Impact of blue light therapy on plasma adrenocorticotropic hormone (ACTH) and hypertrichosis in horses with pituitary pars intermedia dysfunction.

Blue light therapy can be used in horses to alter the natural photoperiod and inhibit winter hair coat growth. Seasonal increases in ACTH occur in the fall season but are exaggerated in horses with pituitary pars intermedia dysfunction (PPID). Additionally, PPID horses frequently present with hypertrichosis. Thus, blue light therapy was proposed as a potential management tool for hypertrichosis and for investigating the impact of photoperiod manipulation on ACTH. Eighteen PPID horses, aged 18 to 31 yr, from a university-owned research herd were selected and assigned to either the control group (n = 10) or the treatment (blue light therapy) group (n = 8) based on age and clinical history, which included the results of multiple endocrine tests. Consistent daylength of approximately 14.5 h was maintained for the treated horses from July 15 through approximately late October via the extension of natural daylength using wearable masks that provided short wavelength blue light (465 nm) to 1 eye. The control group was exposed to only the natural photoperiod during this time. All horses were housed on the same farm and remained on pasture for the duration of the study. On Day 0, thyrotropin-releasing hormone (TRH) stimulation tests were performed to confirm PPID status; there were no differences between the 2 groups in resting plasma ACTH or plasma ACTH at 10 min after TRH administration. To determine an effect of treatment on ACTH, blood was collected via jugular venipuncture for measurement of ACTH at sequential timepoints over a 16-h period in mid-October. Hair weights were also assessed throughout the study. No differences in resting plasma ACTH were observed between the 2 groups across the seasonal analysis (July and October) or during the 16-h testing. The PPID horses receiving blue light therapy had lighter hair weights compared to the PPID control horses. These results suggest that blue light therapy does not alter ACTH concentrations but could potentially be used as an additional management tool for hypertrichosis in PPID horses. Manipulation of the photoperiod using blue light therapy did not affect seasonal changes in ACTH in this study.

Effects of pituitary pars intermedia dysfunction and Prascend (pergolide tablets) treatment on endocrine and immune function in horses.

It remains unclear how pituitary pars intermedia dysfunction (PPID) and pergolide treatment (Prascend [pergolide tablets]) affect endocrine and immune function in horses. To evaluate these effects, blood was collected regularly from 28 university-owned horses (10 Non-PPID, 9 PPID control [PC], and 9 PPID treatment [PT]) over approximately 15 mo. Pergolide treatment was initiated after Day 0 collections. Analyses included ACTH, insulin, total cortisol, free cortisol, complete blood counts, plasma myeloperoxidase, and cytokine/receptor gene expression in basal whole blood and in vitro stimulations (PMA/ionomycin, heat-inactivated Rhodococcus equi, and heat-inactivated Escherichia coli) of whole blood and peripheral blood mononuclear cells (PBMCs). The results were analyzed using a linear mixed model (SAS 9.4) with significance set at P < 0.05. Significant group (P = 0.0014) and group-by-time (P = 0.0004) effects were observed in resting ACTH such that PT horses differed from Non-PPID horses only at Day 0. PT horses had significantly lower changes in ACTH responses to thyrotropin-releasing hormone stimulation tests than PC horses at non-fall time points only, mid-late February 2018 (P = 0.016) and early April 2018 (P = 0.0172). When PT and PC horses did not differ, they were combined before comparison to Non-PPID horses. No significant group or group-by-time effects were seen in resting insulin, total cortisol, or free cortisol; however, significant time effects were observed in these measures. PPID horses had lower absolute lymphocyte (P = 0.028) and red blood cell (P = 0.0203) counts than Non-PPID horses. In unstimulated whole blood, PPID horses had increased IL-8 expression compared with Non-PPID horses (P = 0.0102). In addition, PPID horses had decreased interferon γ production from PBMCs after stimulation with R. equi (P = 0.0063) and E. coli (P = 0.0057) and showed increased transforming growth factor ß expression after E. coli stimulation (P = 0.0399). The main limitations of this study were a limited sample size and an inability to truly randomize the PPID horses into treatment groups. Resting ACTH is likely the best choice for determining successful responses to pergolide. Neither PPID nor pergolide appears to influence insulin, total cortisol, and free cortisol. As measured, systemic immune function was altered in PPID horses, and it is likely that these horses are indeed at increased risk of opportunistic infection. Despite reducing ACTH, pergolide treatment did not appear to influence immune function.

