Estimating the current and future cancer burden in Canada: Methodological framework of the Canadian population attributable risk of cancer (ComPARe) study

Introduction The Canadian Population Attributable Risk of Cancer project aims to quantify the number and proportion of cancer cases incident in Canada, now and projected to 2042, that could be prevented through changes in the prevalence of modifiable exposures associated with cancer. The broad risk factor categories of interest include tobacco, diet, energy imbalance, infectious diseases, hormonal therapies and environmental factors such as air pollution and res

Estimates of the future burden of cancer attributable to infections in Canada

More than 7000 incident cancers diagnosed in Canada in 2015 were attributable to infections. The future infection-associated cancer burden can be lowered by reducing the prevalence of major cancer-causing infections; hepatitis B virus (HBV), hepatitis C virus (HCV), Helicobacter pylori (H. pylori) and human papillomavirus (HPV). We modeled the future impact of (1) 10%, 25%, and 50% relative reductions in the prevalence of HBV, HCV and H. pylori and (2) different school-based HPV vaccination coverage levels (lower, current, higher) on Canadian cancer incidence by the year 2042. We modeled counterfactual reductions in HBV, HCV and H. pylori prevalence in 2018, assuming a latenc

Genital immunization of heifers with a glycoprotein Edeleted, recombinant bovine herpesvirus 1 strain confers protection upon challenge with a virulent isolate Imunização genital de bezerras com uma cepa recombinante do herpesvírus bovino tipo 1 defectiva na glicoproteína E confere proteção frente a desafio com um isolado virulento

Venereal infection of seronegative heifers and cows with bovine herpesvirus type 1.2 (BoHV-1.2) frequently results in vulvovaginitis and transient infertility. Parenteral immunization with inactivated or modified live BoHV-1 vaccines often fails in conferring protection upon genital challenge. We herein report an evaluation of the immune response and protection conferred by genital vaccination of heifers with a glycoprotein E-deleted recombinant virus (SV265gE-). A group of six seronegative heifers was vaccinated with SV265gE- (0,2mL containing 10(6.9)TCID50) in the vulva submucosa (group IV); four heifers were vaccinated intramuscularly (group IM, 1mL containing 10(7.6)TCID50) and four heifers remained as non-vaccinated controls. Heifers vaccinated IV developed mild, transient local edema and hyperemia and shed low amounts of virus for a few days after vaccination, yet a sentinel heifer maintained in close contact did not seroconvert. Attempts to reactivate the vaccine virus in two IV vaccinated heifers by intravenous administration of dexamethasone (0.5mg/kg) at day 70 pv failed since no virus shedding, recrudescence of genital signs or seroconversion were observed. At day 70 pv, all vaccinated and control heifers were challenged by genital inoculation of a highly virulent BoHV-1.2 isolate (SV56/90, 10(7.1)TCID50/animal). After challenge, virus shedding was detected in genital secretions of control animals for 8.2 days (8-9); in the IM group for 6.2 days (4-8 days) and during 5.2 days (5-6 days) in the IV group. Control non-vaccinated heifers developed moderate (2/4) or severe (2/4) vulvovaginitis lasting 9 to 13 days (x: 10.7 days). The disease was characterized by vulvar edema, vulvo-vestibular congestion, vesicles progressing to coalescence and erosions, fibrino-necrotic plaques and fibrinopurulent exudate. IM vaccinated heifers developed mild (1/3) or moderate (3/4) genital lesions, lasting 10 to 12 days (x: 10.7 days); and IV vaccinated heifers developed mild and transient vulvovaginitis (3/4) or mild to moderate genital lesions (1/4). In the IV group, the clinical signs lasted 4 to 8 days (x: 5.5 days). Clinical examination of the animals after challenge revealed that vaccination by both routes conferred some degree of protection, yet IV vaccination was clearly more effective in reducing the severity and duration of clinical disease. Furthermore, IV vaccination reduced the period of virus shedding in comparison with both groups. Taken together, these results demonstrate that SV265gE- is sufficiently attenuated upon IV vaccination in a low-titer dosis, is not readily reactivated after corticosteroid treatment and lastly, and more importantly, confers local protection upon challenge with a high titer of a virulent heterologous BoHV-1 isolate. Therefore, the use of this recombinant for genital immunization may be considered for prevention of BoHV-1-associated genital disease in the field.<br>A infecção genital de novilhas ou vacas soronegativas pelo herpesvírus bovino tipo 1.2 (BoHV-1.2) pode resultar em vulvovaginite e infertilidade temporária. As vacinas atenuadas ou inativadas administradas pela via parenteral freqüentemente conferem proteção incompleta frente a desafio pela via genital. Este estudo relata uma avaliação da resposta imunológica e proteção conferida pela vacinação genital de bezerras soronegativas com uma cepa recombinante do BoHV-1 defectiva na glicoproteína E (SV265gE-). Um grupo de seis bezerras foi vacinado com a cepa SV265gE(0,2mL contendo 10(6,9)TCID50) na submucosa da vulva (grupo IV); quatro bezerras foram vacinadas pela via intramuscular (IM; dose 10(7,6)TCID50) e quatro bezerras permaneceram como controles não-vacinadas. As bezerras vacinadas pela via IV apresentaram edema e hiperemia leve e transitório na vulva e excretaram vírus em títulos baixos por alguns dias após a vacinação, porém uma bezerra soronegativa mantida em contato não soroconverteu. Administração de dexametasona pela via intravenosa no dia 70pv (0,5mg/kg) em duas bezerras vacinadas pela via IV não resultou em excreção viral, recrudescência clínica ou soroconversão. No dia 70pv, as bezerras vacinadas e as controle foram desafiadas pela inoculação genital da cepa de BoHV-1.2 altamente virulenta SV56/90 (10(7.1)TCID50/animal). Após o desafio, excreção viral nas secreções genitais das bezerras controle foi detectada por 8,2 dias (8-9); no grupo IM durante 6,2 dias (4-8 dias) e durante 5,2 dias (5-6) nas bezerras do grupo IN. As bezerras do grupo controle desenvolveram vulvovaginite moderada (2/4) a severa (2/4) que duraram entre 9 e 13 dias (x: 10,7 dias). A doença se caracterizou por edema vulvar, congestão vulvo-vestibular, formação de vesículas/pústulas que coalesceram, erosões, placas fibrino-necróticas e exsudato fibrino-purulento. As bezerras do grupo IM desenvolveram lesões genitais leves (1/3) a moderadas (3/4), com duração de 10 a 12 dias (x: 10,7 dias). No grupo IV, as bezerras desenvolveram vulvovaginite leve e transitória (3/4) ou lesões moderadas (1/4), com duração de 4 a 8 dias (x: 5,5 dias). O exame clínico desses animais após o desafio demonstrou que a vacinação, independentemente da via de administração, conferiu proteção e que, a vacinação IV mostrou-se mais efetiva na redução da severidade e duração da doença clínica. A vacinação IV também determinou uma redução significativa no período de excreção viral após desafio, em comparação com os grupos controle e IM. Esses resultados demonstram que a cepa SV265gE- administrada pela via IV confere proteção satisfatória frente a desafio local com um isolado heterólogo de BoHV-1 altamente virulento. Além disso, a cepa vacinal é atenuada para vacinação IV em baixos títulos e não é reativada facilmente após administração de dexametasona. Assim, a utilização da cepa recombinante para imunização genital pode se constituir em alternativa para prevenir a infecção e doença reprodutiva associada com o BoHV-1

