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1.
J Infect Dis ; 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31504649

RESUMO

BACKGROUND: To understand real-world HPV vaccine impact, continuous evaluation using population-based data is critical. We evaluated the early impact of the school-based HPV immunization program on cervical dysplasia in females in British Columbia (BC), Canada. METHODS: Data linkage was performed using records from the provincial cervical screening and immunization registries. Precancerous outcomes were compared between unvaccinated and HPV vaccinated females born in 1994-2005. Incidence rate (IR) and relative rate (RR) and vaccine effectiveness (VE), using unadjusted and adjusted Poisson regression, of cytology (HSIL) and histopathology (CIN2, CIN3 and CIN2+) outcomes were compared across vaccination status groups. RESULTS: Females who received a complete series of vaccine on schedule between the ages of 9-14 had a adjusted RR=0.42 (95%CI 0.31 - 0.57) for CIN2+ over 7 years of follow-up compared to unvaccinated females, resulting in a VE of 57.9% (95%CI 43.2-69.0%). The adjusted RR for HSIL was 0.53 (95%CI 0.43-0.64), resulting in a VE of 47.1% (95%CI 35.6-56.7%). CONCLUSION: Females vaccinated against HPV have a lower incidence of cervical dysplasia compared to unvaccinated females. Immunization between 9 - 14 years of age should be encouraged. Continued program evaluation is important for measuring long-term population impact.

2.
Genet Epidemiol ; 43(7): 844-863, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31407831

RESUMO

Epidemiologic studies show an increased risk of non-Hodgkin lymphoma (NHL) in patients with autoimmune disease (AD), due to a combination of shared environmental factors and/or genetic factors, or a causative cascade: chronic inflammation/antigen-stimulation in one disease leads to another. Here we assess shared genetic risk in genome-wide-association-studies (GWAS). Secondary analysis of GWAS of NHL subtypes (chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and marginal zone lymphoma) and ADs (rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis). Shared genetic risk was assessed by (a) description of regional genetic of overlap, (b) polygenic risk score (PRS), (c)"diseasome", (d)meta-analysis. Descriptive analysis revealed few shared genetic factors between each AD and each NHL subtype. The PRS of ADs were not increased in NHL patients (nor vice versa). In the diseasome, NHLs shared more genetic etiology with ADs than solid cancers (p = .0041). A meta-analysis (combing AD with NHL) implicated genes of apoptosis and telomere length. This GWAS-based analysis four NHL subtypes and three ADs revealed few weakly-associated shared loci, explaining little total risk. This suggests common genetic variation, as assessed by GWAS in these sample sizes, may not be the primary explanation for the link between these ADs and NHLs.

3.
Cancer Causes Control ; 30(8): 889-900, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31165419

RESUMO

PURPOSE: To conduct a pooled analysis assessing the association of blood transfusion with risk of non-Hodgkin lymphoma (NHL). METHODS: We used harmonized data from 13 case-control studies (10,805 cases, 14,026 controls) in the InterLymph Consortium. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression, adjusted for study design variables. RESULTS: Among non-Hispanic whites (NHW), history of any transfusion was inversely associated with NHL risk for men (OR 0.74; 95% CI 0.65-0.83) but not women (OR 0.92; 95% CI 0.83-1.03), pheterogeneity = 0.014. Transfusion history was not associated with risk in other racial/ethnic groups. There was no trend with the number of transfusions, time since first transfusion, age at first transfusion, or decade of first transfusion, and further adjustment for socioeconomic status, body mass index, smoking, alcohol use, and HCV seropositivity did not alter the results. Associations for NHW men were stronger in hospital-based (OR 0.56; 95% CI 0.45-0.70) but still apparent in population-based (OR 0.84; 95% CI 0.72-0.98) studies. CONCLUSIONS: In the setting of a literature reporting mainly null and some positive associations, and the lack of a clear methodologic explanation for our inverse association restricted to NHW men, the current body of evidence suggests that there is no association of blood transfusion with risk of NHL.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31246262

