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While hundreds of germline genetic variants have been associated with breast cancer risk, the mechanisms underlying the impacts of most of these variants on breast cancer remain uncertain. Metabolomics may offer valuable insights into the mechanisms underlying genetic risks of breast cancer. Among 143 cancer-free female participants, we used linear regression analyses to explore associations between the genetic risk of breast cancer, as determined by a previously developed polygenic risk score (PRS) that included 266 single-nucleotide polymorphisms (SNPs), and 223 measures of metabolites obtained from blood samples using nuclear magnetic resonance (NMR). A false discovery rate of 10% was applied to account for multiple comparisons. PRS was statistically significantly associated with 45 metabolite measures. These were primarily measures of very low-density lipoproteins (VLDLs) and high-density lipoproteins (HDLs), including triglycerides, cholesterol, and phospholipids. For example, the strongest effect was observed with the percent ratio of medium VLDL triglycerides to total lipids (0.53 unit increase in mean-standardized ln-transformed percent ratio per unit increase in PRS; q = 0.1). While larger-scale studies are needed to confirm these results, this exploratory study presents biologically plausible findings that are consistent with previously reported associations between lipids and breast cancer risk. If confirmed, these lipids could be targeted for lifestyle and pharmaceutical interventions among women at increased genetic risk of breast cancer.
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Introduction: There is conflicting evidence for the association between antihypertensive medications and colorectal cancer risk, possibly reflecting methodological limitations of previously conducted studies. Here, we aimed to clarify associations between commonly prescribed antihypertensive medication classes and colorectal cancer risk in a large, retrospective, cohort study. Methods: Using linked administrative data between 1996 and 2017 from British Columbia, we identified a cohort of 1,693,297 men and women who were 50 years of age or older, initially cancer-free and nonusers of antihypertensive medications. Medication use was parameterized as ever use, cumulative duration, and cumulative dose. Cox proportional hazard models were used to estimate hazard ratios (HRs) and associated 95% confidence intervals (95% CIs) for associations of time-varying medication use [angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), beta-blockers (BBs), calcium channel blockers (CCBs), and diuretics] with colorectal cancer risk. Results: There were 28,460 incident cases of colorectal cancer identified over the follow-up period (mean = 12.9 years). When medication use was assessed as ever/never, diuretics were associated with increased risk of colorectal cancer (HR 1.08, 95% CI 1.04-1.12). However, no similar association was observed with cumulative duration or cumulative dose of diuretics. No significant associations between the other four classes of medications and colorectal cancer risk were observed. Conclusion: No compelling evidence of associations between antihypertensive medications and colorectal cancer were observed.
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Multiple myeloma (MM) arises following malignant proliferation of plasma cells in the bone marrow, that secrete high amounts of specific monoclonal immunoglobulins or light chains, resulting in the massive production of unfolded or misfolded proteins. Autophagy can have a dual role in tumorigenesis, by eliminating these abnormal proteins to avoid cancer development, but also ensuring MM cell survival and promoting resistance to treatments. To date no studies have determined the impact of genetic variation in autophagy-related genes on MM risk. We performed meta-analysis of germline genetic data on 234 autophagy-related genes from three independent study populations including 13,387 subjects of European ancestry (6863 MM patients and 6524 controls) and examined correlations of statistically significant single nucleotide polymorphisms (SNPs; p < 1 × 10-9) with immune responses in whole blood, peripheral blood mononuclear cells (PBMCs), and monocyte-derived macrophages (MDM) from a large population of healthy donors from the Human Functional Genomic Project (HFGP). We identified SNPs in six loci, CD46, IKBKE, PARK2, ULK4, ATG5, and CDKN2A associated with MM risk (p = 4.47 × 10-4-5.79 × 10-14). Mechanistically, we found that the ULK4rs6599175 SNP correlated with circulating concentrations of vitamin D3 (p = 4.0 × 10-4), whereas the IKBKErs17433804 SNP correlated with the number of transitional CD24+CD38+ B cells (p = 4.8 × 10-4) and circulating serum concentrations of Monocyte Chemoattractant Protein (MCP)-2 (p = 3.6 × 10-4). We also found that the CD46rs1142469 SNP correlated with numbers of CD19+ B cells, CD19+CD3- B cells, CD5+IgD- cells, IgM- cells, IgD-IgM- cells, and CD4-CD8- PBMCs (p = 4.9 × 10-4-8.6 × 10-4) and circulating concentrations of interleukin (IL)-20 (p = 0.00082). Finally, we observed that the CDKN2Ars2811710 SNP correlated with levels of CD4+EMCD45RO+CD27- cells (p = 9.3 × 10-4). These results suggest that genetic variants within these six loci influence MM risk through the modulation of specific subsets of immune cells, as well as vitamin D3-, MCP-2-, and IL20-dependent pathways.