The role of screening mammography in the era of modern breast cancer treatment.

The evidence is reviewed on the efficacy and effectiveness of mammography screening derived from randomized screening trials and from the surveillance of populations where mammography screening for breast cancer has been introduced. Nearly all the trials were performed in the era before modern adjuvant therapy for breast cancer was introduced, apart from the Canadian National Breast Screening Study and the UK Age trial. The former found no benefit from annual mammography screening for 5 years in women age 40-59 years, the latter, a non-significant benefit from screening women by annual mammography for 7 years from ages 39 to 41 years. The evidence from population-based surveillance is mixed, most such studies having failed to consider the benefit gained from improved therapy. It is concluded that we have reached the point of negligible benefit from mammography screening for breast cancer in women at average risk, and that we should concentrate on early diagnosis of breast cancer and the application of modern therapy according to clearly defined sub-types of breast cancer.

The OncoSim model: development and use for better decision-making in Canadian cancer control.

The Canadian Partnership Against Cancer was created in 2007 by the federal government to accelerate cancer control across Canada. Its OncoSim microsimulation model platform, which consists of a suite of specific cancer models, was conceived as a tool to augment conventional resources for population-level policy- and decision-making. The Canadian Partnership Against Cancer manages the OncoSim program, with funding from Health Canada and model development by Statistics Canada. Microsimulation modelling allows for the detailed capture of population heterogeneity and health and demographic history over time. Extensive data from multiple Canadian sources were used as inputs or to validate the model. OncoSim has been validated through expert consultation; assessments of face validity, internal validity, and external validity; and model fit against observed data. The platform comprises three in-depth cancer models (lung, colorectal, cervical), with another in-depth model (breast) and a generalized model (25 cancers) being in development. Unique among models of its class, OncoSim is available online for public sector use free of charge. Users can customize input values and output display, and extensive user support is provided. OncoSim has been used to support decision-making at the national and jurisdictional levels. Although simulation studies are generally not included in hierarchies of evidence, they are integral to informing cancer control policy when clinical studies are not feasible. OncoSim can evaluate complex intervention scenarios for multiple cancers. Canadian decision-makers thus have a powerful tool to assess the costs, benefits, cost-effectiveness, and budgetary effects of cancer control interventions when faced with difficult choices for improvements in population health and resource allocation.

Implementing low-dose computed tomography screening for lung cancer in Canada: implications of alternative at-risk populations, screening frequency, and duration.

BACKGROUND: Low-dose computed tomography (ldct) screening has been shown to reduce mortality from lung cancer; however, the optimal screening duration and "at risk" population are not known. METHODS: The Cancer Risk Management Model developed by Statistics Canada for the Canadian Partnership Against Cancer includes a lung screening module based on data from the U.S. National Lung Screening Trial (nlst). The base-case scenario reproduces nlst outcomes with high fidelity. The impact in Canada of annual screening on the number of incident cases and life-years gained, with a wider range of age and smoking history eligibility criteria and varied participation rates, was modelled to show the magnitude of clinical benefit nationally and by province. Life-years gained, costs (discounted and undiscounted), and resource requirements were also estimated. RESULTS: In 2014, 1.4 million Canadians were eligible for screening according to nlst criteria. Over 10 years, screening would detect 12,500 more lung cancers than the expected 268,300 and would gain 9200 life-years. The computed tomography imaging requirement of 24,000-30,000 at program initiation would rise to between 87,000 and 113,000 by the 5th year of an annual nlst-like screening program. Costs would increase from approximately $75 million to $128 million at 10 years, and the cumulative cost nationally over 10 years would approach $1 billion, partially offset by a reduction in the costs of managing advanced lung cancer. CONCLUSIONS: Modelling various ways in which ldct might be implemented provides decision-makers with estimates of the effect on clinical benefit and on resource needs that clinical trial results are unable to provide.