RESUMO

Objectives Some epidemiological studies have suggested positive associations between glyphosate use and non-Hodgkin lymphoma (NHL), but evidence is inconsistent and few studies could evaluate histological sub-types. Here, associations between glyphosate use and NHL incidence overall and by histological sub-type were evaluated in a pooled analysis of case-control studies. Methods The analysis included 1690 NHL cases [647 diffuse large B-cell lymphoma (DLBCL), 468 follicular lymphoma (FL), 171 small lymphocytic lymphoma (SLL), and 404 other sub-types] and 5131 controls. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) for NHL overall and sub-types with self-reported ever/never, duration, frequency, and lifetime-days of glyphosate use. Results Subjects who ever used glyphosate had an excess of NHL overall (OR 1.43, 95% CI 1.11-1.83). After adjustment for other pesticides, the OR for NHL overall with "ever use" was 1.13 (95% CI 0.84-1.51), with a statistically significant association for handling glyphosate >2 days/year (OR 1.73, 95% CI 1.02-2.94, P-trend=0.2). In pesticide-adjusted sub-type analyses, the ordinal measure of lifetime-days was statistically significant (P=0.03) for SLL, and associations were elevated, but not statistically significant, for ever years or days/year of use. Handling glyphosate >2 days/year had an excess of DLBCL (OR 2.14, 95% CI 1.07-4.28; P-trend=0.2). However, as with the other sub-types, consistent patterns of association across different metrics were not observed. Conclusions There was some limited evidence of an association between glyphosate use and NHL in this pooled analysis. Suggestive associations, especially for SLL, deserve additional attention.

5.
Cancer Epidemiol ; 60: 174-178, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31054466

RESUMO

INTRODUCTION: Breast cancer rates vary internationally and between immigrant and non-immigrant populations. We describe breast cancer incidence by birth region and country in British Columbia, Canada. METHODS: We linked population-based health and immigration databases for a population with >1.29 million immigrants to assess breast cancer incidence among immigrant and non-immigrant women. We report age-standardized incidence ratios (SIRs) by birth region and country using non-immigrant women as the standard. RESULTS: SIRs varied widely by both birth country and region. Low rates were found for South (SIR = 0.52, 95% CI: 0.47,0.59) and East Asian (SIR = 0.75, 95% CI: 0.72,0.79) women and a higher rate for Western Europeans (SIR = 1.15, 95% CI: 1.01,1.30). CONCLUSION: There is considerable variation in SIRs across some of British Columbia's largest immigrant populations and several demonstrate significantly different risk profiles compared to non-immigrants. These findings provide unique data to support breast cancer prevention and control.

6.
Mol Genet Genomic Med ; 7(6): e707, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31066241

RESUMO

BACKGROUND: Epidemiological studies consistently indicate that alcohol consumption is an independent risk factor for female breast cancer (BC). Although the aldehyde dehydrogenase 2 (ALDH2) polymorphism (rs671: Glu>Lys) has a strong effect on acetaldehyde metabolism, the association of rs671 with BC risk and its interaction with alcohol intake have not been fully elucidated. We conducted a pooled analysis of 14 case-control studies, with individual data on Asian ancestry women participating in the Breast Cancer Association Consortium. METHODS: We included 12,595 invasive BC cases and 12,884 controls for the analysis of rs671 and BC risk, and 2,849 invasive BC cases and 3,680 controls for the analysis of the gene-environment interaction between rs671 and alcohol intake for BC risk. The pooled odds ratios (OR) with 95% confidence intervals (CI) associated with rs671 and its interaction with alcohol intake for BC risk were estimated using logistic regression models. RESULTS: The Lys/Lys genotype of rs671 was associated with increased BC risk (OR = 1.16, 95% CI 1.03-1.30, p = 0.014). According to tumor characteristics, the Lys/Lys genotype was associated with estrogen receptor (ER)-positive BC (OR = 1.19, 95% CI 1.05-1.36, p = 0.008), progesterone receptor (PR)-positive BC (OR = 1.19, 95% CI 1.03-1.36, p = 0.015), and human epidermal growth factor receptor 2 (HER2)-negative BC (OR = 1.25, 95% CI 1.05-1.48, p = 0.012). No evidence of a gene-environment interaction was observed between rs671 and alcohol intake (p = 0.537). CONCLUSION: This study suggests that the Lys/Lys genotype confers susceptibility to BC risk among women of Asian ancestry, particularly for ER-positive, PR-positive, and HER2-negative tumor types.