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Mieloma Múltiple , Humanos , Mieloma Múltiple/genética , Mieloma Múltiple/patología , Leucocitos Mononucleares/patología , Biomarcadores , Inmunoglobulina M , AutofagiaRESUMEN
BACKGROUND: Breast cancer screening utilization varies across immigrant and non-immigrant populations. Recent studies have also suggested that some immigrant populations in Canada present with a higher frequency of later-stage breast cancer compared to non-immigrants. Our study aimed to augment prior research by presenting breast cancer stage distributions and stage-specific breast cancer incidence rates for immigrant and non-immigrants in British Columbia, Canada. METHODS: We utilized a population-based cohort of more than 1.3 million women built from linked administrative health and immigration data sets. Age-standardized incidence rate ratios were generated to compare immigrant and non-immigrant groups. Poisson regression was used to assess the relative frequency of later stage diagnosis among immigrant groups compared to non-immigrants. RESULTS: Indian and Chinese immigrants both showed significantly lower stage I and stage II-IV incidence rates compared to non-immigrants. However, Indian immigrants showed a higher frequency of later stage tumours at diagnosis compared to non-immigrants, while in contrast Chinese immigrants showed a lower frequency of later stage tumours. Filipino immigrants showed similar stage-specific rates and stage at diagnosis compared to non-immigrants. CONCLUSIONS: Our findings highlight a need for continued surveillance of cancer among immigrant and non-immigrant populations and inquiry into reasons for differences in stage at diagnosis across groups.
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Neoplasias de la Mama , Emigrantes e Inmigrantes , Humanos , Femenino , Neoplasias de la Mama/diagnóstico , Emigración e Inmigración , Colombia Británica/epidemiología , IncidenciaRESUMEN
Non-Hodgkin lymphoma (NHL) is composed of a heterogeneous collection of subtypes with considerable differences in genetics, biology and aetiology. Studies to date on physical activity and NHL risk have not had sufficient sample size to evaluate whether associations differ by subtype. We pooled data from nine case-control studies to examine the association between moderate-to-vigorous intensity physical activity (MVPA) and risk of NHL overall and by subtype (diffuse large B-cell lymphoma, follicular lymphoma, chronic lymphocytic leukaemia/small lymphocytic lymphoma, marginal zone lymphoma and mature T-cell lymphoma). A total of 5653 cases and 9115 controls were included in the pooled analysis. Physical activity was harmonised across nine studies and modelled as study-specific tertiles. Multinomial logistic regression was used to estimate the association between physical activity and NHL, adjusting for confounders. The overall odds of NHL was 13% lower among participants in the most active tertile of MVPA compared to the least active tertile (adjusted odds ratio = 0.87, 95% CI = 0.80, 0.95). Similar decreases were observed across NHL subtypes. In summary, in this pooled analysis of case-control studies, physical activity was associated with a modest risk reduction for each NHL subtype examined and with overall NHL.
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Linfoma Folicular , Linfoma no Hodgkin , Humanos , Factores de Riesgo , Linfoma no Hodgkin/etiología , Linfoma no Hodgkin/complicaciones , Linfoma Folicular/epidemiología , Linfoma Folicular/etiología , Estudios de Casos y Controles , Ejercicio FísicoRESUMEN
By combining data from 160,500 individuals with breast cancer and 226,196 controls of Asian and European ancestry, we conducted genome- and transcriptome-wide association studies of breast cancer. We identified 222 genetic risk loci and 137 genes that were associated with breast cancer risk at a p < 5.0 × 10-8 and a Bonferroni-corrected p < 4.6 × 10-6, respectively. Of them, 32 loci and 15 genes showed a significantly different association between ER-positive and ER-negative breast cancer after Bonferroni correction. Significant ancestral differences in risk variant allele frequencies and their association strengths with breast cancer risk were identified. Of the significant associations identified in this study, 17 loci and 14 genes are located 1Mb away from any of the previously reported breast cancer risk variants. Pathways analyses including 221 putative risk genes identified multiple signaling pathways that may play a significant role in the development of breast cancer. Our study provides a comprehensive understanding of and new biological insights into the genetics of this common malignancy.
