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1.
Eur J Epidemiol ; 35(11): 1025-1042, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32959149

RESUMO

While childbearing protects against risk of epithelial ovarian cancer (EOC), few studies have explored the impact on maternal EOC risk of sex of offspring, which may affect the maternal environment during pregnancy. We performed a pooled analysis among parous participants from 12 case-controls studies comprising 6872 EOC patients and 9101 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable logistic regression for case-control associations and polytomous logistic regression for histotype-specific associations, all adjusted for potential confounders. In general, no associations were found between offspring sex and EOC risk. However, compared to bearing only female offspring, bearing one or more male offspring was associated with increased risk of mucinous EOC (OR = 1.45; 95% CI = 1.01-2.07), which appeared to be limited to women reporting menarche before age 13 compared to later menarche (OR = 1.71 vs 0.99; P-interaction = 0.02). Bearing increasing numbers of male offspring was associated with greater risks of mucinous tumors (OR = 1.31, 1.84, 2.31, for 1, 2 and 3 or more male offspring, respectively; trend-p = 0.005). Stratifying by hormonally-associated conditions suggested that compared to bearing all female offspring, bearing a male offspring was associated with lower risk of endometrioid cancer among women with a history of adult acne, hirsutism, or polycystic ovary syndrome (OR = 0.49, 95% CI = 0.28-0.83) but with higher risk among women without any of those conditions (OR = 1.64 95% CI = 1.14-2.34; P-interaction = 0.003). Offspring sex influences the childbearing-EOC risk relationship for specific histotypes and conditions. These findings support the differing etiologic origins of EOC histotypes and highlight the importance of EOC histotype-specific epidemiologic studies. These findings also suggest the need to better understand how pregnancy affects EOC risk.

2.
Cancer Epidemiol Biomarkers Prev ; 29(10): 1983-1992, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32699080

RESUMO

BACKGROUND: Lung cancer remains the leading cause of cancer death worldwide, with 15% to 20% occurring in never smokers. To assess genetic determinants for prognosis among never smokers, we conducted a genome-wide investigation in the International Lung Cancer Consortium (ILCCO). METHODS: Genomic and clinical data from 1,569 never-smoking patients with lung cancer of European ancestry from 10 ILCCO studies were included. HRs and 95% confidence intervals of overall survival were estimated. We assessed whether the associations were mediated through mRNA expression-based 1,553 normal lung tissues from the lung expression quantitative trait loci (eQTL) dataset and Genotype-Tissue Expression (GTEx). For cross-ethnicity generalization, we assessed the associations in a Japanese study (N = 887). RESULTS: One locus at 13q22.2 was associated with lung adenocarcinoma survival at genome-wide level, with carriers of rs12875562-T allele exhibiting poor prognosis [HR = 1.71 (1.41-2.07), P = 3.60 × 10-8], and altered mRNA expression of LMO7DN in lung tissue (GTEx, P = 9.40 × 10-7; Lung eQTL dataset, P = 0.003). Furthermore, 2 of 11 independent loci that reached the suggestive significance level (P < 10-6) were significant eQTL affecting mRNA expression of nearby genes in lung tissues, including CAPZB at 1p36.13 and UBAC1 at 9q34.3. One locus encoding NWD2/KIAA1239 at 4p14 showed associations in both European [HR = 0.50 (0.38-0.66), P = 6.92 × 10-7] and Japanese populations [HR = 0.79 (0.67-0.94), P = 0.007]. CONCLUSIONS: Based on the largest genomic investigation on the lung cancer prognosis of never smokers to date, we observed that lung cancer prognosis is affected by inherited genetic variants. IMPACT: We identified one locus near LMO7DN at genome-wide level and several potential prognostic genes with cis-effect on mRNA expression. Further functional genomics work is required to understand their role in tumor progression.

3.
Int J Cancer ; 2020 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-32574374

RESUMO

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.