Using the Cancer Risk Management Model to evaluate the health and economic impacts of cytology compared with human papillomavirus DNA testing for primary cervical cancer screening in Canada.

BACKGROUND: In Canada, discussion about changing from cytology to human papillomavirus (hpv) dna testing for primary screening in cervical cancer is ongoing. However, the Canadian Task Force on Preventive Health Care has not yet made a recommendation, concluding that the evidence is insufficient. METHODS: We used the cervical cancer and hpv transmission models of the Cancer Risk Management Model to study the health and economic outcomes of primary cytology compared with hpv dna testing in 14 screening scenarios with varying screening modalities and intervals. Projected cervical cancer cases, deaths, colposcopies, screens, costs, and incremental cost-effectiveness were evaluated. We performed sensitivity analyses for hpv dna test costs. RESULTS: Compared with triennial cytology from age 25, 5-yearly hpv dna screening alone from age 30 resulted in equivalent incident cases and deaths, but 55% (82,000) fewer colposcopies and 43% (1,195,000) fewer screens. At hpv dna screening intervals of 3 years, whether alone or in an age-based sequence with cytology, screening costs are greater, but at intervals of more than 5 years, they are lower. Scenarios on the cost-effectiveness frontier were hpv dna testing alone every 10, 7.5, 5, or 3 years, and triennial cytology starting at age 21 or 25 when combined with hpv dna testing every 3 years. CONCLUSIONS: Changing from cytology to hpv dna testing as the primary screening test for cervical cancer would be an acceptable strategy in Canada with respect to incidence, mortality, screening and diagnostic test volumes.

Cost-effectiveness of breast cancer screening policies using simulation.

In this paper, we study breast cancer screening policies using computer simulation. We developed a multi-state Markov model for breast cancer progression, considering both the screening and treatment stages of breast cancer. The parameters of our model were estimated through data from the Canadian National Breast Cancer Screening Study as well as data in the relevant literature. Using computer simulation, we evaluated various screening policies to study the impact of mammography screening for age-based subpopulations in Canada. We also performed sensitivity analysis to examine the impact of certain parameters on number of deaths and total costs. The analysis comparing screening policies reveals that a policy in which women belonging to the 40-49 age group are not screened, whereas those belonging to the 50-59 and 60-69 age groups are screened once every 5 years, outperforms others with respect to cost per life saved. Our analysis also indicates that increasing the screening frequencies for the 50-59 and 60-69 age groups decrease mortality, and that the average number of deaths generally decreases with an increase in screening frequency. We found that screening annually for all age groups is associated with the highest costs per life saved. Our analysis thus reveals that cost per life saved increases with an increase in screening frequency.

Status Report--Retracing the history of the early development of national chronic disease surveillance in Canada and the major role of the Laboratory Centre for Disease Control (LCDC) from 1972 to 2000.

TITRE: Rapport d'étape - Historique des débuts de la surveillance nationale des maladies chroniques au Canada et rôle majeur du Laboratoire de lutte contre la maladie (LLCM) de 1972 à 2000. INTRODUCTION: La surveillance de la santé consiste en l'utilisation systématique et continue de données sur la santé recueillies régulièrement en vue d'orienter les mesures de santé publique en temps opportun. Ce document décrit la création et l'essor des systèmes nationaux de surveillance au Canada et les répercussions de ces systèmes sur la prévention des maladies chroniques et des blessures. En 2008, les auteurs ont commencé à retracer l'historique des débuts de la surveillance nationale des maladies chroniques au Canada, en commençant à 1960, et ils ont poursuivi leur examen jusqu'en 2000. Une publication de 1967 a retracé l'historique de la création du Laboratoire d'hygiène de 1921 à 1967. Notre étude fait suite à cette publication et décrit l'historique de l'établissement de la surveillance nationale des maladies chroniques au Canada, à la fois avant et après la création du Laboratoire de lutte contre la maladie (LCDC).

