RESUMO
BACKGROUND: Pancreatic cancer presents as advanced disease in >80% of patients; yet, appropriate ages to consider prevention and early detection strategies are poorly defined. We investigated age-specific associations and attributable risks of pancreatic cancer for established modifiable and non-modifiable risk factors. PATIENTS AND METHODS: We included 167 483 participants from two prospective US cohort studies with 1190 incident cases of pancreatic cancer during >30 years of follow-up; 5107 pancreatic cancer cases and 8845 control participants of European ancestry from a completed multicenter genome-wide association study (GWAS); and 248 893 pancreatic cancer cases documented in the US Surveillance, Epidemiology, and End Results (SEER) Program. Across different age categories, we investigated cigarette smoking, obesity, diabetes, height, and non-O blood group in the prospective cohorts; weighted polygenic risk score of 22 previously identified single nucleotide polymorphisms in the GWAS; and male sex and black race in the SEER Program. RESULTS: In the prospective cohorts, all five risk factors were more strongly associated with pancreatic cancer risk among younger participants, with associations attenuated among those aged >70 years. The hazard ratios comparing participants with three to five risk factors with those with no risk factors were 9.24 [95% confidence interval (CI) 4.11-20.77] among those aged ≤60 years, 3.00 (95% CI 1.85-4.86) among those aged 61-70 years, and 1.46 (95% CI 1.10-1.94) among those aged >70 years (Pheterogeneity = 3×10-5). These factors together were related to 65.6%, 49.7%, and 17.2% of incident pancreatic cancers in these age groups, respectively. In the GWAS and the SEER Program, the associations with the polygenic risk score, male sex, and black race were all stronger among younger individuals (Pheterogeneity ≤0.01). CONCLUSIONS: Established risk factors are more strongly associated with earlier-onset pancreatic cancer, emphasizing the importance of age at initiation for cancer prevention and control programs targeting this highly lethal malignancy.
Assuntos
Estudo de Associação Genômica Ampla , Neoplasias Pancreáticas , Humanos , Masculino , Neoplasias Pancreáticas/etiologia , Neoplasias Pancreáticas/genética , Estudos Prospectivos , Fatores de Risco , Neoplasias PancreáticasRESUMO
BACKGROUND: Regular use of aspirin has been associated with a reduced risk of cancer at several sites but the data for endometrial cancer are conflicting. Evidence regarding use of other analgesics is limited. PATIENTS AND METHODS: We pooled individual-level data from seven cohort and five case-control studies participating in the Epidemiology of Endometrial Cancer Consortium including 7120 women with endometrial cancer and 16 069 controls. For overall analyses, study-specific odds ratios (ORs) and 95% confidence intervals (CI) were estimated using logistic regression and combined using random-effects meta-analysis; for stratified analyses, we used mixed-effects logistic regression with study as a random effect. RESULTS: At least weekly use of aspirin and non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with an approximately 15% reduced risk of endometrial cancer among both overweight and obese women (OR = 0.86 [95% CI 0.76-0.98] and 0.86 [95% CI 0.76-0.97], respectively, for aspirin; 0.87 [95% CI 0.76-1.00] and 0.84 [0.74-0.96], respectively, for non-aspirin NSAIDs). There was no association among women of normal weight (body mass index < 25 kg/m2, Pheterogeneity = 0.04 for aspirin, Pheterogeneity = 0.003 for NSAIDs). Among overweight and obese women, the inverse association with aspirin was stronger for use 2-6 times/week (OR = 0.81, 95% CI 0.68-0.96) than for daily use (0.91, 0.80-1.03), possibly because a high proportion of daily users use low-dose formulations. There was no clear association with use of acetaminophen. CONCLUSION: Our pooled analysis provides further evidence that use of standard-dose aspirin or other NSAIDs may reduce risk of endometrial cancer among overweight and obese women.