4.
J Natl Cancer Inst ; 2020 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-32324875

RESUMO

BACKGROUND: Body mass index (BMI) is a complex phenotype that may interact with genetic variants to influence colorectal cancer risk. METHODS: We tested multiplicative statistical interactions between BMI (per 5 kg·m2) and approximately 2.7 million single nucleotide polymorphisms (SNPs) with colorectal cancer risk among 14,059 colorectal cancer case (53.2% women) and 14,416 control (53.8% women) participants. All analyses were stratified by sex a priori. Statistical methods included two-step (i.e., Cocktail method) and single-step (i.e., case-control logistic regression and a joint 2-degree of freedom test) procedures. All statistical tests were two-sided. RESULTS: Each 5 kg·m2 increase in BMI was associated with higher risks of colorectal cancer, less so for women (odds ratio [OR]: 1.14; 95% confidence intervals [CI]: 1.11-1.18; p-value: 9.75 x 10-17) than for men (OR: 1.26; 95% CI: 1.20-1.32; p-value: 2.13 x 10-24). The two-step Cocktail method identified an interaction for women, but not men, between BMI and a SMAD7 intronic variant at 18q21.1 (rs4939827; p-observed: 0.0009; p-threshold: 0.005). A joint 2-degree of freedom test was consistent with this finding for women (joint p-value: 2.43 x 10-10). Each 5 kg·m2 increase in BMI was more strongly associated with colorectal cancer risk for women with the rs4939827-CC genotype (OR: 1.24; 95% CI: 1.16-1.32; p-value: 2.60 x 10-10) than for women with the CT (OR: 1.14; 95% CI: 1.09-1.19; p-value: 1.04 x 10-8) or TT (OR: 1.07; 95% CI: 1.01-1.14; p-value: 0.02) genotypes. CONCLUSION: These results provide novel insights on a potential mechanism through which a SMAD7 variant, previously identified as a susceptibility locus for colorectal cancer, and BMI may influence colorectal cancer risk for women.

5.
Cancer Causes Control ; 31(6): 583-599, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32314107

RESUMO

PURPOSE: The purpose of this study was to investigate associations between pesticide exposures and risk of Hodgkin lymphoma (HL) using data from the North American Pooled Project (NAPP). METHODS: Three population-based studies conducted in Kansas, Nebraska, and six Canadian provinces (HL = 507, Controls = 3886) were pooled to estimate odds ratios and 95% confidence intervals for single (never/ever) and multiple (0, 1, 2-4, ≥ 5) pesticides used, duration (years) and, for select pesticides, frequency (days/year) using adjusted logistic regression models. An age-stratified analysis (≤ 40/ > 40 years) was conducted when numbers were sufficient. RESULTS: In an analysis of 26 individual pesticides, ever use of terbufos was significantly associated with HL (OR: 2.53, 95% CI 1.04-6.17). In age-stratified analyses, associations were stronger among those ≤ 40 years of age. No significant associations were noted among those > 40 years old; however, HL cases ≤ 40 were three times more likely to report ever using dimethoate (OR: 3.76 95% CI 1.02-33.84) and almost twice as likely to have ever used malathion (OR: 1.86 95% CI 1.00-3.47). Those ≤ 40 years of age reporting use of 5 + organophosphate insecticides had triple the odds of HL (OR: 3.00 95% CI 1.28-7.03). Longer duration of use of 2,4-D, ≥ 6 vs. 0 years, was associated with elevated odds of HL (OR: 2.59 95% CI 1.34-4.97). CONCLUSION: In the NAPP, insecticide use may increase the risk of HL, but results are based on small numbers.


Assuntos
Exposição Ambiental/estatística & dados numéricos , Doença de Hodgkin/epidemiologia , Praguicidas , Adulto , Canadá/epidemiologia , Humanos , Kansas/epidemiologia , Nebraska/epidemiologia
6.
Scand J Work Environ Health ; 45(6): 600-609, 2019 11 01.
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.


Assuntos
Glicina/análogos & derivados , Linfoma não Hodgkin/epidemiologia , Exposição Ocupacional/efeitos adversos , Praguicidas/envenenamento , Adulto , Idoso , Idoso de 80 Anos ou mais , Canadá/epidemiologia , Estudos de Casos e Controles , Causalidade , Feminino , Glicina/envenenamento , Humanos , Linfoma não Hodgkin/induzido quimicamente , Linfoma não Hodgkin/classificação , Masculino , Pessoa de Meia-Idade , Medição de Risco , Estados Unidos/epidemiologia , Adulto Jovem
7.
Int J Epidemiol ; 48(3): 822-830, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31211375

