationwide prospective cohort of 90,957 radiologic technologists, who responded to a 1994-1998 survey that collected information on whether they had ever worked with fluoroscopically guided interventional procedures, was followed through completion of a subsequent cohort survey during 2003-2005 (for cancer incidence) or December 31, 2008 (for cancer mortality). Sex-adjusted hazard ratios (HRs) and 95% CIs were calculated by use of Cox proportional hazards models for incidence and mortality from all cancers other than nonmelanoma skin cancer and for specific cancer outcomes in participants who reported ever performing fluoroscopically guided interventional procedures compared with technologists who never performed these procedures. RESULTS: The analysis showed an approximately twofold increased risk of brain cancer mortality (HR, 2.55; 95% CI, 1.48-4.40) and modest elevations in incidence of melanoma (HR, 1.30; 95% CI, 1.05-1.61) and in breast cancer incidence (HR, 1.16; 95% CI, 1.02-1.32) but not mortality (HR, 1.07; 95% CI, 0.69-1.66) among technologists who performed fluoroscopically guided interventional procedures compared with those who never performed these procedures. Although there was a small suggestive increase in incidence of all cancers combined, excluding nonmelanoma skin cancers (HR, 1.08; 95% CI, 1.00-1.17), mortality from all cancers combined, excluding nonmelanoma skin cancers, was not elevated (HR, 1.00; 95% CI, 0.88-1.14). We similarly observed no elevated risk of cancers of the thyroid, skin other than melanoma, prostate, lung, or colon and rectum or of leukemia that was not chronic lymphocytic leukemia among workers who performed fluoroscopically guided interventional procedures. CONCLUSION: We observed elevated risks of brain cancer, breast cancer, and melanoma among technologists who performed fluoroscopically guided interventional procedures. Although exposure to low-dose radiation is one possible explanation for these increased risks, these results may also be due to chance or unmeasured confounding by nonradiation risk factors. Our results must be confirmed in other studies, preferably with individual radiation dose data.

Incidence and mortality risks for circulatory diseases in US radiologic technologists who worked with fluoroscopically guided interventional procedures, 1994-2008.

OBJECTIVES: Although fluoroscopically guided interventional procedures (FGIP) have provided major advances in the treatment of various common diseases, radiation exposures associated with these procedures may cause adverse health effects in workers. We assess risk of circulatory disease incidence and mortality in medical radiation workers performing FGIP. METHODS: A US nationwide prospective cohort study of 90,957 radiologic technologists who completed a cohort survey during 1994-1998 was followed until completion of a subsequent survey during 2003-2005 for circulatory disease incidence, or until 31 December 2008 for mortality. Incidence analyses were restricted to the 63,482 technologists who completed both the second survey (1994-1998) and the third survey (2003-2005). Cox proportional hazards models were used to assess adjusted HR and 95% CIs for mortality from all causes, all circulatory diseases, all heart diseases, ischaemic heart disease, stroke, acute myocardial infarction and hypertension in participants who reported ever performing FGIP compared to technologists who never performed FGIP procedures. Adjusted HRs were calculated for self-reported hypertension, stroke and myocardial infarction. RESULTS: We observed a 34% increase in stroke incidence (HR=1.34, 95% CI 1.10 to 1.64) in technologists who performed FGIP compared to those who never performed these procedures. Mortality from stroke was also modestly elevated, although not statistically significant (HR=1.22, 95% CI 0.85 to 1.73). We observed no statistically significant excess risks of incidence or mortality from any other outcome evaluated. CONCLUSIONS: Our finding of elevated risk of stroke in workers performing FGIP needs to be confirmed in studies with individual radiation dose data, but nonetheless underlines the need to keep radiation exposure as low as reasonably achievable without compromising key diagnostic information.

Recommendations for screening and early detection of common cancers in India.

Cancers of the breast, uterine cervix, and lip or oral cavity are three of the most common malignancies in India. Together, they account for about 34% of more than 1 million individuals diagnosed with cancer in India each year. At each of these cancer sites, tumours are detectable at early stages when they are most likely to be cured with standard treatment protocols. Recognising the key role that effective early detection and screening programmes could have in reducing the cancer burden, the Indian Institute for Cytology and Preventive Oncology, in collaboration with the US National Cancer Institute Center for Global Health, held a workshop to summarise feasible options and relevant evidence for screening and early detection of common cancers in India. The evidence-based recommendations provided in this Review are intended to act as a guide for policy makers, clinicians, and public health practitioners who are developing and implementing strategies in cancer control for the three most common cancers in India.

Further Confirmation of Germline Glioma Risk Variant rs78378222 in TP53 and Its Implication in Tumor Tissues via Integrative Analysis of TCGA Data.

We confirmed strong association of rs78378222:A>C (per allele odds ratio [OR] = 3.14; P = 6.48 × 10(-11) ), a germline rare single-nucleotide polymorphism (SNP) in TP53, via imputation of a genome-wide association study of glioma (1,856 cases and 4,955 controls). We subsequently performed integrative analyses on the Cancer Genome Atlas (TCGA) data for GBM (glioblastoma multiforme) and LUAD (lung adenocarcinoma). Based on SNP data, we imputed genotypes for rs78378222 and selected individuals carrying rare risk allele (C). Using RNA sequencing data, we observed aberrant transcripts with ∼3 kb longer than normal for those individuals. Using exome sequencing data, we further showed that loss of haplotype carrying common protective allele (A) occurred somatically in GBM but not in LUAD. Our bioinformatic analysis suggests rare risk allele (C) disrupts mRNA termination, and an allelic loss of a genomic region harboring common protective allele (A) occurs during tumor initiation or progression for glioma.