RESUMO
Nutrition may impact bladder cancer survival. We examined the association between diet quality and overall and bladder cancer-specific survival. Bladder cancer cases from a population-based study reported pre-diagnosis diet. Diet quality was assessed using the 2010 Alternate Healthy Eating Index (AHEI-2010). Vital status was ascertained from the National Death Index. Adjusted hazard ratios (HR) and 95% confidence intervals (CI) were estimated using proportional hazards and competing risks regression models. Overall AHEI-2010 adherence was not associated with overall or bladder cancer-specific survival among non-muscle invasive bladder cancer (NMIBC) cases (HR, 1.00; 95% CI, 0.98-1.01; HR, 1.00; 95% CI, 0.97-1.02) or muscle invasive bladder cancer (MIBC) cases (HR, 0.99; 95% CI, 0.96-1.03; HR, 1.01, 95% CI 0.97-1.06). AHEI-2010 sugar-sweetened beverages adherence was associated with poorer overall survival (HR, 1.04; 95% CI, 1.01-1.08) and AHEI-2010 sodium adherence was associated with better overall and bladder cancer-specific survival after NMIBC diagnosis (HR, 0.92, 95% CI, 0.85-1.00; HR, 0.82; 95% CI, 0.68-0.98). AHEI-2010 fruit adherence was associated with poorer overall and bladder cancer-specific survival after MIBC diagnosis (HR, 1.17; 95% CI, 1.02-1.33; HR, 1.26; 95% CI, 1.03-1.55). Consumption of sugar-sweetened beverages, sodium, and fruit, not overall AHEI-2010 adherence, may be associated with bladder cancer survival.
Assuntos
Neoplasias da Bexiga Urinária , Dieta , Dieta Saudável , Humanos , Modelos de Riscos Proporcionais , SódioRESUMO
PURPOSE: We examined the interaction between common genetic bladder cancer variants, diet quality, and bladder cancer risk in a population-based case-control study conducted in New England. METHODS: At the time of enrollment, 806 bladder cancer cases and 974 controls provided a DNA sample and completed a diet history questionnaire. Diet quality was assessed using the 2010 Alternate Healthy Eating Index (AHEI-2010) score. Single nucleotide polymorphisms (SNPs) reported in genome-wide association studies to be associated with bladder cancer risk were combined into a polygenic risk score and also examined individually for interaction with the AHEI-2010. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression. RESULTS: A 1-standard deviation increase in polygenic risk score was associated with higher bladder cancer risk (OR, 1.34; 95% CI 1.21-1.49). Adherence to the AHEI-2010 was not associated with bladder cancer risk (OR, 0.99; 95% CI 0.98-1.00) and the polygenic risk score did not appear to modify the association between the AHEI-2010 and bladder cancer risk. In single-SNP analyses, rs8102137 (bladder cancer risk allele, C) modified the association between the AHEI-2010 total score and bladder cancer risk, with the strongest evidence for the AHEI-2010 long chain fat guideline (OR for TT, 0.92; 95% CI 0.87-0.98; OR for CT, 1.02; 95% CI 0.96-1.08; OR for CC, 1.03; 95% CI 0.93-1.14; p for interaction, 0.02). CONCLUSIONS: In conclusion, rs8102137 near the cyclin E1 gene ( CCNE1 ) may be involved in gene-diet interactions for bladder cancer risk.