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder with an estimated prevalence of 4-21% in reproductive aged women. Recently, the Ovarian Cancer Association Consortium (OCAC) reported a decreased risk of invasive ovarian cancer among women with self-reported PCOS. However, given the limitations of self-reported PCOS, the validity of these observed associations remains uncertain. Therefore, we sought to use Mendelian randomization with genetic markers as a proxy for PCOS, to examine the association between PCOS and ovarian cancer. METHODS: Utilizing 14 single nucleotide polymorphisms (SNPs) previously associated with PCOS we assessed the association between genetically predicted PCOS and ovarian cancer risk, overall and by histotype, using summary statistics from a previously conducted genome-wide association study (GWAS) of ovarian cancer among European ancestry women within the OCAC (22 406 with invasive disease, 3103 with borderline disease and 40 941 controls). RESULTS: An inverse association was observed between genetically predicted PCOS and invasive ovarian cancer risk: odds ratio (OR)=0.92 [95% confidence interval (CI)=0.85-0.99; P = 0.03]. When results were examined by histotype, the strongest inverse association was observed between genetically predicted PCOS and endometrioid tumors (OR = 0.77; 95% CI = 0.65-0.92; P = 0.003). Adjustment for individual-level body mass index, oral contraceptive use and parity did not materially change the associations. CONCLUSION: Our study provides evidence for a relationship between PCOS and reduced ovarian cancer risk, overall and among specific histotypes of invasive ovarian cancer. These results lend support to our previous observational study results. Future studies are needed to understand mechanisms underlying this association.


Assuntos
Adenocarcinoma de Células Claras/epidemiologia , Adenocarcinoma Mucinoso/epidemiologia , Carcinoma Endometrioide/epidemiologia , Neoplasias Ovarianas/epidemiologia , Síndrome do Ovário Policístico/epidemiologia , Feminino , Humanos , Análise da Randomização Mendeliana , Neoplasias Císticas, Mucinosas e Serosas/epidemiologia , Síndrome do Ovário Policístico/genética
8.
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.


Assuntos
Carbamatos/toxicidade , Inseticidas/toxicidade , Linfoma não Hodgkin/induzido quimicamente , Organofosfatos/toxicidade , Idoso , Canadá , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Praguicidas , Fatores de Risco , Estados Unidos
9.
Cancer Epidemiol ; 58: 25-32, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30445228

RESUMO

BACKGROUND: There is inadequate evidence to determine whether there is an effect of alcohol consumption on lung cancer risk. We conducted a pooled analysis of data from the International Lung Cancer Consortium and the SYNERGY study to investigate this possible association by type of beverage with adjustment for other potential confounders. METHODS: Twenty one case-control studies and one cohort study with alcohol-intake data obtained from questionnaires were included in this pooled analysis (19,149 cases and 362,340 controls). Adjusted odds ratios (OR) or hazard ratios (HR) with corresponding 95% confidence intervals (CI) were estimated for each measure of alcohol consumption. Effect estimates were combined using random or fixed-effects models where appropriate. Associations were examined for overall lung cancer and by histological type. RESULTS: We observed an inverse association between overall risk of lung cancer and consumption of alcoholic beverages compared to non-drinkers, but the association was not monotonic. The lowest risk was observed for persons who consumed 10-19.9 g/day ethanol (OR vs. non-drinkers = 0.78; 95% CI: 0.67, 0.91), where 1 drink is approximately 12-15 g. This J-shaped association was most prominent for squamous cell carcinoma (SCC). The association with all lung cancer varied little by type of alcoholic beverage, but there were notable differences for SCC. We observed an association with beer intake (OR for ≥20 g/day vs nondrinker = 1.42; 95% CI: 1.06, 1.90). CONCLUSIONS: Whether the non-monotonic associations we observed or the positive association between beer drinking and squamous cell carcinoma reflect real effects await future analyses and insights about possible biological mechanisms.


Assuntos
Adenocarcinoma/epidemiologia , Consumo de Bebidas Alcoólicas/efeitos adversos , Carcinoma de Células Escamosas/epidemiologia , Neoplasias Pulmonares/epidemiologia , Adenocarcinoma/etiologia , Idoso , Bebidas Alcoólicas/efeitos adversos , Carcinoma de Células Escamosas/etiologia , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Neoplasias Pulmonares/etiologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Inquéritos e Questionários
10.
Occup Environ Med ; 75(11): 798-806, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30121582