Assuntos
Acetaminofen/efeitos adversos , Analgésicos não Narcóticos/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Aspirina/efeitos adversos , Neoplasias do Endométrio/epidemiologia , Estudos de Casos e Controles , Estudos de Coortes , Neoplasias do Endométrio/induzido quimicamente , Feminino , Seguimentos , Humanos , Prognóstico , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Observational studies have reported a modest association between obesity and risk of ovarian cancer; however, whether it is also associated with survival and whether this association varies for the different histologic subtypes are not clear. We undertook an international collaborative analysis to assess the association between body mass index (BMI), assessed shortly before diagnosis, progression-free survival (PFS), ovarian cancer-specific survival and overall survival (OS) among women with invasive ovarian cancer. METHODS: We used original data from 21 studies, which included 12 390 women with ovarian carcinoma. We combined study-specific adjusted hazard ratios (HRs) using random-effects models to estimate pooled HRs (pHR). We further explored associations by histologic subtype. RESULTS: Overall, 6715 (54%) deaths occurred during follow-up. A significant OS disadvantage was observed for women who were obese (BMI: 30-34.9, pHR: 1.10 (95% confidence intervals (CIs): 0.99-1.23); BMI: ⩾35, pHR: 1.12 (95% CI: 1.01-1.25)). Results were similar for PFS and ovarian cancer-specific survival. In analyses stratified by histologic subtype, associations were strongest for women with low-grade serous (pHR: 1.12 per 5 kg m(-2)) and endometrioid subtypes (pHR: 1.08 per 5 kg m(-2)), and more modest for the high-grade serous (pHR: 1.04 per 5 kg m(-2)) subtype, but only the association with high-grade serous cancers was significant. CONCLUSIONS: Higher BMI is associated with adverse survival among the majority of women with ovarian cancer.
Assuntos
Neoplasias Epiteliais e Glandulares/patologia , Obesidade/patologia , Neoplasias Ovarianas/patologia , Índice de Massa Corporal , Carcinoma Epitelial do Ovário , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Epiteliais e Glandulares/mortalidade , Obesidade/mortalidade , Neoplasias Ovarianas/mortalidadeRESUMO
PURPOSE OF INVESTIGATION: Ovarian cancer is associated with poor prognosis and altered protein expression patterns may be useful for identifying patients likely to have poor disease outcomes. The impact of altered INPP4B protein expression on prognosis is unclear. The aim of this study was to evaluate the implication of INPP4B expression changes in a large series of ovarian cancer tissue samples. MATERIALS AND METHODS: Tissue microarrays were constructed from 599 epithelial ovarian tumors and stained with antibodies for INPP4B, p53, and PTEN. Proportional hazard models were used to estimate survival hazard ratios (HRs) associated with altered protein expression. RESULTS: Seventy-nine percent of the ovarian cancers demonstrated loss of INPP4B, whereas 53% showed aberrant p53 expression (i.e., complete loss of p53 or over-expression of p53) and 8% showed loss of PTEN. INPP4B was frequently lost in serous and endometrioid cancer subtypes, aberrant p53 expression was most common among serous subtype, and loss of PTEN was most common among endometrioid tumors (p for all three proteins across histologic subtypes ≤ 0.0001). INPP4B loss or aberrant p53 expression were both associated with increased mortality (HR = 1.84; 95% CI 1.27 - 2.68 and HR = 3.10; 95% CI 2.33 - 4.11, respectively); however, in multivariate models, only the relationship with p53 achieved statistical significance (HR = 1.20; 95% CI 0.82 - 1.76 for INPP4B and HR = 1.73; 95% CI 1.28 - 2.34 for p53). Conclusion: The INPP4B protein is frequently lost in serous and endometrioid subtypes of ovarian cancer. A possible prognostic role of INPP4B for endometrioid ovarian tumors requires further evaluation.