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Neoplasias de la Mama , Estudio de Asociación del Genoma Completo , Femenino , Humanos , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple/genética , Transcriptoma/genética , Neoplasias de la Mama/genética , Estudios de Casos y ControlesRESUMEN
BACKGROUND: Early detection of breast cancer improves survival, so identifying factors associated with stage at diagnosis may help formulate cancer prevention messages tailored for higher risk women. The goal of this study was to evaluate associations between multiple potential risk factors, including novel ones, measured before a breast cancer diagnosis and stage at diagnosis in women from Alberta, Canada. METHODS: Women enrolled in Alberta's Tomorrow Project completed health and lifestyle questionnaires on average 7 years before their breast cancer diagnosis. The association of previously identified and novel predictors with stage (I, II and III + IV) at diagnosis were simultaneously evaluated in partial proportional odds ordinal (PPO) regression models. RESULTS: The 492 women in this study were predominantly diagnosed in Stage 1 (51.4%), had college or university education (75.4%), were married or had a partner (74.6%), had been pregnant (90.2%), had taken birth control pills for any reason (86.8%), and had an average body mass index of 26.6. Most had at least one mammogram (83%) with five mammograms the average number. Nearly all reported previously having a breast health examination from a medical practitioner (92.5%). Statistically significant factors identified in the PPO model included protective ones (older age at diagnosis, high household income, parity, smoking, spending time in the sun during high ultraviolet times, having a mammogram and high daily protein intake) and ones that increased risk of later stage at diagnosis (a comorbidity, current stressful situations and high daily caloric intake). CONCLUSION: Shifting breast cancer stage at diagnosis downwards may potentially be achieved through cancer prevention programs that target higher risk groups such as women with co-morbidities, non-smokers and younger women who may be eligible for breast cancer screening.
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Neoplasias de la Mama , Alberta/epidemiología , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/epidemiología , Detección Precoz del Cáncer , Femenino , Humanos , Estilo de Vida , Mamografía , Factores de RiesgoRESUMEN
BACKGROUND: Despite the long-standing experience of rating the evidence for clinical preventive services, the delivery of effective clinical preventive services in Canada and elsewhere is less than optimal. We outline an approach used in British Columbia to assist in determining which effective clinical preventive services are worth doing. METHODS: We calculated the clinically preventable burden and cost-effectiveness for 28 clinical preventive services that received a 'strong or conditional (weak) recommendation for' by the Canadian Task Force on Preventive Health Care or an 'A' or 'B' rating by the United States Preventive Services Task Force. Clinically preventable burden is the total quality adjusted life years that could be gained if the clinical preventive services were delivered at recommended intervals to a British Columbia birth cohort of 40,000 individuals over the years of life that the service is recommended. Cost-effectiveness is the net cost per quality adjusted life year gained. RESULTS: Clinical preventive services with the highest population impact and best value for money include services that address tobacco use in adolescents and adults, exclusive breastfeeding, and screening for hypertension and other cardiovascular disease risk factors followed by appropriate pharmaceutical treatment. In addition, alcohol misuse screening and brief counseling, one-time screening for hepatitis C virus infection in British Columbia adults born between 1945 and 1965, and screening for type 2 diabetes approach these high-value clinical preventive services. CONCLUSIONS: These results enable policy makers to say with some confidence what preventive manoeuvres are worth doing but further work is required to determine the best way to deliver these services to all those eligible and to establish what supportive services are required. After all, if a clinical preventive service is worth doing, it is worth doing well.