RESUMO

OBJECTIVES: To investigate the association between occupational exposure to aromatic hydrocarbon solvents and risk of multiple myeloma (MM) in a large, consortium-based study. METHODS: We pooled data on 2854 cases and 10 743 controls from nine studies participating in the InterLymph consortium. Occupational exposures to benzene, toluene and xylene were assigned by a job-exposure matrix, coupled with 'correction' of exposure probability by self-reported or expert-assessed exposure from the individual studies. Cumulative intensity was calculated as the job-specific exposure intensity multiplied by job duration, summed across jobs. Associations were estimated using logistic regression, with inclusion of covariates for study matching factors and other potential confounders. We repeated our main analysis using random-effects meta-analysis to evaluate heterogeneity of effect. RESULTS: Benzene, toluene and xylene were each associated with MM. For the three solvents, the highest quartile of high-probability cumulative intensity exposure (vs unexposed) was associated with 42% to 63% increased risks of MM. Associations with toluene and xylene exposures were fairly consistent and robust to sensitivity analyses. The estimated effect for benzene was moderately heterogeneous between the studies. Each solvent's association with MM was stronger for exposure occurring within 20 years of diagnosis than with exposure lagged by more than 20 years. CONCLUSIONS: Our study adds important evidence for a role of aromatic hydrocarbon solvents in causation of MM. The difficulty in disentangling individual compounds in this group and a lack of data on potential carcinogenicity of toluene and xylene, in widespread current use, underscore a need for further epidemiological evaluation.


Assuntos
Hidrocarbonetos Aromáticos/toxicidade , Mieloma Múltiplo/induzido quimicamente , Doenças Profissionais/induzido quimicamente , Exposição Ocupacional/efeitos adversos , Solventes/toxicidade , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/análise , Fatores de Risco
11.
Carcinogenesis ; 39(9): 1135-1140, 2018 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-29924316

RESUMO

To identify genetic variation associated with lung cancer risk, we performed a genome-wide association analysis of 685 lung cancer cases that had a family history of two or more first or second degree relatives compared with 744 controls without lung cancer that were genotyped on an Illumina Human OmniExpressExome-8v1 array. To ensure robust results, we further evaluated these findings using data from six additional studies that were assembled through the Transdisciplinary Research on Cancer of the Lung Consortium comprising 1993 familial cases and 33 690 controls. We performed a meta-analysis after imputation of all variants using the 1000 Genomes Project Phase 1 (version 3 release date September 2013). Analyses were conducted for 9 327 222 SNPs integrating data from the two sources. A novel variant on chromosome 4p15.31 near the LCORL gene and an imputed rare variant intergenic between CDKN2A and IFNA8 on chromosome 9p21.3 were identified at a genome-wide level of significance for squamous cell carcinomas. Additionally, associations of CHRNA3 and CHRNA5 on chromosome 15q25.1 in sporadic lung cancer were confirmed at a genome-wide level of significance in familial lung cancer. Previously identified variants in or near CHRNA2, BRCA2, CYP2A6 for overall lung cancer, TERT, SECISPB2L and RTEL1 for adenocarcinoma and RAD52 and MHC for squamous carcinoma were significantly associated with lung cancer.


Assuntos
Adenocarcinoma/genética , Carcinoma de Células Escamosas/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/genética , Estudos de Casos e Controles , Cromossomos Humanos Par 15/genética , Cromossomos Humanos Par 4 , Cromossomos Humanos Par 9/genética , Humanos , Pulmão/patologia , Anamnese , Polimorfismo de Nucleotídeo Único/genética
12.
Nutr J ; 17(1): 55, 2018 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-29793493

RESUMO

BACKGROUND: Dietary patterns are commonly used in epidemiological research, yet there have been few studies assessing if and how research results may vary across dietary patterns. This study aimed to estimate the risk of mortality/recurrence/metastasis using different dietary patterns and comparison amongst the patterns. METHODS: Dietary patterns were identified by Cluster Analysis (CA), Principal Component Analysis (PCA), Alternate Mediterranean Diet score (altMED), Recommended Food Score (RFS) and Dietary Inflammatory Index (DII) scores using a 169-item food frequency questionnaire. Five hundred thirty-two colorectal cancer patients diagnosed between 1999 and 2003 in Newfoundland were followed-up until 2010. Overall Mortality (OM) and combined Mortality, Recurrence or Metastasis (cMRM) were identified. Comparisons were made with adjusted Cox proportional Hazards Ratios (HRs), correlation coefficients and the distributions of individuals in defined clusters by quartiles of factor and index scores. RESULTS: One hundred and seventy cases died from all causes and 29 had a cancer recurrence/metastasis during follow-up. Processed meats as classified by PCA (HR 1.82; 95% confidence interval (CI) 1.07-3.09), clusters characterized by meat and dairy products (HR 2.19; 95% CI 1.03-4.67) and total grains, sugar, soft drinks (HR 1.95; 95% CI 1.13-3.37) were associated with a higher risk of cMRM. Poor adherence to AltMED increased the risk of all-cause OM (HR 1.62; 95% CI 1.04-2.56). Prudent vegetable, high sugar pattern, RFS and DII had no significant association with both OM and cMRM. CONCLUSION: Estimation of OM and cMRM varied across dietary patterns which is attributed to the differences in the foundation of each pattern.