Assuntos
Adenocarcinoma de Células Claras/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Endometrioide/metabolismo , Neoplasias Císticas, Mucinosas e Serosas/metabolismo , Neoplasias Epiteliais e Glandulares/metabolismo , Neoplasias Ovarianas/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Monoéster Fosfórico Hidrolases/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Adenocarcinoma de Células Claras/mortalidade , Adenocarcinoma de Células Claras/patologia , Adulto , Idoso , Carcinoma Endometrioide/mortalidade , Carcinoma Endometrioide/patologia , Carcinoma Epitelial do Ovário , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Císticas, Mucinosas e Serosas/mortalidade , Neoplasias Císticas, Mucinosas e Serosas/patologia , Neoplasias Epiteliais e Glandulares/mortalidade , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Prognóstico , Modelos de Riscos Proporcionais , Adulto JovemRESUMO
BACKGROUND: The potential role of vitamin D in the aetiology of pancreatic cancer is unclear, with recent studies suggesting both positive and negative associations. PATIENTS AND METHODS: We used data from nine case-control studies from the International Pancreatic Cancer Case-Control Consortium (PanC4) to examine associations between pancreatic cancer risk and dietary vitamin D intake. Study-specific odds ratios (ORs) were estimated using multivariable logistic regression, and ORs were then pooled using a random-effects model. From a subset of four studies, we also calculated pooled estimates of association for supplementary and total vitamin D intake. RESULTS: Risk of pancreatic cancer increased with dietary intake of vitamin D [per 100 international units (IU)/day: OR = 1.13, 95% confidence interval (CI) 1.07-1.19, P = 7.4 × 10(-6), P-heterogeneity = 0.52; ≥230 versus <110 IU/day: OR = 1.31, 95% CI 1.10-1.55, P = 2.4 × 10(-3), P-heterogeneity = 0.81], with the association possibly stronger in people with low retinol/vitamin A intake. CONCLUSION: Increased risk of pancreatic cancer was observed with higher levels of dietary vitamin D intake. Additional studies are required to determine whether or not our finding has a causal basis.
Assuntos
Adenocarcinoma/epidemiologia , Neoplasias Pancreáticas/induzido quimicamente , Vitamina D/administração & dosagem , Vitamina D/efeitos adversos , Vitaminas/administração & dosagem , Vitaminas/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Diabetes Mellitus/epidemiologia , Dieta/estatística & dados numéricos , Suplementos Nutricionais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Obesidade/epidemiologia , Razão de Chances , Neoplasias Pancreáticas/epidemiologia , Pancreatite/epidemiologia , Fatores de RiscoRESUMO
BACKGROUND: Flavonoids, polyphenolic compounds concentrated in fruits and vegetables, have experimentally demonstrated chemopreventive effects against oesophageal and gastric cancer. Few epidemiologic studies have examined flavonoid intake and incidence of these cancers, and none have considered survival. METHODS: In this USA multicentre population-based study, case participants (diagnosed during 1993-1995 with oesophageal adenocarcinoma (OEA, n=274), gastric cardia adenocarcinoma (GCA, n=248), oesophageal squamous cell carcinoma (OES, n=191), and other gastric adenocarcinoma (OGA, n=341)) and frequency-matched controls (n=662) were interviewed. Food frequency questionnaire responses were linked with USDA Flavonoid Databases and available literature for six flavonoid classes and lignans. Case participants were followed until 2000 for vital status. Multivariable-adjusted odds ratios (ORs) and hazard ratios (HRs) (95% confidence intervals (CIs)) were estimated, comparing highest with lowest intake quartiles, using polytomous logistic and proportional hazards regressions, respectively. RESULTS: Little or no consistent association was found for total flavonoid intake (main population sources: black tea, orange/grapefruit juice, and wine) and incidence or survival for any tumour type. Intake of anthocyanidins, common in wine and fruit juice, was associated with a 57% reduction in the risk of incident OEA (OR=0.43, 95% CI=0.29-0.66) and OES (OR=0.43, 95% CI=0.26-0.70). The ORs for isoflavones, for which coffee was the main source, were increased for all tumours, except OES. Anthocyanidins were associated with decreased risk of mortality for GCA (HR=0.63, 95% CI=0.42-0.95) and modestly for OEA (HR=0.87, 95% CI=0.60-1.26), but CIs were wide. CONCLUSIONS: Our findings, if confirmed, suggest that increased dietary anthocyanidin intake may reduce incidence and improve survival for these cancers.