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Diabetes Mellitus Tipo 2 , Adolescente , Adulto , Colombia Británica , Atención a la Salud , Humanos , Servicios Preventivos de Salud , Años de Vida Ajustados por Calidad de Vida , Estados UnidosRESUMEN
PURPOSE: Antihypertensive medications may impact colorectal cancer risk. We conducted a systematic review and meta-analysis of associations, with colorectal cancer risk, of five classes of antihypertensive medications: angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), beta-blockers (BBs), calcium channel blockers (CCBs), and diuretics. METHODS: A systematic search was conducted in MEDLINE, Embase, Web of Science, and the Cochrane library to identify relevant studies evaluating associations of ACEIs, ARBs, BBs, CCBs, and diuretics with colorectal cancer risk. Meta-analytic risk ratios (RRs) and corresponding 95% confidence intervals (95% CIs) were calculated using the inverse variance method. RESULTS: No overall significant associations with colorectal cancer risk were observed; ACEIs (5 studies) RR 1.05, 95% CI 0.91-1.23, ARBs (5 studies) RR 0.94, 95% CI 0.80-1.11, BBs (4 studies) RR 1.00, 95% CI 0.92-1.08, CCBs (4 studies) RR 1.02, 95% CI 0.88-1.18, and diuretics (6 studies) RR 1.02, 95% CI 0.90-1.17. There was considerable heterogeneity across studies, partly explained by differences in study design and location. When stratified by study location, there was significantly reduced colorectal cancer risk for ARB use in Asian populations (2 studies, RR 0.69, 95% CI 0.58-0.83). CONCLUSION: No significant colorectal cancer risk with ACEIs, BBs, CCBs, or diuretics was observed. ARB use may be associated with decreased risk of colorectal cancer in Asian populations, although additional studies in diverse populations are needed to confirm associations and help understand possible reasons for geographical differences.
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Neoplasias Colorrectales , Hipertensión , Antagonistas Adrenérgicos beta/uso terapéutico , Antagonistas de Receptores de Angiotensina/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antihipertensivos/uso terapéutico , Bloqueadores de los Canales de Calcio/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/etiología , Diuréticos/efectos adversos , Humanos , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiologíaRESUMEN
PURPOSE: Polycyclic aromatic hydrocarbons (PAHs) are a group of environmental pollutants associated with multiple cancers, including female breast cancer. Several xenobiotic metabolism genes (XMGs), including the CYP450 family, play an important role in activating and detoxifying PAHs, and variations in the activity of the enzymes they encode can impact this process. This study aims to examine the association between XMGs and breast cancer, and to assess whether these variants modify the effects of PAH exposure on breast cancer risk. METHODS: In a case-control study in Vancouver, British Columbia, and Kingston, Ontario, 1037 breast cancer cases and 1046 controls had DNA extracted from blood or saliva and genotyped for 138 single nucleotide polymorphisms (SNPs) and tagSNPs in 27 candidate XMGs. Occupational PAH exposure was assessed using a measurement-based job-exposure matrix. RESULTS: An association between genetic variants and breast cancer was observed among six XMGs, including increased risk among the minor allele carriers of AKR1C3 variant rs12387 (OR 2.71, 95% CI 1.42-5.19) and AKR1C4 variant rs381267 (OR 2.50, 95% CI 1.23-5.07). Heterogeneous effects of occupational PAH exposure were observed among carriers of AKR1C3/4 variants, as well as the PTGS2 variant rs5275. CONCLUSION: Our findings support an association between SNPs of XMGs and female breast cancer, including novel genetic variants that modify the toxicity of PAH exposure. These results highlight the interplay between genetic and environmental factors, which can be helpful in understanding the modifiable risks of breast cancer and its complex etiology.