Assuntos
Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/epidemiologia , Neoplasias da Bexiga Urinária/genética , Estudo de Associação Genômica Ampla , Estudos de Casos e Controles , Dieta , Polimorfismo de Nucleotídeo Único , Ciclinas , DNARESUMO
Breast cancer is the most common solid organ malignancy and the most frequent cause of cancer death among women worldwide. Previous research has yielded insights into its genetic etiology, but there remains a gap in the understanding of genetic factors that contribute to risk, and particularly in the biological mechanisms by which genetic variation modulates risk. The National Cancer Institute's "Up for a Challenge" (U4C) competition provided an opportunity to further elucidate the genetic basis of the disease. Our group leveraged the seven datasets made available by the U4C organizers and data from the publicly available UK Biobank cohort to examine associations between imputed gene expression and breast cancer risk. In particular, we used reference datasets describing the breast tissue and whole blood transcriptomes to impute expression levels in breast cancer cases and controls. In trans-ethnic meta-analyses of U4C and UK Biobank data, we found significant associations between breast cancer risk and the expression of RCCD1 (joint p-value: 3.6x10-06) and DHODH (p-value: 7.1x10-06) in breast tissue, as well as a suggestive association for ANKLE1 (p-value: 9.3x10-05). Expression of RCCD1 in whole blood was also suggestively associated with disease risk (p-value: 1.2x10-05), as were expression of ACAP1 (p-value: 1.9x10-05) and LRRC25 (p-value: 5.2x10-05). While genome-wide association studies (GWAS) have implicated RCCD1 and ANKLE1 in breast cancer risk, they have not identified the remaining three genes. Among the genetic variants that contributed to the predicted expression of the five genes, we found 23 nominally (p-value < 0.05) associated with breast cancer risk, among which 15 are not in high linkage disequilibrium with risk variants previously identified by GWAS. In summary, we used a transcriptome-based approach to investigate the genetic underpinnings of breast carcinogenesis. This approach provided an avenue for deciphering the functional relevance of genes and genetic variants involved in breast cancer.
Assuntos
Neoplasias da Mama/genética , Proteínas de Transporte/genética , Proteínas Ativadoras de GTPase/genética , Predisposição Genética para Doença , Proteínas de Membrana/genética , Locos de Características Quantitativas/genética , Mama/metabolismo , Mama/patologia , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Proteínas de Transporte/sangue , Endonucleases/sangue , Endonucleases/genética , Etnicidade , Feminino , Proteínas Ativadoras de GTPase/sangue , Estudo de Associação Genômica Ampla , Humanos , Proteínas de Membrana/sangue , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Transcriptoma/genéticaRESUMO
While elevated blood cholesterol has been associated with an increased risk of colorectal cancer (CRC) in observational studies, causality is uncertain. Here we apply a Mendelian randomisation (MR) analysis to examine the potential causal relationship between lipid traits and CRC risk. We used single nucleotide polymorphisms (SNPs) associated with blood levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) as instrumental variables (IV). We calculated MR estimates for each risk factor with CRC using SNP-CRC associations from 9,254 cases and 18,386 controls. Genetically predicted higher TC was associated with an elevated risk of CRC (odds ratios (OR) per unit SD increase = 1.46, 95% confidence interval [CI]: 1.20-1.79, p = 1.68 × 10-4 ). The pooled ORs for LDL, HDL, and TG were 1.05 (95% CI: 0.92-1.18, p = 0.49), 0.94 (95% CI: 0.84-1.05, p = 0.27), and 0.98 (95% CI: 0.85-1.12, p = 0.75) respectively. A genetic risk score for 3-hydoxy-3-methylglutaryl-coenzyme A reductase (HMGCR) to mimic the effects of statin therapy was associated with a reduced CRC risk (OR = 0.69, 95% CI: 0.49-0.99, p = 0.046). This study supports a causal relationship between higher levels of TC with CRC risk, and a further rationale for implementing public health strategies to reduce the prevalence of hyperlipidaemia.