Assuntos
Dieta/estatística & dados numéricos , Neoplasias Esofágicas/epidemiologia , Flavonoides/administração & dosagem , Neoplasias Gástricas/epidemiologia , Estudos de Casos e Controles , Feminino , Frutas , Humanos , Incidência , Masculino , Fatores de Risco , Análise de Sobrevida , Estados Unidos , VerdurasRESUMO
BACKGROUND: Nulliparity is an endometrial cancer risk factor, but whether or not this association is due to infertility is unclear. Although there are many underlying infertility causes, few studies have assessed risk relations by specific causes. METHODS: We conducted a pooled analysis of 8153 cases and 11 713 controls from 2 cohort and 12 case-control studies. All studies provided self-reported infertility and its causes, except for one study that relied on data from national registries. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Nulliparous women had an elevated endometrial cancer risk compared with parous women, even after adjusting for infertility (OR=1.76; 95% CI: 1.59-1.94). Women who reported infertility had an increased risk compared with those without infertility concerns, even after adjusting for nulliparity (OR=1.22; 95% CI: 1.13-1.33). Among women who reported infertility, none of the individual infertility causes were substantially related to endometrial cancer. CONCLUSIONS: Based on mainly self-reported infertility data that used study-specific definitions of infertility, nulliparity and infertility appeared to independently contribute to endometrial cancer risk. Understanding residual endometrial cancer risk related to infertility, its causes and its treatments may benefit from large studies involving detailed data on various infertility parameters.
Assuntos
Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/etiologia , Infertilidade Feminina/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Paridade , Fatores de Risco , AutorrelatoRESUMO
PURPOSE OF INVESTIGATION: Microsatellite instability (MSI) is a hallmark of defective mismatch repair and is present in approximately 20% of ovarian cancers. It is not known if the presence of MSI predicts survival in women with epithelial ovarian cancer. MATERIALS AND METHODS: Cases of epithelial ovarian cancer were ascertained from a population-based study in Ontario and tumour samples were tested for MSI, using five MSI markers. Patients were divided into MSI-high and MSI-low/normal, according to National Cancer Institute criteria. The authors compared the prevalence of specific prognostic factors in the two subgroups, including age, grade, stage, and histology. They estimated the hazard ratio for death from ovarian cancer associated with MSI-high and with other prognostic factors using a multi-variate analysis. RESULTS: A total of 418 ovarian cancer patients were included. One hundred and twenty-seven (19.7%) cancers were MSI- high. Subgroup analyses did not reveal any statistically significant differences for pathologic features associated with MSI status. No survival difference was seen according to MSI status. CONCLUSIONS: The presence of MSI in ovarian cancer is not associated with survival.
Assuntos
Instabilidade de Microssatélites , Neoplasias Ovarianas/genética , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Modelos de Riscos ProporcionaisRESUMO
Genetic testing for BRCA1 and BRCA2 gene mutations, in conjunction with preventive salpingo-oophorectomy for mutation carriers, may be used to prevent a proportion of invasive ovarian cancers ('personalized medicine'). We evaluated the potential utility of this approach at a population level by reviewing the pedigree information and genetic test results from 1342 ovarian cancer patients in Ontario. Of the 1342 patients tested, 176 patients had a BRCA1 or BRCA2 mutation; of these, 48 women would have qualified for testing prior to the development of cancer based on the eligibility criteria in place for the province of Ontario. In summary, 48 of 1342 unselected cases of ovarian cancer (3.6%) might have been prevented if genetic testing criteria were universally applied to all women in Ontario at risk for ovarian cancer.