7.
Environ Int ; 127: 199-205, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30928843

RESUMO

Organophosphates and carbamates have been among the most commonly used insecticides, with both agricultural and residential uses. Previous studies have suggested associations of non-Hodgkin lymphoma (NHL) with some of these chemicals; however, many studies have been limited in their ability to evaluate associations with lymphoma subtypes. We evaluated the use of eleven organophosphate and two carbamate insecticides in association with NHL in the North American Pooled Project, which includes data from case-control studies in the United States and Canada (1690 cases/5131 controls). We used unconditional logistic regression adjusting for potential confounders, including use of other pesticides, to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between these chemicals and NHL overall, and NHL subtypes, i.e., follicular (FL), diffuse large B-cell (DLBCL), small lymphocytic lymphoma (SLL) and others. Ever use of malathion was associated with increased risk of NHL overall (OR = 1.43; 95% CI: 1.14-1.81) compared with never users. Categories using tertiles of duration (<4 yrs., 4-12 yrs., and >12 yrs) also showed a significant exposure-response for increasing years of use of malathion and risk of NHL (OR<4vsUnex = 1.33 (0.88, 2.03), OR4-12vsUnex = 1.42 (1.02, 1.96), OR>12vsUnex = 1.55 (1.05, 2.28, p-trend < 0.01)). In addition, malathion use was statistically significantly associated with FL (OR = 1.58; 95% CI: 1.11-2.27) and DLBCL (OR = 1.61; 95% CI: 1.16-2.22) while there were no apparent associations with SLL or other subtypes, the p-value for heterogeneity across subtypes, however, was not significant. These results support previous studies suggesting an association between insecticide use and NHL overall, and provide new information on associations with NHL subtypes.

8.
Cancer Med ; 8(4): 1826-1834, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30791219

RESUMO

INTRODUCTION: The literature suggests that differential colorectal cancer (CRC) screening adherence exists between Canada's immigrant and nonimmigrant populations. This study explores the impact of Ontario's population screening program, ColonCancerCheck, on CRC screening uptake in immigrant and nonimmigrant population groups. METHODS: Data from 2005, 2007-2008, and 2011-2012 was obtained from the Canadian Community Health Survey, to represent the intervention periods (the time periods before, during, and after implementation of the ColonCancerCheck intervention). Multivariable logistic regression was used to examine the effect of immigration status on the risk of nonadherence to guideline-recommended CRC screening, and an interaction analysis was performed to determine whether the screening differential between immigrant and nonimmigrant populations changed upon introduction of the ColonCancerCheck program. RESULTS: Recent and long-term immigrants were both at increased risk of CRC screening nonadherence compared to the Canadian-born population (OR 3.73 (CI 2.25-6.18) and OR 1.24 (CI 1.13-1.36), respectively). While not statistically significant, there was an attenuation of the risk of nonadherence to screening for recent immigrants compared with Canadian-born individuals after the implementation of the ColonCancerCheck program. CONCLUSIONS: This study provides evidence of a screening differential between immigrants and nonimmigrants, and suggests that the implementation of the ColonCancerCheck screening program in Ontario may have increased colon screening uptake amongst recent immigrants. Further studies are needed to address the factors leading to inequities in immigrant CRC screening adherence.

9.
PLoS One ; 14(1): e0209010, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30601841

RESUMO

BACKGROUND: Inflammation contributes to breast cancer development through its effects on cell damage. This damage is usually dealt with by key genes involved in apoptosis and autophagy pathways. METHODS: We tested 206 single nucleotide polymorphisms (SNPs) in 54 genes related to inflammation, apoptosis and autophagy in a population-based breast cancer study of women of European (658 cases and 795 controls) and East Asian (262 cases and 127 controls) descent. Logistic regression was used to estimate odds ratios for breast cancer risk, and case-only analysis to compare breast cancer subtypes (defined by ER/PR/HER2 status), with adjustment for confounders. We assessed statistical interactions between the SNPs and lifestyle factors (smoking status, physical activity and body mass index). RESULTS AND CONCLUSION: Although no SNP was associated with breast cancer risk among women of European descent, we found evidence for an association among East Asians for rs1800925 (IL-13) and breast cancer risk (OR = 2.08; 95% CI: 1.32-3.28; p = 0.000779), which remained statistically significant after multiple testing correction (padj = 0.0350). This association was replicated in a meta-analysis of 4305 cases and 4194 controls in the Shanghai Breast Cancer Genetics Study (OR 1.12, 95% CI: 1.03-1.21, p = 0.011). Further, we found evidence of an interaction between rs7874234 (TSC1) and physical activity among women of East Asian descent.