Assuntos
Neoplasias Colorretais/genética , Predisposição Genética para Doença/genética , Hiperlipidemias/genética , Análise da Randomização Mendeliana/métodos , Polimorfismo de Nucleotídeo Único , Colesterol/sangue , Neoplasias Colorretais/sangue , Estudo de Associação Genômica Ampla/métodos , Estudo de Associação Genômica Ampla/estatística & dados numéricos , Humanos , Hiperlipidemias/sangue , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Modelos Logísticos , Razão de Chances , Medição de Risco , Fatores de Risco , Triglicerídeos/sangueRESUMO
BACKGROUND & AIMS: We analyzed data from twins to determine how much the familial risk of colorectal cancer can be attributed to genetic factors vs environment. We also examined whether heritability is distinct for colon vs rectal cancer, given evidence of distinct etiologies. METHODS: Our data set included 39,990 monozygotic and 61,443 same-sex dizygotic twins from the Nordic Twin Study of Cancer. We compared each cancer's risk in twins of affected co-twins relative to the cohort risk (familial risk ratio [FRR]). We then estimated the proportion of variation in risk that could be attributed to genetic factors (heritability). RESULTS: From earliest registration in 1943 through 2010, there were 1861 individuals diagnosed with colon cancer and 1268 diagnosed with rectal cancer. Monozygotic twins of affected co-twins had an FRR for colorectal cancer of 3.1 (95% confidence interval [CI], 2.4-3.8) relative to the cohort risk. Dizygotic twins of affected co-twins had an FRR for colorectal cancer of 2.2 (95% CI, 1.7-2.7). We estimated that 40% (95% CI, 33%-48%) of the variation in colorectal cancer risk could be attributed to genetic factors; unique environment only accounted for the remaining liability. For colon cancer, the FRR was 3.3 (95% CI, 2.1-4.5) for monozygotic twins and 2.6 (95% CI, 1.7-3.5) for dizygotic twins. For rectal cancer, comparable estimates were 3.3 (95% CI, 1.5-5.1) for monozygotic twins and 2.6 (95% CI, 1.2-4.0) for dizygotic twins. Heritability estimates for colon and rectal cancer were 16% (95% CI, 0-46%) and 15% (95% CI, 0-50%), common environment estimates were 15% (95% CI, 0-38%) and 11% (95% CI, 0-38%), and unique environment estimates were 68% (95% CI, 57%-79%) and 75% (95% CI, 61%-88%), respectively. CONCLUSIONS: Interindividual genetic differences could account for 40% of the variation in susceptibility to colorectal cancer; risk for colon and rectal cancers might have less of a genetic component than risk for colorectal cancer. Siblings, and particularly monozygotic co-twins, of individuals with colon or rectal cancer should consider personalized screening.
Assuntos
Neoplasias do Colo/epidemiologia , Neoplasias do Colo/genética , Saúde da Família , Predisposição Genética para Doença , Neoplasias Retais/epidemiologia , Neoplasias Retais/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Europa (Continente)/epidemiologia , Feminino , Humanos , Individualidade , Lactente , Masculino , Pessoa de Meia-Idade , Medição de Risco , Gêmeos Dizigóticos , Gêmeos Monozigóticos , Adulto JovemRESUMO
Genome-wide association studies have identified several germline single nucleotide polymorphisms (SNPs) significantly associated with colorectal cancer (CRC) incidence. Common germline genetic variation may also be related to CRC survival. We used a discovery-based approach to identify SNPs related to survival outcomes after CRC diagnosis. Genome-wide genotyping arrays were conducted for 3494 individuals with invasive CRC enrolled in six prospective cohort studies (median study-specific follow-up = 4.2-8.1 years). In pooled analyses, we used Cox regression to assess SNP-specific associations with CRC-specific and overall survival, with additional analyses stratified by stage at diagnosis. Top findings were followed-up in independent studies. A P value threshold of P < 5×10(-8) in analyses combining discovery and follow-up studies was required for genome-wide significance. Among individuals with distant-metastatic CRC, several SNPs at 6p12.1, nearest the ELOVL5 gene, were statistically significantly associated with poorer survival, with the strongest associations noted for rs209489 [hazard ratio (HR) = 1.8, P = 7.6×10(-10) and HR = 1.8, P = 3.7×10(-9) for CRC-specific and overall survival, respectively). No SNPs were statistically significantly associated with survival among all cases combined or in cases without distant-metastases. SNPs in 6p12.1/ELOVL5 were associated with survival outcomes in individuals with distant-metastatic CRC, and merit further follow-up for functional significance. Findings from this genome-wide association study highlight the potential importance of genetic variation in CRC prognosis and provide clues to genomic regions of potential interest.
Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Neoplasias Colorretais/diagnóstico , Feminino , Variação Genética , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos ProspectivosRESUMO
It is unclear whether dyslipidemia is associated with risk of colorectal neoplasia. The incidence of both conditions is increasing in Asia, motivating a number of new studies from this region. We performed a systematic literature search of Asian colonoscopy-based studies that collected blood lipid concentrations at the time of endoscopy. Persons found to have colorectal adenoma were considered cases, and those found to be adenoma-free were considered controls. Seventeen studies published between 2000 and 2014 met inclusion criteria, collectively enrolling 17,387 cases and 30,427 controls. Mean differences and adjusted odds ratios were summarized with random-effects meta-analyses. Compared with controls, cases had higher total cholesterol (mean difference (MD) = 2.4 mg/dL, 95% confidence interval (CI): 0.2, 4.6), higher low-density lipoprotein cholesterol (MD = 1.3 mg/dL, 95% CI: 0.1, 2.6), higher triglyceride (MD = 16.4 mg/dL, 95% CI: 11.2, 21.5), and lower high-density lipoprotein (HDL) cholesterol (MD = -2.1 mg/dL, 95% CI: -2.7, -1.6) concentrations. Based on adjusted odds ratios, associations for 40-mg/dL-higher triglyceride levels (odds ratio = 1.13, 95% CI: 1.05, 1.21) and 10-mg/dL-higher HDL cholesterol levels (odds ratio = 0.96, 95% CI: 0.92, 1.00) achieved statistical significance. Persons with adenoma were more likely to have unfavorable cholesterol profiles at the time of colonoscopy than those without adenoma. The most convincing evidence for an association between dyslipidemia and colorectal neoplasia was observed for hypertriglyceridemia.
Assuntos
Adenoma/epidemiologia , HDL-Colesterol/sangue , Colonoscopia/estatística & dados numéricos , Neoplasias Colorretais/epidemiologia , Dislipidemias/epidemiologia , Triglicerídeos/sangue , Adenoma/sangue , Ásia/epidemiologia , Neoplasias Colorretais/sangue , Comorbidade , Dislipidemias/sangue , Humanos , Incidência , PrevalênciaRESUMO
PURPOSE: Studies linking cholesterol levels to the development of colorectal neoplasia are inconsistent, and Mendelian randomization has been suggested as a way to help avoid problems with confounding and reverse causation. METHODS: We genotyped individuals who received a colonoscopy at Group Health (1998-2007) for 96 of 102 single-nucleotide polymorphisms identified by the Global Lipids Genetics Consortium. Participants included 139 advanced adenoma cases, 518 non-advanced adenoma cases, 380 non-adenomatous polyp cases, and 754 polyp-free controls. All had at least one available pre-colonoscopy lipid measurement from electronic records maintained by Group Health. RESULTS: Advanced adenoma cases were more likely than controls to have higher pre-colonoscopy zenith low-density lipoprotein (LDL), triglycerides (TG), and total cholesterol (TC) (odds ratio, OR per 20 mg/dL LDL increase: 1.16, 95 % confidence interval, CI 1.03-1.30; per 40 mg/dL TG increase: 1.09, 1.03-1.16; and per 20 mg/dL TC increase: 1.09, 1.02-1.18). For these traits, genotype-polyp ORs using weighted allele scores were not statistically significant (OR per increase in score scaled to a 20 mg/dL LDL increase: 1.17, 0.78-1.75; a 40 mg/dL TG increase: 1.12, 0.91-1.38; a 20 mg/dL TC increase: 0.99, 0.71-1.38). CONCLUSIONS: Cholesterol levels may be associated with advanced adenomas, but larger studies are warranted to determine whether this association can be attributed to genetics.