Assuntos
Testes Genéticos/métodos , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/prevenção & controle , Adulto , Idoso , Feminino , Genes BRCA1 , Genes BRCA2 , Predisposição Genética para Doença , Genética Populacional , Humanos , Pessoa de Meia-Idade , Mutação , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Peptic ulcer and its treatments have been associated to pancreatic cancer risk, although the evidence is inconsistent. METHODS: We pooled 10 case-control studies within the Pancreatic Cancer Case-control Consortium (PanC4), including 4717 pancreatic cancer cases and 9374 controls, and estimated summary odds ratios (OR) using multivariable logistic regression models. RESULTS: The OR for pancreatic cancer was 1.10 [95% confidence interval (CI) 0.98-1.23] for history of ulcer (OR = 1.08 for gastric and 0.97 for duodenal ulcer). The association was stronger for a diagnosis within 2 years before cancer diagnosis (OR = 2.43 for peptic, 1.75 for gastric, and 1.98 for duodenal ulcer). The OR was 1.53 (95% CI 1.15-2.03) for history of gastrectomy; however, the excess risk was limited to a gastrectomy within 2 years before cancer diagnosis (OR = 6.18, 95% CI 1.82-20.96), while no significant increased risk was observed for longer time since gastrectomy. No associations were observed for pharmacological treatments for ulcer, such as antacids, H2-receptor antagonists, or proton-pump inhibitors. CONCLUSIONS: This uniquely large collaborative study does not support the hypothesis that peptic ulcer and its treatment materially affect pancreatic cancer risk. The increased risk for short-term history of ulcer and gastrectomy suggests that any such association is due to increased cancer surveillance.
Assuntos
Gastroenteropatias/patologia , Neoplasias Pancreáticas/patologia , Úlcera/patologia , Idoso , Estudos de Casos e Controles , Feminino , Gastrectomia/efeitos adversos , Gastroenteropatias/complicações , Gastroenteropatias/epidemiologia , Gastroenteropatias/cirurgia , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/epidemiologia , Fatores de Risco , Úlcera/complicações , Úlcera/epidemiologia , Úlcera/cirurgiaRESUMO
BACKGROUND: Limited epidemiological studies show inverse associations between dietary flavonoid intake and pancreatic cancer risk, but results are inconsistent and are based on few cases. We examined the association between intake of flavonoids and pancreatic cancer risk in the large, prospective National Institutes of Health-AARP Diet and Health Study Cohort. METHODS: During follow-up through 2006 (median follow-up 10.6 years), 2379 pancreatic cancer cases were identified. We used Cox proportional hazards modelling to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: We found no association between total flavonoid intake (Q5 vs Q1 HR=1.09, 95% CI: 0.96-1.24) or any flavonoid subtypes and pancreatic cancer risk. Significant interactions were not observed by age, sex, smoking status, BMI or diabetes. CONCLUSION: Our results do not support the hypothesis that flavonoids have a protective role in pancreatic cancer carcinogenesis.
Assuntos
Dieta , Flavonoides/administração & dosagem , Neoplasias Pancreáticas/epidemiologia , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Mutations in genes for hereditary non-polyposis colorectal cancer (HNPCC) in ovarian cancer patients remains poorly defined. We sought to estimate the frequency and characteristics of HNPCC gene mutations in a population-based sample of women with epithelial ovarian cancer. METHODS: The analysis included 1893 women with epithelial ovarian cancer ascertained from three population-based studies. Full-germline DNA sequencing of the coding regions was performed on three HNPCC genes, MLH1, MSH2 and MSH6. Collection of demographic, clinical and family history information was attempted in all women. RESULTS: Nine clearly pathogenic mutations were identified, including five in MSH6, two each in MLH1 and MSH2. In addition, 28 unique predicted pathogenic missense variants were identified in 55 patients. Pathogenic mutation carriers had an earlier mean age at diagnosis of ovarian cancer, overrepresentation of cancers with non-serous histologies and a higher number of relatives with HNPCC-related cancers. CONCLUSIONS: Our findings suggest that fewer than 1% of women with ovarian cancer harbour a germline mutation in the HNPCC genes, with overrepresentation of MSH6 mutations. This represents a lower-range estimate due to the large number of predicted pathogenic variants in which pathogenicity could not definitively be determined. Identification of mismatch repair gene mutations has the potential to impact screening and treatment decisions in these women.