Using the Cancer Risk Management Model to evaluate colorectal cancer screening options for Canada.

BACKGROUND: Several screening methods for colorectal cancer (crc) are available, and some have been shown by randomized trials to be effective. In the present study, we used a well-developed population health simulation model to compare the risks and benefits of a variety of screening scenarios. Tests considered were the fecal occult blood test (fobt), the fecal immunochemical test (fit), flexible sigmoidoscopy, and colonoscopy. Outcomes considered included years of life gained, crc cases and deaths prevented, and direct health system costs. METHODS: A natural history model of crc was implemented and calibrated to specified targets within the framework of the Cancer Risk Management Model (crmm) from the Canadian Partnership Against Cancer. The crmm-crc permits users to enter their own parameter values or to use program-specified base values. For each of 23 screening scenarios, we used the crmm-crc to run 10 million replicate simulations. RESULTS: Using base parameter values and some user-specified values in the crmm-crc, and comparing our screening scenarios with no screening, all screening scenarios were found to reduce the incidence of and mortality from crc. The fobt was the least effective test; it was not associated with lower net cost. Colonoscopy screening was the most effective test; it had net costs comparable to those for several other strategies considered, but required more than 3 times the colonoscopy resources needed by other approaches. After colonoscopy, strategies based on the fit were predicted to be the most effective. In sensitivity analyses performed for the fobt and fit screening strategies, fobt parameter values associated with high-sensitivity formulations were associated with a substantial increase in test effectiveness. The fit was more cost-effective at the 50 ng/mL threshold than at the 100 ng/mL threshold. CONCLUSIONS: The crmm-crc provides a sophisticated and flexible environment in which to evaluate crc control options. All screening scenarios considered in this study effectively reduced crc mortality, although sensitivity analyses demonstrated some uncertainty in the magnitude of the improvements. Where possible, local data should be used to reduce uncertainty in the parameters.

Impact of screening mammography on mortality from breast cancer before age 60 in women 40 to 49 years of age.

BACKGROUND: Whether screening mammography programs should include women in their 40s is controversial. In Canada, screening of women aged 40-49 years has not been shown to reduce mortality from breast cancer. Given that screening mammography reduces mean tumour size and that tumour size is inversely associated with survival, the lack of benefit seen with screening is puzzling and suggests a possible adverse effect on mortality of mammography or subsequent treatment (or both) that counterbalances the expected benefit derived from downstaging. METHODS: We followed 50,436 women 40-49 years of age until age 60 for mortality from breast cancer. Of those women, one half had been randomly assigned to annual mammography and one half to no mammography. The impact of mammography on breast cancer mortality was estimated using a left-censored Cox proportional hazards model. RESULTS: Of 256 deaths from breast cancer recorded in the study cohort, 134 occurred in women allocated to mammography, and 122 occurred in those receiving usual care and not allocated to mammography. The cumulative risk of death from breast cancer to age 60 was 0.53% for women assigned to mammography and 0.48% for women not so assigned. The hazard ratio for breast cancer-specific death associated with 1 or more screening mammograms before age 50 was 1.10 (95% confidence interval: 0.86 to 1.40). CONCLUSIONS: Mammography in women 40-49 years of age is associated with a small but nonsignificant increase in the risk of dying of breast cancer before age 60. Caution should be exercised when recommending mammographic screening to women before age 50.

Diabetes, antidiabetic medications, and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium.