Assuntos
Neoplasias Colorretais/mortalidade , Dieta/estatística & dados numéricos , Adulto , Idoso , Análise por Conglomerados , Estudos de Coortes , Registros de Dieta , Dieta Mediterrânea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/epidemiologia , Terra Nova e Labrador/epidemiologia , Avaliação Nutricional , Modelos de Riscos Proporcionais , Fatores de Risco , Inquéritos e Questionários , Taxa de Sobrevida
13.
BMC Cancer ; 18(1): 155, 2018 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-29409465

RESUMO

BACKGROUND: The rs2282679 A>C polymorphism in the vitamin D binding protein gene is associated with lower circulating levels of vitamin D. We investigated associations of this SNP with colorectal cancer (CRC) risk and survival and whether the associations vary by dietary vitamin D intake and tumor molecular phenotype. METHODS: A population-based case-control study identified 637 incident CRC cases (including 489 participants with follow-up data on mortality end-points) and 489 matched controls. Germline DNA samples were genotyped with the Illumina Omni-Quad 1 Million chip in cases and the Affymetrix Axiom® myDesign™ Array in controls. Logistic regression examined the association between the rs2282679 polymorphism and CRC risk with inclusion of potential confounders. Kaplan-Meier curves and multivariable Cox models assessed the polymorphism relative to overall survival (OS) and disease-free survival (DFS). RESULTS: The rs2282679 polymorphism was not associated with overall CRC risk; there was evidence, however, of effect modification by total vitamin D intake (Pinteraction = 0.019). Survival analyses showed that the C allele was correlated with poor DFS (per-allele HR, 1.36; 95%CI, 1.05-1.77). The association of rs2282679 on DFS was limited to BRAF wild-type tumors (HR, 1.58; 95%CI, 1.12-2.23). For OS, the C allele was associated with higher all-cause mortality among patients with higher levels of dietary vitamin D (HR, 2.11; 95%CI, 1.29-3.74), calcium (HR, 1.93; 95%CI, 1.08-3.46), milk (HR, 2.36; 95%CI, 1.26-4.44), and total dairy product intakes (HR, 2.03; 95%CI, 1.11-3.72). CONCLUSION: The rs2282679 SNP was not associated with overall CRC risk, but may be associated with survival after cancer diagnosis. The association of this SNP on survival among CRC patients may differ according to dietary vitamin D and calcium intakes and according to tumor BRAF mutation status.


Assuntos
Neoplasias Colorretais/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único , Proteína de Ligação a Vitamina D/genética , Idoso , Estudos de Casos e Controles , Dieta , Feminino , Frequência do Gene , Genótipo , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Vitamina D/administração & dosagem , Vitaminas/administração & dosagem
14.
Cancer Epidemiol Biomarkers Prev ; 27(2): 174-182, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29141849

RESUMO

Background: Polycystic ovary syndrome (PCOS), and one of its distinguishing characteristics, oligomenorrhea, have both been associated with ovarian cancer risk in some but not all studies. However, these associations have been rarely examined by ovarian cancer histotypes, which may explain the lack of clear associations reported in previous studies.Methods: We analyzed data from 14 case-control studies including 16,594 women with invasive ovarian cancer (n = 13,719) or borderline ovarian disease (n = 2,875) and 17,718 controls. Adjusted study-specific ORs were calculated using logistic regression and combined using random-effects meta-analysis. Pooled histotype-specific ORs were calculated using polytomous logistic regression.Results: Women reporting menstrual cycle length >35 days had decreased risk of invasive ovarian cancer compared with women reporting cycle length ≤35 days [OR = 0.70; 95% confidence interval (CI) = 0.58-0.84]. Decreased risk of invasive ovarian cancer was also observed among women who reported irregular menstrual cycles compared with women with regular cycles (OR = 0.83; 95% CI = 0.76-0.89). No significant association was observed between self-reported PCOS and invasive ovarian cancer risk (OR = 0.87; 95% CI = 0.65-1.15). There was a decreased risk of all individual invasive histotypes for women with menstrual cycle length >35 days, but no association with serous borderline tumors (Pheterogeneity = 0.006). Similarly, we observed decreased risks of most invasive histotypes among women with irregular cycles, but an increased risk of borderline serous and mucinous tumors (Pheterogeneity < 0.0001).Conclusions: Our results suggest that menstrual cycle characteristics influence ovarian cancer risk differentially based on histotype.Impact: These results highlight the importance of examining ovarian cancer risk factors associations by histologic subtype. Cancer Epidemiol Biomarkers Prev; 27(2); 174-82. ©2017 AACR.