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Neoplasias de la Mama/epidemiología , Interacción Gen-Ambiente , Hidrocarburos Policíclicos Aromáticos/toxicidad , Xenobióticos/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Miembro C3 de la Familia 1 de las Aldo-Ceto Reductasas/genética , Canadá/epidemiología , Estudios de Casos y Controles , Ciclooxigenasa 2/genética , Femenino , Heterocigoto , Humanos , Persona de Mediana Edad , Exposición Profesional , Oxidorreductasas/genética , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: Despite the increasing trend of cutaneous malignant melanoma (CMM) incidence in Canada, especially among females, few risk factors other than ultraviolet radiation exposure, have been identified. AIM: We conducted a case-control study of 406 CMM cases and 181 controls to evaluate the potential impact of body burdens of various persistent organic pollutants on CMM risk. METHODS: Detailed data on potential confounding factors, including lifetime repeated sun exposure and skin reaction to repeated sun exposure, were collected. Gas chromatography tandem mass spectrometry was used to assay plasma levels of 14 polychlorinated biphenyl (PCB) congeners and 11 organochlorine (OC) pesticides among cases and controls. RESULTS: Statistically significant trends of increased CMM risk were observed with increasing plasma concentrations of multiple PCB congeners, including PCBs 138, 153, 170, 180, 183 and 187. For example, compared to lowest plasma concentration quartile of PCB-138, the second, third and fourth quartiles were associated with 1.7 (95% CI: 0.9-2.9), 2.3 (95% CI: 1.3-4.1) and 2.4 (95% CI: 1.3-4.5) -fold increased risks of CMM, respectively. Similarly, increasing plasma concentrations of several OC pesticides (i.e., ß-HCH, HCB, Mirex, oxychlordane and trans-Nonachlor) showed statistically significant trends with increased CMM risk. For example, compared to lowest plasma concentration quartile of ß-HCH, the second, third and fourth quartiles were associated with 1.3 (95% CI: 0.7-2.3), 2.1 (95% CI: 1.2-3.7) and 2.3 (95% CI: 1.2-4.4) -fold increased risks of CMM, respectively. CONCLUSION: Plasma levels of several persistent organic pollutants were highly correlated, suggesting that observed associations were not necessarily independent of each other. Given the highly correlated nature of exposure to PCB and OC analytes, sophisticated analyses that consider complex mixtures should be considered in future studies.
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Contaminantes Ambientales , Melanoma , Plaguicidas , Estudios de Casos y Controles , Contaminantes Ambientales/efectos adversos , Contaminantes Ambientales/análisis , Femenino , Humanos , Melanoma/diagnóstico , Melanoma/epidemiología , Melanoma/etiología , Contaminantes Orgánicos Persistentes , Plaguicidas/efectos adversos , Plaguicidas/análisis , Neoplasias Cutáneas , Rayos Ultravioleta , Melanoma Cutáneo MalignoRESUMEN
We investigated the impact of new systemic therapies approved in Canada for colorectal cancer on the frequency, intensity and duration of oncology clinic and infusion visits over five treatment phases from diagnosis (P1, P3) to treatment (P2, P4) of primary and metastatic disease, respectively, and during the last 6 months of life (P5). In total, 15,157 adult patients with newly diagnosed colorectal cancer and referred between 2000 and 2012 to any cancer clinic in British Columbia, Canada, were included. Frequency, intensity and duration of medical oncology clinic visits (CVs), oncology infusions (OIs) and oncology prescriptions (OPs) were measured by treatment phase. Mean, total and adjusted total duration for CVs increased for P1-5. CVs increased in P1-5, and in P1-4 when adjusted by treatment length. Adjusted and unadjusted OIs decreased in P1 coinciding with the introduction of an oral treatment option, but increased in P2-5. Mean OI duration increased in P1-5, while total and adjusted total decreased in P1 and increased in P2-5. OPs increased in P2-4, but were unchanged in P1 and P5. Multi-fold increases in resources and time required per patient were also observed, which have significant implications for demand projections in cancer care planning and delivery. In conclusion, patients required more visits in almost all treatment phases, visits on average took longer and patients were in treatment for longer periods of time.