BACKGROUND: Type 2 diabetes mellitus has been associated with an excess risk of pancreatic cancer, but the magnitude of the risk and the time-risk relationship are unclear, and there is limited information on the role of antidiabetic medications. PATIENTS AND METHODS: We analyzed individual-level data from 15 case-control studies within the Pancreatic Cancer Case-Control Consortium, including 8305 cases and 13 987 controls. Pooled odds ratios (ORs) were estimated from multiple logistic regression models, adjusted for relevant covariates. RESULTS: Overall, 1155 (15%) cases and 1087 (8%) controls reported a diagnosis of diabetes 2 or more years before cancer diagnosis (or interview, for controls), corresponding to an OR of 1.90 (95% confidence interval, CI, 1.72-2.09). Consistent risk estimates were observed across strata of selected covariates, including body mass index and tobacco smoking. Pancreatic cancer risk decreased with duration of diabetes, but a significant excess risk was still evident 20 or more years after diabetes diagnosis (OR 1.30, 95% CI 1.03-1.63). Among diabetics, long duration of oral antidiabetic use was associated with a decreased pancreatic cancer risk (OR 0.31, 95% CI 0.14-0.69, for ≥15 years). Conversely, insulin use was associated with a pancreatic cancer risk in the short term (OR 5.60, 95% CI 3.75-8.35, for <5 years), but not for longer duration of use (OR 0.95, 95% CI 0.53-1.70, for ≥15 years). CONCLUSION: This study provides the most definitive quantification to date of an excess risk of pancreatic cancer among diabetics. It also shows that a 30% excess risk persists for more than two decades after diabetes diagnosis, thus supporting a causal role of diabetes in pancreatic cancer. Oral antidiabetics may decrease the risk of pancreatic cancer, whereas insulin showed an inconsistent duration-risk relationship.

Dairy products and pancreatic cancer risk: a pooled analysis of 14 cohort studies.

Pancreatic cancer has few early symptoms, is usually diagnosed at late stages, and has a high case-fatality rate. Identifying modifiable risk factors is crucial to reducing pancreatic cancer morbidity and mortality. Prior studies have suggested that specific foods and nutrients, such as dairy products and constituents, may play a role in pancreatic carcinogenesis. In this pooled analysis of the primary data from 14 prospective cohort studies, 2212 incident pancreatic cancer cases were identified during follow-up among 862 680 individuals. Adjusting for smoking habits, personal history of diabetes, alcohol intake, body mass index (BMI), and energy intake, multivariable study-specific hazard ratios (MVHR) and 95% confidence intervals (CIs) were calculated using the Cox proportional hazards models and then pooled using a random effects model. There was no association between total milk intake and pancreatic cancer risk (MVHR = 0.98, 95% CI = 0.82-1.18 comparing ≥500 with 1-69.9 g/day). Similarly, intakes of low-fat milk, whole milk, cheese, cottage cheese, yogurt, and ice-cream were not associated with pancreatic cancer risk. No statistically significant association was observed between dietary (MVHR = 0.96, 95% CI = 0.77-1.19) and total calcium (MVHR = 0.89, 95% CI = 0.71-1.12) intake and pancreatic cancer risk overall when comparing intakes ≥1300 with <500 mg/day. In addition, null associations were observed for dietary and total vitamin D intake and pancreatic cancer risk. Findings were consistent within sex, smoking status, and BMI strata or when the case definition was limited to pancreatic adenocarcinoma. Overall, these findings do not support the hypothesis that consumption of dairy foods, calcium, or vitamin D during adulthood is associated with pancreatic cancer risk.

Ulcer, gastric surgery and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium (PanC4).

BACKGROUND: Peptic ulcer and its treatments have been associated to pancreatic cancer risk, although the evidence is inconsistent. METHODS: We pooled 10 case-control studies within the Pancreatic Cancer Case-control Consortium (PanC4), including 4717 pancreatic cancer cases and 9374 controls, and estimated summary odds ratios (OR) using multivariable logistic regression models. RESULTS: The OR for pancreatic cancer was 1.10 [95% confidence interval (CI) 0.98-1.23] for history of ulcer (OR = 1.08 for gastric and 0.97 for duodenal ulcer). The association was stronger for a diagnosis within 2 years before cancer diagnosis (OR = 2.43 for peptic, 1.75 for gastric, and 1.98 for duodenal ulcer). The OR was 1.53 (95% CI 1.15-2.03) for history of gastrectomy; however, the excess risk was limited to a gastrectomy within 2 years before cancer diagnosis (OR = 6.18, 95% CI 1.82-20.96), while no significant increased risk was observed for longer time since gastrectomy. No associations were observed for pharmacological treatments for ulcer, such as antacids, H2-receptor antagonists, or proton-pump inhibitors. CONCLUSIONS: This uniquely large collaborative study does not support the hypothesis that peptic ulcer and its treatment materially affect pancreatic cancer risk. The increased risk for short-term history of ulcer and gastrectomy suggests that any such association is due to increased cancer surveillance.