Assuntos
Ciclo Menstrual/fisiologia , Oligomenorreia/complicações , Neoplasias Ovarianas/etiologia , Neoplasias Ovarianas/patologia , Síndrome do Ovário Policístico/complicações , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Razão de Chances , Oligomenorreia/fisiopatologia , Neoplasias Ovarianas/fisiopatologia , Síndrome do Ovário Policístico/fisiopatologia , Fatores de Risco , Autorrelato , Fatores de Tempo
15.
Nutrition ; 42: 69-74, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28870481

RESUMO

OBJECTIVE: Chronic inflammation is implicated in causing cancer. Diet plays an important role in regulating chronic inflammation by altering circulating levels of inflammatory biomarkers. Effect of single food or nutrient on cancer often is inconclusive; perhaps due to dietary interactions and multicolinearity. The aim of this study was to determine prediagnostic inflammatory potential of overall diet in relation to risk for colorectal cancer (CRC). METHODS: In all, 547 patients with CRC from Newfoundland Familial Colorectal Cancer Registry and 685 controls from the general population were identified. Data on sociodemographic, medical history, lifestyle, and a 169-item food frequency questionnaire were collected retrospectively from both groups. Energy-adjusted Dietary Inflammatory Index (DII) score was calculated and used as both categorical and continuous variables for analysis. Odds ratio was estimated using multivariable logistic regression after adjusting potential confounders. A linear test for trend was performed using the median value in each quartile. RESULTS: Overall energy-adjusted mean DII score was -0.81 (range -5.19 to 6.93). Cases (-0.73 ± 1.5) had slightly higher DII scores than controls (-0.89 ± 1.6; P = 0.04). After adjusting the potential confounders, a statistically significant association was found between DII score and CRC risk. Using DII as a continuous variable (odds ratio [OR]continuous 1.10, 95% confidence interval [CI] 1.01-1.20) and categorical variable (ORquartile 1 versus 4 1.65, 95% CI 1.13-2.42; Ptrend = 0.02). CONCLUSION: Our findings indicate that proinflammatory diets are associated with an increased risk for CRC in the Newfoundland population.


Assuntos
Neoplasias Colorretais/epidemiologia , Dieta/métodos , Inflamação/epidemiologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terra Nova e Labrador/epidemiologia , Fatores de Risco
16.
Br J Cancer ; 117(6): 898-906, 2017 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-28765616

RESUMO

BACKGROUND: Increased serum levels of vitamin D and calcium have been associated with lower risks of colorectal cancer (CRC) incidence and mortality. These inverse associations may be mediated by the vitamin D receptor (VDR) and the calcium-sensing receptor (CASR). We investigated genetic variants in VDR and CASR for their relevance to CRC prognosis. METHODS: A population-based cohort of 531 CRC patients diagnosed from 1999 to 2003 in Newfoundland and Labrador, Canada, was followed for mortality and cancer recurrence until April 2010. Germline DNA samples were genotyped with the Illumina Omni-Quad 1 Million chip. Multivariate Cox models assessed 41 tag single-nucleotide polymorphisms and relative haplotypes on VDR and CASR in relation to all-cause mortality (overall survival, OS) and disease-free survival (DFS). RESULTS: Gene-level associations were observed between VDR and the DFS of rectal cancer patients (P=0.037) as well as between CASR and the OS of colon cancer patients (P=0.014). Haplotype analysis within linkage blocks of CASR revealed the G-G-G-G-G-A-C haplotype (rs10222633-rs10934578-rs3804592-rs17250717-A986S-R990G-rs1802757) to be associated with a decreased OS of colon cancer (HR, 3.15; 95% CI, 1.66-5.96). Potential interactions were seen among prediagnostic dietary calcium intake with the CASR R990G (Pint=0.040) and the CASR G-T-G-G-G-G-C haplotype for rs10222633-rs10934578-rs3804592-rs17250717-A986S-R990G-rs1802757 (Pint=0.017), with decreased OS time associated with these variants limited to patients consuming dietary calcium below the median, although the stratified results were not statistically significant after correction for multiple testing. CONCLUSIONS: Polymorphic variations in VDR and CASR may be associated with survival after a diagnosis of CRC.