The current and future burden of cancer attributable to red and processed meat consumption in Canada

Red meat and processed meat have been consistently associated with an increased risk of colorectal, stomach, pancreatic cancer and esophageal cancer (processed meat only). The purpose of this analysis was to estimate the current attributable and future avoidable burden of cancer related to red and processed meat consumption in Canada. We estimated the population attributable risk of cancer separately for red meat consumption (beef, lamb, and pork, excluding processed meat) and processed meat consumption (sausage and bacon) incorporating current cancer incidence data, relative risks, and exposure prevalence. We also estimated the future avoidable burden of cancer from 2015 to 2042 for Canada and by province using the potential impact fraction associated with various potential intervention scenarios intended to reduce consumption, ranging from a decrease of 0.2 servings/week to 2.0 servings/week among the adult Canadian population aged 20 and over. The estimated mean red meat consumption in the Canadian population in 2007 to 2011 was approximately 3.2 times per week. In addition, Canadians consume an average of 1.2 times of processed meat per week. In 2015, an estimated 5.9% of associated cancers and 0.9% of all cancers were attributable to red meat consumption. An estimated 4.5% of associated cancers and 0.7% of all cancers were attributable to processed meat consumption. A mean decrease of 0.5 servings/week of red meat or processed meat could prevent about 8700 or 16,600 cancer cases, respectively, between 2015 and 2042. In conclusion, a small but meaningful cancer burden is associated with red and processed meat consumption. Interventions aimed at reducing consumption at the population level have the potential in the prevention of many cancers in Canada

Estimates of the current and future burden of lung cancer attributable to residential radon exposure in Canada

Radon is widely recognized as a human carcinogen and findings from epidemiologic studies support a causal association between residential radon exposure and lung cancer risk. Our aim was to derive population attributable risks (PAR) to estimate the numbers of incident lung cancer due to residential radon exposure in Canada in 2015. Potential impact fractions for 2042 were estimated based on a series of counterfactuals. A meta-analysis was conducted to estimate the relative risk of lung cancer per 100 Becquerels (Bq)/m 3 increase in residential radon exposure, with a pooled estimate of 1.16 (95% CI: 1.07–1.24). The population distribution of annual residential radon exposure was estimated based on a national survey with adjustment for changes in the population distribution over time, the proportion of Canadians living in high-rise buildings, and to reflect annual rather than winter levels. An estimated 6.9% of lung cancer cases in 2015 were attributable to exposure to residential radon, accounting for 1741 attributable cases. If mitigation efforts were to reduce all residential radon exposures that are above current Canadian policy guidelines of 200 Bq/m 3 (3% of Canadians) to 50 Bq/m 3 , 293 cases could be prevented in 2042, and 2322 cumulative cases could be prevented between 2016 and 2042. Our results show that mitigation that exclusively targets Canadian homes with radon exposures above current Canadian guidelines may not greatly alleviate the future projected lung cancer burden. Mitigation of residential radon levels below current guidelines may be required to substantially reduce the overall lung cancer burden in the Canadian population