Parameter estimates for invasive breast cancer progression in the Canadian National Breast Screening Study.

BACKGROUND: The aim of screening is to detect a cancer in the preclinical state. However, a false-positive or a false-negative test result is a real possibility. METHODS: We describe invasive breast cancer progression in the Canadian National Breast Screening Study and construct progression models with and without covariates. The effect of risk factors on transition intensities and false-negative probability is investigated. We estimate the transition rates, the sojourn time and sensitivity of diagnostic tests for women aged 40-49 and 50-59. RESULTS: Although younger women have a slower transition rate from healthy state to preclinical, their screen-detected tumour becomes evident sooner. Women aged 50-59 have a higher mortality rate compared with younger women. The mean sojourn times for women aged 40-49 and 50-59 are 2.5 years (95% CI: 1.7, 3.8) and 3.0 years (95% CI: 2.1, 4.3), respectively. Sensitivity of diagnostic procedures for older women is estimated to be 0.75 (95% CI: 0.55, 0.88), while women aged 40-49 have a lower sensitivity (0.61, 95% CI: 0.42, 0.77). Age is the only factor that affects the false-negative probability. For women aged 40-49, 'age at entry', 'history of breast disease' and 'families with breast cancer' are found to be significant for some of the transition rates. For the age-group 50-59, 'age at entry', 'history of breast disease', 'menstruation length' and 'number of live births' are found to affect the transition rates. CONCLUSION: Modelling and estimating the parameters of cancer progression are essential steps towards evaluating the effectiveness of screening policies. The parameters include the transition rates, the preclinical sojourn time, the sensitivity, and the effect of different risk factors on cancer progression.

The etiology of uterine sarcomas: a pooled analysis of the epidemiology of endometrial cancer consortium.

BACKGROUND: Uterine sarcomas are characterised by early age at diagnosis, poor prognosis, and higher incidence among Black compared with White women, but their aetiology is poorly understood. Therefore, we performed a pooled analysis of data collected in the Epidemiology of Endometrial Cancer Consortium. We also examined risk factor associations for malignant mixed mullerian tumours (MMMTs) and endometrioid endometrial carcinomas (EECs) for comparison purposes. METHODS: We pooled data on 229 uterine sarcomas, 244 MMMTs, 7623 EEC cases, and 28,829 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) for risk factors associated with uterine sarcoma, MMMT, and EEC were estimated with polytomous logistic regression. We also examined associations between epidemiological factors and histological subtypes of uterine sarcoma. RESULTS: Significant risk factors for uterine sarcoma included obesity (body mass index (BMI)≥30 vs BMI<25 kg m(-2) (OR: 1.73, 95% CI: 1.22-2.46), P-trend=0.008) and history of diabetes (OR: 2.33, 95% CI: 1.41-3.83). Older age at menarche was inversely associated with uterine sarcoma risk (≥15 years vs <11 years (OR: 0.70, 95% CI: 0.34-1.44), P-trend: 0.04). BMI was significantly, but less strongly related to uterine sarcomas compared with EECs (OR: 3.03, 95% CI: 2.82-3.26) or MMMTs (OR: 2.25, 95% CI: 1.60-3.15, P-heterogeneity=0.01). CONCLUSION: In the largest aetiological study of uterine sarcomas, associations between menstrual, hormonal, and anthropometric risk factors and uterine sarcoma were similar to those identified for EEC. Further exploration of factors that might explain patterns of age- and race-specific incidence rates for uterine sarcoma are needed.