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Neoplasias Colorrectales , Pacientes Ambulatorios , Adulto , Atención Ambulatoria , Instituciones de Atención Ambulatoria , Canadá , Neoplasias Colorrectales/tratamiento farmacológico , HumanosRESUMEN
Colorectal cancer (CRC) is a leading cause of morbidity and mortality in Canada. CRC screening and other factors associated with early-stage disease can improve CRC treatment efficacy and survival. This study examined factors associated with CRC stage at diagnosis among male and female adults using data from a large prospective cohort study in Alberta, Canada. Baseline data were obtained from healthy adults aged 35-69 years participating in Alberta's Tomorrow Project. Factors associated with CRC stage at diagnosis were evaluated using Partial Proportional Odds models. Analyses were stratified to examine sex-specific associations. A total of 267 participants (128 males and 139 females) developed CRC over the study period. Among participants, 43.0% of males and 43.2% of females were diagnosed with late-stage CRC. Social support, having children, and caffeine intake were predictors of CRC stage at diagnosis among males, while family history of CRC, pregnancy, hysterectomy, menopausal hormone therapy, lifetime number of Pap tests, and household physical activity were predictive of CRC stage at diagnosis among females. These findings highlight the importance of sex differences in susceptibility to advanced CRC diagnosis and can help inform targets for cancer prevention programs to effectively reduce advanced CRC and thus improve survival.
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Neoplasias Colorrectales , Detección Precoz del Cáncer , Adulto , Anciano , Alberta/epidemiología , Niño , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Ejercicio Físico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
BACKGROUND: Observational studies show that digital breast tomosynthesis (DBT) combined with digital mammography (DM) can reduce recall rates and increases rates of breast cancer detection. The objective of this study was to examine the cost-effectiveness of DBT plus DM versus DM alone in British Columbia and to identify parameters that can improve the efficiency of breast cancer screening programs. METHODS: We conducted an economic analysis based on data from a cohort of screening participants in the BC Cancer Breast Screening Program. The decision model simulated lifetime costs and outcomes for participants in breast cancer screening who were aged 40-74 years between 2012 and 2017. We analyzed rates of health care resource utilization, health state costs and estimated incremental cost-effectiveness ratios (ICERs), to measure incremental cost differences per quality-adjusted life years (QALYs) gained from the addition of DBT to DM-based screening, from the government payer's perspective. RESULTS: The model simulated economic outcomes for 112 249 screening participants. We found that the ICER was highly sensitive to recall rate reductions and insensitive to parameters related to cancer detection. If DBT plus DM can reduce absolute recall rates by more than 2.1%, the base-case scenario had an ICER of $17 149 per QALY. At a willingness-to-pay threshold of $100 000 per QALY, more than 95% of the probabilistic simulations favoured the adoption of DBT plus DM versus DM alone. The ICER depended heavily on the ability of DBT plus DM to reduce recall rates. INTERPRETATION: The addition of DBT to DM would be considered cost-effective owing to the low positive predictive value of screening with DM alone. Reductions in false-positive recall rates should be monitored closely.
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Neoplasias de la Mama , Mama/diagnóstico por imagen , Detección Precoz del Cáncer , Mamografía , Adulto , Anciano , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/economía , Neoplasias de la Mama/epidemiología , Colombia Británica/epidemiología , Análisis Costo-Beneficio , Técnicas de Apoyo para la Decisión , Detección Precoz del Cáncer/economía , Detección Precoz del Cáncer/métodos , Femenino , Humanos , Mamografía/economía , Mamografía/métodos , Valor Predictivo de las Pruebas , Utilización de Procedimientos y Técnicas/economía , Años de Vida Ajustados por Calidad de VidaRESUMEN
Gene expression profiling can be used for predicting survival in multiple myeloma (MM) and identifying patients who will benefit from particular types of therapy. Some germline single nucleotide polymorphisms (SNPs) act as expression quantitative trait loci (eQTLs) showing strong associations with gene expression levels. We performed an association study to test whether eQTLs of genes reported to be associated with prognosis of MM patients are directly associated with measures of adverse outcome. Using the genotype-tissue expression portal, we identified a total of 16 candidate genes with at least one eQTL SNP associated with their expression with P < 10-7 either in EBV-transformed B-lymphocytes or whole blood. We genotyped the resulting 22 SNPs in 1327 MM cases from the International Multiple Myeloma rESEarch (IMMEnSE) consortium and examined their association with overall survival (OS) and progression-free survival (PFS), adjusting for age, sex, country of origin and disease stage. Three polymorphisms in two genes (TBRG4-rs1992292, TBRG4-rs2287535 and ENTPD1-rs2153913) showed associations with OS at P < .05, with the former two also associated with PFS. The associations of two polymorphisms in TBRG4 with OS were replicated in 1277 MM cases from the International Lymphoma Epidemiology (InterLymph) Consortium. A meta-analysis of the data from IMMEnSE and InterLymph (2579 cases) showed that TBRG4-rs1992292 is associated with OS (hazard ratio = 1.14, 95% confidence interval 1.04-1.26, P = .007). In conclusion, we found biologically a plausible association between a SNP in TBRG4 and OS of MM patients.