Assuntos
Adenoma/sangue , Colesterol/sangue , Pólipos do Colo/sangue , Pólipos do Colo/etiologia , Neoplasias Colorretais/sangue , Polimorfismo de Nucleotídeo Único , Triglicerídeos/sangue , Adenoma/etiologia , Adulto , Idoso , Biópsia , Pólipos do Colo/genética , Colonoscopia , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/genética , Feminino , Genótipo , Humanos , Lipídeos , Masculino , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Razão de Chances , FenótipoRESUMO
BACKGROUND: The National Birth Defects Prevention Study (NBDPS) contains a wealth of information on affected and unaffected family triads, and thus provides numerous opportunities to study gene-environment interactions (G×E) in the etiology of birth defect outcomes. Depending on the research objective, several analytic options exist to estimate G×E effects that use varying combinations of individuals drawn from available triads. METHODS: In this study, we discuss important considerations in the collection of genetic data and environmental exposures. RESULTS: We will also present several population- and family-based approaches that can be applied to data from the NBDPS including case-control, case-only, family-based trio, and maternal versus fetal effects. For each, we describe the data requirements, applicable statistical methods, advantages, and disadvantages. CONCLUSION: A range of approaches can be used to evaluate potentially important G×E effects in the NBDPS. Investigators should be aware of the limitations inherent to each approach when choosing a study design and interpreting results.
Assuntos
Anormalidades Congênitas/etiologia , Interação Gene-Ambiente , Predisposição Genética para Doença , Modelos Estatísticos , Projetos de Pesquisa , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Linhagem , Polimorfismo de Nucleotídeo Único , Fatores de RiscoRESUMO
Although use of non-steroidal anti-inflammatory drugs (NSAIDs) generally decreases colorectal cancer (CRC) risk, inherited genetic variation in inflammatory pathways may alter their potential as preventive agents. We investigated whether variation in prostaglandin synthesis and related pathways influences CRC risk in the Colon Cancer Family Registry by examining associations between 192 single nucleotide polymorphisms (SNPs) and two variable nucleotide tandem repeats (VNTRs) within 17 candidate genes and CRC risk. We further assessed interactions between these polymorphisms and NSAID use on CRC risk. Using a case-unaffected-sibling-control design, this study included 1621 primary invasive CRC cases and 2592 sibling controls among Caucasian men and women aged 18-90. After adjustment for multiple comparisons, two intronic SNPs were associated with rectal cancer risk: rs11571364 in ALOX12 [OR(het/hzv) = 1.87, 95% confidence interval (CI) = 1.19-2.95, P = 0.03] and rs45525634 in PTGER2 (OR(het/hzv) = 0.49, 95% CI = 0.29-0.82, P = 0.03). Additionally, there was an interaction between NSAID use and the intronic SNP rs2920421 in ALOX12 on risk of CRC (P = 0.03); among those with heterozygous genotypes, risk was reduced for current NSAID users compared with never or former users (OR(het) = 0.60, 95% CI = 0.45-0.80), though not among those with homozygous wild-type or variant genotypes. The results of this study suggest that genetic variation in ALOX12 and PTGER2 may affect the risk of rectal cancer. In addition, this study suggests plausible interactions between NSAID use and variants in ALOX12 on CRC risk. These results may aid in the development of genetically targeted cancer prevention strategies with NSAIDs.