Assuntos
Apoptose/fisiologia , Autofagia/fisiologia , Neoplasias da Mama/genética , Inflamação/genética , Adulto , Apoptose/genética , Autofagia/genética , Feminino , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único/genética , Receptores Estrogênicos/genética , Receptores de Progesterona/genética , Adulto Jovem
10.
Occup Environ Med ; 76(1): 22-29, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30541747

RESUMO

OBJECTIVE: To estimate the association between occupational polycyclic aromatic hydrocarbon (PAH) exposure and female breast cancer. METHODS: Lifetime work histories for 1130 cases and 1169 controls from British Columbia and Ontario (Canada) were assessed for PAH exposure using a job-exposure matrix based on compliance measurements obtained during US Occupational Safety and Health Administration workplace safety inspections. RESULTS: Exposure to any level of PAHs was associated with an increased risk of breast cancer (OR=1.32, 95% CI: 1.10 to 1.59), as was duration at high PAH exposure (for >7.4 years: OR=1.45, 95% CI: 1.10 to 1.91; ptrend=0.01), compared with women who were never exposed. Increased risk of breast cancer was most strongly associated with prolonged duration at high occupational PAH exposure among women with a family history of breast cancer (for >7.4 years: OR=2.79, 95% CI: 1.25 to 6.24; ptrend<0.01). CONCLUSIONS: Our study suggests that prolonged occupational exposure to PAH may increase breast cancer risk, especially among women with a family history of breast cancer.

11.
Sci Rep ; 8(1): 16293, 2018 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-30390014

RESUMO

Maintaining a healthy body weight, eating well and being physically active lowers cancer risk by 30%. However, the biology underlying these relationships is not well understood. We examined cross-sectional associations between metabolites and cancer preventive behaviors as well as the relevance to cancer-related pathways among 120 participants (50% men, mean BMI 26.6 kg/m2, mean age 54 years) with no history of smoking or cancer. Participants completed questionnaires, physical measurements and provided blood samples. Non-targeted nuclear magnetic resonance captured 223 metabolite measures. Factor analysis was performed separately for amino acid, fatty acid and lipoprotein groups. Multivariable-adjusted linear regression was used to evaluate associations between cancer preventive recommendations and metabolite-containing factors (p-value < 0.05, false discovery rate <0.20). An inflammation-related metabolite (glycoprotein acetylation) loaded strongly on a factor that was associated with excess adiposity (body fat ≥25% (men) or ≥30% (women) ß (SE) = 0.74 (0.18)) and not meeting physical activity recommendations (ß (SE) = 0.40 (0.20)). Insulin sensitivity-related metabolites including monounsaturated and polyunsaturated fats were lower among participants not meeting recommendations for adiposity, fruits and vegetables and physical activity while branched chain amino acids were higher. Cancer preventive behaviors were associated with complex metabolic signatures, including alterations in pathways known to be involved in cancer pathogenesis.

12.
J Occup Environ Med ; 60(10): 911-916, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30289833

RESUMO

OBJECTIVE: The aim of this study was to estimate the association between organochlorine pesticides and polychlorinated biphenyls (PCBs) and multiple myeloma (MM). METHODS: The risk of MM from organochlorine compounds was examined in a population-based case-control study in British Columbia, Canada. Congeners of PCBs and pesticides or pesticide metabolites were measured in plasma of 325 cases and 327 controls. RESULTS: Most organochlorine analytes showed a significant association with MM. The strongest association (highest vs lowest quartile) was oxychlordane (odds ratio = 7.44; 95% confidence interval = 4.19 to 13.21). No heterogeneity was detected between organochlorines levels and MM subtypes. Only oxychlordane and ß-hexachlorocyclohexane (ß-HCCH) were identified as significant independent predictors of MM. CONCLUSION: Our study provides evidence that organochlorines contribute to the risk of MM.