Cigarette smoking and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (Panc4).

BACKGROUND: To evaluate the dose-response relationship between cigarette smoking and pancreatic cancer and to examine the effects of temporal variables. METHODS: We analyzed data from 12 case-control studies within the International Pancreatic Cancer Case-Control Consortium (PanC4), including 6507 pancreatic cases and 12 890 controls. We estimated summary odds ratios (ORs) by pooling study-specific ORs using random-effects models. RESULTS: Compared with never smokers, the OR was 1.2 (95% confidence interval [CI] 1.0-1.3) for former smokers and 2.2 (95% CI 1.7-2.8) for current cigarette smokers, with a significant increasing trend in risk with increasing number of cigarettes among current smokers (OR=3.4 for ≥35 cigarettes per day, P for trend<0.0001). Risk increased in relation to duration of cigarette smoking up to 40 years of smoking (OR=2.4). No trend in risk was observed for age at starting cigarette smoking, whereas risk decreased with increasing time since cigarette cessation, the OR being 0.98 after 20 years. CONCLUSIONS: This uniquely large pooled analysis confirms that current cigarette smoking is associated with a twofold increased risk of pancreatic cancer and that the risk increases with the number of cigarettes smoked and duration of smoking. Risk of pancreatic cancer reaches the level of never smokers ∼20 years after quitting.

Alcohol consumption and pancreatic cancer: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4).

BACKGROUND: Heavy alcohol drinking has been related to pancreatic cancer, but the issue is still unsolved. METHODS: To evaluate the role of alcohol consumption in relation to pancreatic cancer, we conducted a pooled analysis of 10 case-control studies (5585 cases and 11,827 controls) participating in the International Pancreatic Cancer Case-Control Consortium. We computed pooled odds ratios (ORs) by estimating study-specific ORs adjusted for selected covariates and pooling them using random effects models. RESULTS: Compared with abstainers and occasional drinkers (< 1 drink per day), we observed no association for light-to-moderate alcohol consumption (≤ 4 drinks per day) and pancreatic cancer risk; however, associations were above unity for higher consumption levels (OR = 1.6, 95% confidence interval 1.2-2.2 for subjects drinking ≥ 9 drinks per day). Results did not change substantially when we evaluated associations by tobacco smoking status, or when we excluded participants who reported a history of pancreatitis, or participants whose data were based upon proxy responses. Further, no notable differences in pooled risk estimates emerged across strata of sex, age, race, study type, and study area. CONCLUSION: This collaborative-pooled analysis provides additional evidence for a positive association between heavy alcohol consumption and the risk of pancreatic cancer.

Cigar and pipe smoking, smokeless tobacco use and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (PanC4).

BACKGROUND: Cigarette smoking is the best-characterized risk factor for pancreatic cancer. However, data are limited for other tobacco smoking products and smokeless tobacco. MATERIALS AND METHODS: We conducted a pooled analysis of cigar and pipe smoking and smokeless tobacco use and risk of pancreatic cancer using data from 11 case-control studies (6056 cases and 11,338 controls) within the International Pancreatic Cancer Case-Control Consortium (PanC4). Pooled odds ratios (OR) and the corresponding 95% confidence intervals (CI) were estimated by unconditional multiple logistic regression models adjusted for study center and selected covariates. RESULTS: Compared with never tobacco users, the OR for cigar-only smokers was 1.6 (95% CI: 1.2-2.3), i.e. comparable to that of cigarette-only smokers (OR 1.5; 95% CI 1.4-1.6). The OR was 1.1 (95% CI 0.69-1.6) for pipe-only smokers. There was some evidence of increasing risk with increasing amount of cigar smoked per day (OR 1.82 for ≥ 10 grams of tobacco), although not with duration. The OR for ever smokeless tobacco users as compared with never tobacco users was 0.98 (95% CI 0.75-1.3). CONCLUSION: This collaborative analysis provides evidence that cigar smoking is associated with an excess risk of pancreatic cancer, while no significant association emerged for pipe smoking and smokeless tobacco use.