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Anticarcinógenos/administração & dosagem , Vias Biossintéticas/genética , Neoplasias Colorretais/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Estudos de Casos e Controles , Neoplasias Colorretais/prevenção & controle , Feminino , Frequência do Gene , Genes Neoplásicos , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Prostaglandinas/biossíntese , Sistema de Registros , Fatores de RiscoRESUMO
We conducted a case-control study of the association between subsets of colorectal polyps, including adenomas and serrated polyps, and single-nucleotide polymorphisms (SNPs) related to colorectal cancer through prior genome-wide association studies (GWAS). Participants were enrollees in the Group Health Cooperative (Seattle, Washington) aged 24-79 years who received a colonoscopy from 1998 to 2007, donated a buccal or blood sample, and completed a structured questionnaire. We performed genotyping of 13 colorectal cancer susceptibility SNPs. Polytomous logistic regression models were used to estimate odds ratios and 95% confidence intervals for associations between polyps and the colorectal cancer risk allele for each SNP under a log-additive model. Analyses included 781 controls, 489 cases with adenoma, 401 cases with serrated polyps, and 188 cases with both polyp types. The following SNPs were associated with advanced adenomas: rs10936599, rs10795668, rs16892766, and rs9929218 (P < 0.05). For nonadvanced adenomas and for serrated polyps overall, only rs961253 was statistically significant (P < 0.05). These associations were in the same directions as those in prior colorectal cancer GWAS. No SNP was significantly associated with hyperplastic polyps, and only rs6983267 was significantly associated with sessile serrated polyps, but this association was opposite of that found in colorectal cancer GWAS. Our results suggest that the association between colorectal cancer susceptibility SNPs and colorectal polyps varies by polyp type.
Assuntos
Adenoma/genética , Pólipos do Colo/genética , Neoplasias Colorretais/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Adenoma/patologia , Adulto , Idoso , Estudos de Casos e Controles , Pólipos do Colo/classificação , Pólipos do Colo/patologia , Neoplasias Colorretais/patologia , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e QuestionáriosAssuntos
Colecalciferol , Vitamina D , Suplementos Nutricionais , Humanos , Intervalo Livre de Progressão , VitaminasRESUMO
Using a case-control design, we evaluated differences in risk factors for colorectal polyps according to histological type, anatomical site, and severity. Participants were enrollees in the Group Health Cooperative aged 20-79 years who underwent colonoscopy in Seattle, Washington, between 1998 and 2007 and comprised 628 adenoma cases, 594 serrated polyp cases, 247 cases with both types of polyps, and 1,037 polyp-free controls. Participants completed a structured interview, and polyps were evaluated via standardized pathology review. We used multivariable polytomous logistic regression to compare case groups with controls and with the other case groups. Factors for which the strength of the association varied significantly between adenomas and serrated polyps were sex (P < 0.001), use of estrogen-only postmenopausal hormone therapy (P = 0.01), and smoking status (P < 0.001). For lesion severity, prior endoscopy (P < 0.001) and age (P = 0.05) had significantly stronger associations with advanced adenomas than with nonadvanced adenomas; and higher education was positively correlated with sessile serrated polyps but not with other serrated polyps (P = 0.02). Statistically significant, site-specific associations were observed for current cigarette smoking (P = 0.05 among adenomas and P < 0.001 among serrated polyps), postmenopausal estrogen-only therapy (P = 0.01 among adenomas), and obesity (P = 0.01 among serrated polyps). These findings further illustrate the epidemiologic heterogeneity of colorectal neoplasia and may help elucidate carcinogenic mechanisms for distinct pathways.
Assuntos
Adenoma/epidemiologia , Adenoma/patologia , Pólipos do Colo/epidemiologia , Pólipos do Colo/patologia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Adulto , Idoso , Anti-Inflamatórios não Esteroides/administração & dosagem , Índice de Massa Corporal , Estudos de Casos e Controles , Colonoscopia , Terapia de Reposição de Estrogênios/estatística & dados numéricos , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Fatores de Risco , Índice de Gravidade de Doença , Sexo , Fumar/epidemiologia , Fatores SocioeconômicosRESUMO
OBJECTIVES: Colonoscopy is associated with a decreased risk of colorectal cancer but may be more effective in reducing the risk of distal than proximal malignancies. To gain insight into the differences between proximal and distal colon endoscopic performance, we conducted a case-control study of advanced adenomas, the primary targets of colorectal endoscopy screening, and sessile serrated polyps (SSPs), newly recognized precursor lesions for a colorectal cancer subset that occurs most often in the proximal colon. METHODS: The Group Health-based study population included 213 advanced adenoma cases, 172 SSP cases, and 1,704 controls aged 50-79 years, who received an index colonoscopy from 1998-2007. All participants completed a structured questionnaire covering endoscopy history. Participants with polyps underwent a standard pathology review to confirm the diagnosis and reclassify a subset as advanced adenomas or SSPs. Logistic regression analyses were conducted to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) for the association between endoscopy and advanced adenomas and SSPs separately; site-specific analyses were completed. RESULTS: Previous endoscopy was inversely associated with advanced adenomas in both the rectum/distal colon (OR=0.38; 95% CI: 0.26-0.56) and proximal colon (OR=0.31; 95% CI: 0.19-0.52), but there was no statistically significant association between previous endoscopy and SSPs (OR=0.80; 95%CI: 0.56-1.13). CONCLUSIONS: Our results support the hypothesis that the effect of endoscopy differs between advanced adenomas and SSPs. This may have implications for proximal colon cancer prevention and be due to the failure of endoscopy to detect/remove SSPs, or the hypothesized rapid development of SSPs.