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Apirasa/genética , Perfilación de la Expresión Génica/métodos , Proteínas Mitocondriales/genética , Mieloma Múltiple/mortalidad , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo , Proteínas de Unión al ARN/genética , Anciano , Femenino , Estudios de Asociación Genética , Mutación de Línea Germinal , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/genética , Análisis de SupervivenciaRESUMEN
Since 2008, girls in British Columbia (BC), Canada, have been offered HPV vaccination through a school-based, publicly funded immunization program. The oldest birth cohort eligible for the vaccination program was born in 1994 and uptake is on average 63%. To evaluate the impact of the HPV vaccine in BC, ecological trends in cervical intraepithelial neoplasia (CIN) rates were assessed in young women before and after the implementation of the HPV vaccination program. Information on all Pap smears and histopathological abnormalities, in calendar years 2004-2017 in women 16-28 years of age in BC were obtained from the population-based BC Cancer Cervix Screening Program database. Rates of CIN 2 and 3 were calculated as the number of cases divided by the number of cytology specimens for that period. Rate ratios (RR) were calculated by negative binomial piecewise regression. Age-centered incidence rates of CIN 2 and 3 in BC declined significantly among women 16-23 years of age after HPV vaccine introduction compared to before vaccine introduction. The overall reduction postvaccination for CIN2 and 3 in women 16-23 years was respectively 62% (95% CI 54-68%) and 65% (95% CI 58-71%). Age-specific rates for CIN2 significantly declined for those 18-22 years of age and for those 19, 20 and 23 years of age for CIN3. Among women 24-28 years of age no decline in CIN2 and 3 rate over time was observed. The observed reduction in CIN 2 and 3 rates since the introduction of the school-based HPV vaccine program might illustrate the population impact of the BC provincial school-based HPV vaccination program.
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Programas de Inmunización/métodos , Papillomaviridae/efectos de los fármacos , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/administración & dosificación , Displasia del Cuello del Útero/prevención & control , Neoplasias del Cuello Uterino/prevención & control , Vacunación/estadística & datos numéricos , Adolescente , Adulto , Colombia Británica/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Papillomaviridae/inmunología , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/virología , Pronóstico , Instituciones Académicas , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/virología , Frotis Vaginal/métodos , Adulto Joven , Displasia del Cuello del Útero/epidemiología , Displasia del Cuello del Útero/virologíaRESUMEN
An understanding of relationships between different constructs of the neighbourhood environment and diet quality is needed to inform public health interventions. This study investigated associations between material deprivation, social deprivation and population density with diet quality in a cohort of 19,973 Canadian adults aged 35 to 69 years within the Atlantic PATH cohort study. Diet quality, a metric of how well diet conforms to recommendations was determined from a 24-item food frequency questionnaire. Neighbourhood environment data were derived from dissemination area level Census data. Two deprivation indices were evaluated: material and social deprivation, which reflect access to goods and amenities and social relationships. Multi-level models were used to estimate relationships (mean differences and 95% CI) between neighbourhood environment and diet quality, adjusting for covariates. Mean diet quality was lower in the most socially deprived neighbourhoods compared to the least socially deprived: -0.56, 95% CI (-0.88, -0.25). Relationships between diet quality and population density differed between urban and rural areas (p-interaction < 0.0001). In rural areas, diet quality was higher in intermediate-density neighbourhoods: 0.54, 95% CI (0.05, 1.03). In urban areas, diet quality was lower in intermediate-density and the most-dense neighbourhoods: -0.84, 95% CI (-1.28, -0.40) and -0.72, 95% CI (-1.20, -0.25). Our findings suggest socially deprived and high-density neighbourhoods are associated with lower diet quality and possible urban-rural differences in neighbourhood environment-diet quality relationships. Additional studies are needed to determine the temporal nature of relationships and whether differences in diet quality are meaningful.