14.
J Agromedicine ; 23(3): 187-214, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30047858

RESUMO

OBJECTIVE: To conduct a literature review to determine the types of information that existing dermal pesticide monitoring data could provide for future pesticide exposure assessment in occupational epidemiology. METHODS: A systematic literature search was performed on eight online databases. Two screening phases with predetermined criteria identified the qualifying literature. Standard information and dermal pesticide monitoring data were recorded and summarized from each qualifying study to assess its usefulness for future pesticide exposure assessment. RESULTS: A total of 31 farm studies qualified for review; task information was used to standardize all farm job(s) evaluated into 5 job groups: operators, applicators, mixer-loaders, field workers, and flaggers. When attempting to compare dermal exposure levels between studies, two types of variation were identified: (1) variation in study focus and reporting and 2) variation in exposure levels. The former variation type prevented exposure level comparisons between studies. Within studies, exposure levels were compared across body parts to identify that which had the highest measured exposure and to determine if results were similar in other studies that evaluated the same farm job. Using studies that measured exposure for multiple farm jobs, within study comparisons of total body exposure were performed to evaluate work factors. CONCLUSION: Future dermal pesticide exposure monitoring studies should standardize reporting procedures, as suggested in this review, to allow for more extensive dermal data comparisons. Body parts with highest measured levels of dermal exposure were identified by farm job, along with work factors to be further investigated as potential dermal pesticide exposure determinants for farm workers.

15.
Cancer Med ; 7(8): 4044-4067, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29984906

RESUMO

Breast cancer screening programs operate across Canada providing mammography to women in target age groups with the goal of reducing breast cancer mortality through early detection of tumors. Disparities in breast screening participation among socio-demographic groups, including immigrants, have been reported in Canada. Our objectives were to: (1) assess breast screening participation and retention among immigrant and nonimmigrant women in British Columbia (BC), Canada; and (2) to characterize factors associated with screening among screening-age recent immigrant women in BC. We examined 2 population-based cohorts of women eligible for breast screening participation (537 783 women) and retention (281 052 women) using linked health and immigration data. Breast screening rates were presented according to socio-demographic and health-related variables stratified by birth country. Factors associated with screening among recent immigrant women were explored using Poisson regression. We observed marked variation in screening participation across birth country cohorts. Eastern European/Central Asian women showed low participation (37.9%) with rates from individual countries ranging from 35.0% to 49.0%. Participation rates for immigrant women from the most common birth countries, such as China/Macau/Hong Kong/Taiwan (45.7%), India (44.5%), the Philippines (45.9%), and South Korea (39.0%), were lower than the nonimmigrant rates (51.2%). Retention rates showed less variation by birth country; however, some disparities between immigrant and nonimmigrant groups persisted. Associations between screening indicators and study factors varied considerably across immigrant groups. Primary care physician visits were consistently positively associated with screening participation; this variable was also the only predictor associated with screening within each of the groups of recent immigrants. Our study provides unique data on both screening participation and retention among Canadian immigrant women compiled by individual country of birth. Our results are further demonstration that screening disparities exist among immigrant populations as well as in comparison with nonimmigrant women.

16.
CMAJ ; 190(23): E710-E717, 2018 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-29891475

RESUMO

BACKGROUND: Understanding the complex interaction of risk factors that increase the likelihood of developing common diseases is challenging. The Canadian Partnership for Tomorrow Project (CPTP) is a prospective cohort study created as a population-health research platform for assessing the effect of genetics, behaviour, family health history and environment (among other factors) on chronic diseases. METHODS: Volunteer participants were recruited from the general Canadian population for a confederation of 5 regional cohorts. Participants were enrolled in the study and core information obtained using 2 approaches: attendance at a study assessment centre for all study measures (questionnaire, venous blood sample and physical measurements) or completion of the core questionnaire (online or paper), with later collection of other study measures where possible. Physical measurements included height, weight, percentage body fat and blood pressure. Participants consented to passive follow-up through linkage with administrative health databases and active follow-up through recontact. All participant data across the 5 regional cohorts were harmonized. RESULTS: A total of 307 017 participants aged 30-74 from 8 provinces were recruited. More than half provided a venous blood sample and/or other biological sample, and 33% completed physical measurements. A total of 709 harmonized variables were created; almost 25% are available for all participants and 60% for at least 220 000 participants. INTERPRETATION: Primary recruitment for the CPTP is complete, and data and biosamples are available to Canadian and international researchers through a data-access process. The CPTP will support research into how modifiable risk factors, genetics and the environment interact to affect the development of cancer and other chronic diseases, ultimately contributing evidence to reduce the global burden of chronic disease.

17.
J Occup Environ Med ; 2018 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-29933318

RESUMO

OBJECTIVE: To estimate the association between organochlorine pesticides and polychlorinated biphenyls (PCBs) and multiple myeloma (MM). METHODS: The risk of MM from organochlorine compounds was examined in a population-based case-control study in British Columbia, Canada. Congeners of PCBs and pesticides or pesticide metabolites were measured in plasma of 325 cases and 327 controls. RESULTS: Most organochlorine analytes showed a significant association with MM. The strongest association (highest vs lowest quartile) was oxychlordane (OR = 7.44 95% CI = 4.19-13.21). No heterogeneity was detected between organochlorines levels and MM subtypes. Only oxychlordane and ß-hexachlorocyclohexane (ß-HCCH) were identified as significant independent predictors of MM. CONCLUSIONS: Our study provides evidence that organochlorines contribute to the risk of MM.