Assuntos
Adenoma/diagnóstico , Neoplasias do Colo/diagnóstico , Pólipos do Colo/diagnóstico , Colonoscopia , Adenoma/patologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Neoplasias do Colo/patologia , Pólipos do Colo/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: This study examined prospective data from the Third National Health and Nutrition Examination Survey (NHANES III) cohort to investigate the relationship between cadmium exposure and cancer mortality, and the specific cancers associated with cadmium exposure, in the general population. METHODS: Vital status and cause of death through 31 December 2006 were obtained by the National Center for Health Statistics for NHANES III participants. The cadmium concentration of spot urine samples was measured and corrected for urine creatinine (uCd). Weighted Cox proportional hazards regression with age as the time metric was applied to estimate sex-specific adjusted HRs (aHRs) of mortality associated with uCd for all cancers and the cancers responsible for the most deaths in the USA. Estimates were stratified by smoking history and adjusted for education, body mass index and race. RESULTS: uCd was associated with cancer mortality (aHR per twofold higher uCd (95% CI), men: 1.26 (1.07 to 1.48); women: 1.21 (1.04 to 1.42)). In men, mortality from lung cancer, pancreatic cancer and non-Hodgkin lymphoma was associated with uCd; an association with leukaemia mortality was suggested. In women, associations were suggested with mortality due to lung cancer, leukaemia, ovarian and uterine cancer, but evidence was weaker than in men. CONCLUSIONS: Cadmium appears to be associated with overall cancer mortality in men and women, but the specific cancers associated differ between men and women, suggesting avenues for future research. Limitations of the study include the possibility of uncontrolled confounding by cigarette smoking or other factors, and the limited number of deaths due to some cancers.
Assuntos
Cádmio/efeitos adversos , Exposição Ambiental/efeitos adversos , Metais Pesados/efeitos adversos , Neoplasias/mortalidade , Adolescente , Adulto , Cádmio/urina , Causas de Morte , Creatinina/urina , Feminino , Humanos , Leucemia/induzido quimicamente , Leucemia/mortalidade , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/mortalidade , Linfoma não Hodgkin/induzido quimicamente , Linfoma não Hodgkin/mortalidade , Masculino , Metais Pesados/urina , Neoplasias/induzido quimicamente , Inquéritos Nutricionais , Neoplasias Pancreáticas/induzido quimicamente , Neoplasias Pancreáticas/mortalidade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores Sexuais , Fumar , Estados Unidos/epidemiologiaRESUMO
Common single nucleotide polymorphisms (SNPs) in SMAD7 (18q21) have been linked to colorectal cancer (CRC) risk in genome-wide association studies, but little is known about their effects on survival. SMAD7 regulates gastrointestinal inflammation by inhibiting transforming growth factor-ß (TGFB), which can act as both a tumor suppressor and a promoter of metastasis. Regular use of cyclooxygenase-2 (COX2) inhibitors, such as nonsteroidal anti-inflammatory drugs (NSAIDs), reduces the risk of developing CRC. Because COX2 overexpression reduces the growth suppressing effects of TGFB, we hypothesized that survival may depend on both SMAD7 genotype and prediagnostic NSAID use. Postmenopausal women, ages 50-74, diagnosed with incident invasive CRC from 1997 to 2002 were identified using the Seattle-Puget Sound Surveillance, Epidemiology, and End Results (SEER) cancer registry. Information on prediagnostic NSAID use and other risk factors was ascertained by interview, and women were followed-up for survival through December 31, 2009. Seven hundred and twenty-seven cases were genotyped for two GWAS hits in SMAD7 with minor allele frequency > 30%, one with minor allele associated with decreased risk (rs4939827) and one with minor allele associated with increased risk (rs4464148). Two hundred and forty-two deaths occurred, 160 attributable to CRC. Among those without distant disease at diagnosis, CRC-specific survival differed by genotype only for NSAID users: each minor allele of rs4939827 was associated with worse survival [hazard ratio (HR) = 2.67, 95% confidence interval (CI): 1.33-5.37] and each minor allele of rs4464148 was associated with better survival (HR = 0.41, CI 0.18-0.94). SMAD7 variants known to be important for CRC risk were associated with disease-specific survival among prediagnostic NSAID users.