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Dieta , Densidad de Población , Factores Socioeconómicos , Adulto , Anciano , Canadá , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Características de la Residencia , Población Rural , Población UrbanaRESUMEN
Polygenic risk scores (PRS) have been shown to predict breast cancer risk in European women, but their utility in Asian women is unclear. Here we evaluate the best performing PRSs for European-ancestry women using data from 17,262 breast cancer cases and 17,695 controls of Asian ancestry from 13 case-control studies, and 10,255 Chinese women from a prospective cohort (413 incident breast cancers). Compared to women in the middle quintile of the risk distribution, women in the highest 1% of PRS distribution have a ~2.7-fold risk and women in the lowest 1% of PRS distribution has ~0.4-fold risk of developing breast cancer. There is no evidence of heterogeneity in PRS performance in Chinese, Malay and Indian women. A PRS developed for European-ancestry women is also predictive of breast cancer risk in Asian women and can help in developing risk-stratified screening programmes in Asia.
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Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/genética , Herencia Multifactorial , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Asia/epidemiología , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/etnología , Estudios de Casos y Controles , Europa (Continente)/epidemiología , Femenino , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Persona de Mediana Edad , Oportunidad Relativa , Pronóstico , RiesgoRESUMEN
BACKGROUND: Tattoos may cause a variety of adverse reactions in the body, including immune reactions and infections. However, it is unknown whether tattoos may increase the risk of lymphatic cancers such as non-Hodgkin lymphoma (NHL) and multiple myeloma. METHODS: Participants from two population-based case-control studies were included in logistic regression models to examine the association between tattoos and risk of NHL and multiple myeloma. RESULTS: A total of 1,518 participants from the NHL study (737 cases) and 742 participants from the multiple myeloma study (373 cases) were included in the analyses. No statistically significant associations were found between tattoos and risk of NHL or multiple myeloma after adjusting for age, sex, ethnicity, education, body mass index, and family history. CONCLUSIONS: We did not identify any significant associations between tattoos and risk of multiple myeloma, NHL, or NHL subtypes in these studies. IMPACT: Though biologically plausible, tattoos were not associated with increased risk of NHL or multiple myeloma in this study. Future studies with greater detail regarding tattoo exposure may provide further insights.
Asunto(s)
Neoplasias Hematológicas/etiología , Tatuaje/efectos adversos , Colombia Británica , Canadá , Femenino , Neoplasias Hematológicas/fisiopatología , Humanos , MasculinoRESUMEN
Insecticide use has been linked to increased risk of non-Hodgkin lymphoma (NHL), however, findings of epidemiologic studies have been inconsistent, particularly for NHL subtypes. We analyzed 1690 NHL cases and 5131 controls in the North American Pooled Project (NAPP) to investigate self-reported insecticide use and risk of NHL overall and by subtypes: follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL) and small lymphocytic lymphoma (SLL). Odds ratios (OR) and 95% confidence intervals for each insecticide were estimated using logistic regression. Subtype-specific associations were evaluated using ASSET (Association analysis for SubSETs). Increased risks of multiple NHL subtypes were observed for lindane (OR = 1.60, 1.20-2.10: FL, DLCBL, SLL), chlordane (OR = 1.59, 1.17-2.16: FL, SLL) and DDT (OR = 1.36, 1.06-1.73: DLBCL, SLL). Positive trends were observed, within the subsets with identified associations, for increasing categories of exposure duration for lindane (Ptrend = 1.7 × 10-4 ), chlordane (Ptrend = 1.0 × 10-3 ) and DDT (Ptrend = 4.2 × 10-3 ), however, the exposure-response relationship was nonlinear. Ever use of pyrethrum was associated with an increased risk of FL (OR = 3.65, 1.45-9.15), and the relationship with duration of use appeared monotonic (OR for >10 years: OR = 5.38, 1.75-16.53; Ptrend = 3.6 × 10-3 ). Our analysis identified several novel associations between insecticide use and specific NHL subtypes, suggesting possible etiologic heterogeneity in the context of pesticide exposure.