Assuntos
Neoplasias do Colo/genética , Neoplasias do Colo/mortalidade , Variação Genética , Recidiva Local de Neoplasia , Receptores de Calcitriol/genética , Receptores de Detecção de Cálcio/genética , Neoplasias Retais/genética , Neoplasias Retais/mortalidade , Dieta/efeitos adversos , Intervalo Livre de Doença , Feminino , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Terra Nova e Labrador , Análise de Sequência com Séries de Oligonucleotídeos , Polimorfismo de Nucleotídeo Único , Modelos de Riscos Proporcionais
17.
Br J Cancer ; 116(7): 964-971, 2017 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-28208158

RESUMO

BACKGROUND: Various epidemiologic factors have been shown to influence the risk of ovarian cancer development. Given the high fatality associated with this disease, it is of interest to evaluate the association of prediagnostic hormonal, reproductive, and lifestyle exposures with ovarian cancer-specific survival. METHODS: We included 1421 patients with invasive epithelial ovarian cancer diagnosed in Ontario, Canada. Clinical information was obtained from medical records and prediagnostic exposure information was collected by telephone interview. Survival status was determined by linkage to the Ontario Cancer Registry. Proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for ovarian cancer-specific mortality associated with each exposure. Analyses were stratified by histologic subtype to further investigate the associations of risk factors on ovarian cancer-specific mortality. RESULTS: After a mean follow-up of 9.48 years (range 0.59-20.32 years), 655 (46%) women had died of ovarian cancer. Parity (ever) was associated with a significant 29% decreased mortality risk compared with nulliparity (HR=0.71; 95% CI 0.54-0.93; P=0.01). There was a borderline significant association between ever use of oestrogen-containing hormone replacement therapy (HRT) and mortality (HR=0.79; 95% CI 0.62-1.01; P=0.06). A history of cigarette smoking was associated with a significant 25% increased risk of death compared with never smoking (HR=1.25; 95% CI 1.01-1.54; P=0.04). Women with a greater cumulative number of ovulatory cycles had a significantly decreased risk of ovarian cancer-specific death (HR=0.63; 95% CI 0.43-0.94; P=0.02). Increasing BMI (kg m-2) 5 years before diagnosis was associated with an increased risk of death (HR=1.17; 95% CI 1.07-1.28; P=0.0007). Other hormonal or lifestyle factors were not significantly associated with ovarian cancer-specific mortality. CONCLUSIONS: Parity, ovulatory cycles, smoking, and BMI may affect survival following the diagnosis of ovarian cancer. Whether or not oestrogen-containing HRT use is beneficial for survival requires further evaluation.


Assuntos
Adenocarcinoma de Células Claras/mortalidade , Adenocarcinoma Mucinoso/mortalidade , Cistadenocarcinoma Seroso/mortalidade , Neoplasias do Endométrio/mortalidade , Terapia de Reposição Hormonal/mortalidade , Neoplasias Ovarianas/mortalidade , Adenocarcinoma de Células Claras/diagnóstico , Adenocarcinoma de Células Claras/epidemiologia , Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Mucinoso/epidemiologia , Adulto , Idoso , Canadá/epidemiologia , Cistadenocarcinoma Seroso/diagnóstico , Cistadenocarcinoma Seroso/epidemiologia , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/epidemiologia , Fatores Epidemiológicos , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/epidemiologia , Paridade , Gravidez , Prognóstico , História Reprodutiva , Adulto Jovem
18.
Int J Cancer ; 140(9): 1976-1984, 2017 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-28120396