Assuntos
Adenocarcinoma/genética , Adenocarcinoma/prevenção & controle , Anti-Inflamatórios não Esteroides/administração & dosagem , Neoplasias Colorretais/genética , Neoplasias Colorretais/prevenção & controle , Proteína Smad7/genética , Idoso , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Feminino , Estudo de Associação Genômica Ampla , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Pós-Menopausa/genética , Estudos ProspectivosRESUMO
Several new statistical methods have been developed to identify the overall impact of an exposure mixture on health outcomes. Weighted quantile sum (WQS) regression assigns the joint mixture effect weights to indicate the overall association of multiple exposures, and quantile-based g-computation is a generalized version of WQS without the restriction of directional homogeneity. This paper proposes an adaptive-mixture-categorization (AMC)-based g-computation approach that combines g-computation with an optimal exposure categorization search using the F statistic. AMC-based g-computation reduces variance within each category and retains the variance between categories to build more powerful predictors. In a simulation study, the performance of association analysis was improved using categorizing by AMC compared with quantiles. We applied this method to assess the association between a mixture of 12 trace element concentrations measured from toenails and the risk of non-muscle invasive bladder cancer. Our findings suggested that medium-level (116.7-145.5 µg/g) vs. low-level (39.5-116.2 µg/g) of toenail zinc had a statistically significant positive association with bladder cancer risk.
Assuntos
Oligoelementos , Neoplasias da Bexiga Urinária , Humanos , Oligoelementos/análise , Exposição Ambiental/análise , Neoplasias da Bexiga Urinária/epidemiologia , Neoplasias da Bexiga Urinária/etiologia , Zinco/análise , Projetos de Pesquisa , Teorema de BayesRESUMO
BACKGROUND: Sex hormones have been implicated in the etiology of colorectal neoplasia in women for over 40 years, but there has been very little investigation of the role of these hormones in men. METHODS: Using data from an adenoma chemoprevention trial, we conducted a secondary analysis to examine serum hormone levels [testosterone, androstenedione, DHEA sulfate (DHEAS), and sex hormone binding globulin (SHBG)] and risk of colorectal precursors in 925 men. Multivariable logistic regression models were fit to evaluate adjusted associations between hormone levels and risk of "low-risk" (single tubular adenoma < 1 cm) and "high-risk" lesions (advanced adenoma or sessile serrated adenoma or right-sided serrated polyp or >2 adenomas of any size). RESULTS: Overall, levels of free testosterone, total testosterone, androstenedione, DHEAS, or SHBG were not associated with either "low-risk" or "high-risk" early precursor lesions in the colorectum. CONCLUSIONS: These findings do not support the role of sex hormones in early colorectal neoplasia among men. IMPACT: This large prospective study address a missing gap in knowledge by providing information on the role of sex hormones in colorectal neoplasia in males.