18.
Arch Osteoporos ; 13(1): 52, 2018 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-29721623

RESUMO

This study investigates, in women diagnosed with breast cancer, the feasibility of evaluating the effects of educational material and its delivery method, on bone health management. The study results suggest educational material may improve rates of bone mineral density testing. INTRODUCTION: Educational materials improve bone mineral density (BMD) testing rates in high-risk patients, but the effect is unknown in women diagnosed with breast cancer. Methods of delivering educational materials may also affect testing rates. The purposes of this study were to determine the feasibility of the protocol and to pilot-test the effects of educational material and its delivery methods on BMD testing rates. METHOD: Pilot randomized controlled trial with block randomization. Fifty-four women (aged 65-75 and diagnosed with breast cancer ≥ 3 years ago (2010-2012) and not taking osteoporosis medication) were recruited from February to May 2016 and randomized to three groups: control without educational material, educational material delivered by postal mail, and educational material delivered by patient choice of postal mail, email, or text messaging. Outcome measures were primarily evaluated using self-report questionnaires. RESULTS: The participation rate, defined as the proportion of eligible participants who consented to participate, was 39.1%. Primary outcome measure was obtained for 98% of the recruited women. During the 6-month follow-up period, BMD testing rates were significantly higher in the groups receiving educational materials by mail (26%, 95%CI = 10 to 49) and by patient choice (18%, 95%CI = 5 to 41), when compared with the control group (6%, 95%CI = 0.3 to 25). Educational material was associated with a 17% higher BMD testing rate. CONCLUSIONS: The study protocol is feasible for a large-scale study. The educational material intervention is broadly accepted by the study participants with a promising positive effect on BMD testing rates.

19.
Cancer Res ; 78(14): 4086-4096, 2018 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-29735552

RESUMO

A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of "heterozygote advantage" regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL = 1.31, 95% CI = 1.06-1.60; OR MZL = 1.45, 95% CI = 1.12-1.89) and class II HLA-DRB1 locus (OR DLBCL = 2.10, 95% CI = 1.24-3.55; OR MZL = 2.10, 95% CI = 0.99-4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci (P trend < 0.0001, FDR = 0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes.Significance: HLA gene diversity reduces risk for non-Hodgkin lymphoma. Cancer Res; 78(14); 4086-96. ©2018 AACR.

20.
Blood ; 131(23): 2541-2551, 2018 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-29674426

RESUMO

Inherited loci have been found to be associated with risk of chronic lymphocytic leukemia (CLL). A combined polygenic risk score (PRS) of representative single nucleotide polymorphisms (SNPs) from these loci may improve risk prediction over individual SNPs. Herein, we evaluated the association of a PRS with CLL risk and its precursor, monoclonal B-cell lymphocytosis (MBL). We assessed its validity and discriminative ability in an independent sample and evaluated effect modification and confounding by family history (FH) of hematological cancers. For discovery, we pooled genotype data on 41 representative SNPs from 1499 CLL and 2459 controls from the InterLymph Consortium. For validation, we used data from 1267 controls from Mayo Clinic and 201 CLL, 95 MBL, and 144 controls with a FH of CLL from the Genetic Epidemiology of CLL Consortium. We used odds ratios (ORs) to estimate disease associations with PRS and c-statistics to assess discriminatory accuracy. In InterLymph, the continuous PRS was strongly associated with CLL risk (OR, 2.49; P = 4.4 × 10-94). We replicated these findings in the Genetic Epidemiology of CLL Consortium and Mayo controls (OR, 3.02; P = 7.8 × 10-30) and observed high discrimination (c-statistic = 0.78). When jointly modeled with FH, PRS retained its significance, along with FH status. Finally, we found a highly significant association of the continuous PRS with MBL risk (OR, 2.81; P = 9.8 × 10-16). In conclusion, our validated PRS was strongly associated with CLL risk, adding information beyond FH. The PRS provides a means of identifying those individuals at greater risk for CLL as well as those at increased risk of MBL, a condition that has potential clinical impact beyond CLL.

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