RESUMO

It is not clear whether alcohol consumption is associated with lung cancer risk. The relationship is likely confounded by smoking, complicating the interpretation of previous studies. We examined the association of alcohol consumption and lung cancer risk in a large pooled international sample, minimizing potential confounding of tobacco consumption by restricting analyses to never smokers. Our study included 22 case-control and cohort studies with a total of 2548 never-smoking lung cancer patients and 9362 never-smoking controls from North America, Europe and Asia within the International Lung Cancer Consortium (ILCCO) and SYNERGY Consortium. Alcohol consumption was categorized into amounts consumed (grams per day) and also modelled as a continuous variable using restricted cubic splines for potential non-linearity. Analyses by histologic sub-type were included. Associations by type of alcohol consumed (wine, beer and liquor) were also investigated. Alcohol consumption was inversely associated with lung cancer risk with evidence most strongly supporting lower risk for light and moderate drinkers relative to non-drinkers (>0-4.9 g per day: OR = 0.80, 95% CI = 0.70-0.90; 5-9.9 g per day: OR = 0.82, 95% CI = 0.69-0.99; 10-19.9 g per day: OR = 0.79, 95% CI = 0.65-0.96). Inverse associations were found for consumption of wine and liquor, but not beer. The results indicate that alcohol consumption is inversely associated with lung cancer risk, particularly among subjects with low to moderate consumption levels, and among wine and liquor drinkers, but not beer drinkers. Although our results should have no relevant bias from the confounding effect of smoking we cannot preclude that confounding by other factors contributed to the observed associations. Confounding in relation to the non-drinker reference category may be of particular importance.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Neoplasias Pulmonares/epidemiologia , Fumar/efeitos adversos , Idoso , Bebidas Alcoólicas/efeitos adversos , Ásia/epidemiologia , Estudos de Casos e Controles , Estudos de Coortes , Europa (Continente)/epidemiologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , América do Norte/epidemiologia , Fatores de Risco
19.
Fam Cancer ; 16(1): 29-34, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27631815

RESUMO

Recent studies suggest that mutations in the partner and localizer of BRCA2 (PALB2) gene may predispose to ovarian cancer. It is of importance to clarify the prevalence and penetrance of PALB2 mutations in an unselected population so that clinical recommendations for prevention can be implemented. We evaluated the prevalence of germline mutations in PALB2 among 1421 epithelial ovarian cancer patients and 4300 European controls from the National Heart, Lung, and Blood Institute's Exome Sequencing Project dataset. Clinical information was obtained from medical records and survival status was determined by linkage. PALB2 coding exons were sequenced using next generation sequencing technology. Of the 1421 patients, three (0.21 %) had a germline PALB2 mutation compared to two of the 4300 control subjects (0.05 %). The mean age at diagnosis was 59 years (range 55-62) and all three women died within 2 years of diagnosis. A PALB2 mutation was associated with a four-fold, albeit not significant, increased risk of ovarian cancer (OR = 4.55; 95 % CI 0.76-27.24; P = 0.10). These results suggest that germline PALB2 mutations are rare. The true effect of such mutations on ovarian cancer risk require further study before the clinical relevance of inherited PALB2 mutations is established.


Assuntos
Mutação em Linhagem Germinativa , Neoplasias Epiteliais e Glandulares/genética , Proteínas Nucleares/genética , Neoplasias Ovarianas/genética , Proteínas Supressoras de Tumor/genética , Carcinoma Epitelial do Ovário , Proteína do Grupo de Complementação N da Anemia de Fanconi , Feminino , Humanos , Pessoa de Meia-Idade , Taxa de Mutação , Neoplasias Epiteliais e Glandulares/patologia , Ontário , Neoplasias Ovarianas/patologia
20.
Br J Haematol ; 175(1): 87-101, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27330041

RESUMO

Family clusters of multiple myeloma (MM) suggest disease heritability. Nevertheless, patterns of inheritance and the importance of genetic versus environmental risk factors in MM aetiology remain unclear. We pooled data from eleven case-control studies from the International Multiple Myeloma Consortium to characterize the association of MM risk with having a first-degree relative with a history of a lympho-haematapoietic cancer. Unconditional logistic regression models, adjusted for study, sex, age and education level, were used to estimate associations between MM risk and having a first-degree relative with a history of non-Hodgkin lymphoma, Hodgkin lymphoma, leukaemia or MM. Sex, African American race/ethnicity and age were explored as effect modifiers. A total of 2843 cases and 11 470 controls were included. MM risk was elevated in association with having a first-degree relative with any lympho-haematapoietic cancer (Odds Ratio (OR) = 1·29, 95% Confidence Interval (CI): 1·08-1·55). The association was particularly strong for having a first-degree relative with MM (OR = 1·90, 95% CI: 1·26-2·87), especially among men (OR = 4·13, 95% CI: 2·17-7·85) and African Americans (OR = 5·52, 95% CI: 1·87-16·27).These results support the hypothesis that genetic inheritance plays a role in MM aetiology. Future studies are warranted to characterize interactions of genetic markers with environmental exposures.


Assuntos
Neoplasias Hematológicas/epidemiologia , Mieloma Múltiplo/epidemiologia , Idoso , Estudos de Casos e Controles , Grupos de Populações Continentais , Grupos Étnicos , Família , Feminino , Neoplasias Hematológicas/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/etiologia , Razão de Chances , Medição de Risco , Fatores de Risco , Fatores Sexuais
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