Assuntos
Reparo de Erro de Pareamento de DNA , Mutação , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Ovarianas/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Carcinoma Epitelial do Ovário , Neoplasias Colorretais/genética , Neoplasias Colorretais Hereditárias sem Polipose/genética , Proteínas de Ligação a DNA/genética , Feminino , Humanos , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL , Proteína 2 Homóloga a MutS/genética , Proteínas Nucleares/genéticaRESUMO
BACKGROUND: Pancreatitis is a known risk factor for pancreatic cancer; however, an unknown fraction of the disease is thought to be a consequence of tumor-related duct obstruction. PATIENTS AND METHODS: A pooled analysis of a history of pancreatitis and risk of pancreatic cancer was carried out considering the time interval between diagnoses and potential modification by covariates. Adjusted pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from 10 case-control studies (5048 cases of ductal pancreatic adenocarcinoma and 10,947 controls) taking part in the International Pancreatic Cancer Case-Control Consortium (PanC4). RESULTS: The association between pancreatitis and pancreatic cancer was nearly three-fold at intervals of >2 years between diagnoses (OR: 2.71, 95% CI: 1.96-3.74) and much stronger at intervals of ≤2 years (OR: 13.56, 95% CI: 8.72-21.90) probably reflecting a combination of reverse causation and antecedent misdiagnosis of pancreas cancer as pancreatitis. The younger (<65 years) pancreatic cancer cases showed stronger associations with previous (>2 years) pancreatitis (OR: 3.91, 95% CI: 2.53-6.04) than the older (≥65 years) cases (OR: 1.68, 95% CI: 1.02-2.76; P value for interaction: 0.006). CONCLUSIONS: Despite a moderately strong association between pancreatitis (diagnosed before >2 years) and pancreatic cancer, the population attributable fraction was estimated at 1.34% (95% CI: 0.612-2.07%), suggesting that a relatively small proportion of pancreatic cancer might be avoided if pancreatitis could be prevented.
Assuntos
Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/etiologia , Pancreatite/complicações , Adenocarcinoma/epidemiologia , Adenocarcinoma/etiologia , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Estudos de Casos e Controles , Complicações do Diabetes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pancreatite/etiologia , Fatores de Risco , Fumar/efeitos adversosRESUMO
BACKGROUND: To evaluate the dose-response relationship between cigarette smoking and pancreatic cancer and to examine the effects of temporal variables. METHODS: We analyzed data from 12 case-control studies within the International Pancreatic Cancer Case-Control Consortium (PanC4), including 6507 pancreatic cases and 12 890 controls. We estimated summary odds ratios (ORs) by pooling study-specific ORs using random-effects models. RESULTS: Compared with never smokers, the OR was 1.2 (95% confidence interval [CI] 1.0-1.3) for former smokers and 2.2 (95% CI 1.7-2.8) for current cigarette smokers, with a significant increasing trend in risk with increasing number of cigarettes among current smokers (OR=3.4 for ≥35 cigarettes per day, P for trend<0.0001). Risk increased in relation to duration of cigarette smoking up to 40 years of smoking (OR=2.4). No trend in risk was observed for age at starting cigarette smoking, whereas risk decreased with increasing time since cigarette cessation, the OR being 0.98 after 20 years. CONCLUSIONS: This uniquely large pooled analysis confirms that current cigarette smoking is associated with a twofold increased risk of pancreatic cancer and that the risk increases with the number of cigarettes smoked and duration of smoking. Risk of pancreatic cancer reaches the level of never smokers â¼20 years after quitting.
Assuntos
Neoplasias Pancreáticas/etiologia , Fumar/efeitos adversos , Estudos de Casos e Controles , Humanos , Modelos Logísticos , Análise Multivariada , Razão de Chances , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Cigarette smoking is the best-characterized risk factor for pancreatic cancer. However, data are limited for other tobacco smoking products and smokeless tobacco. MATERIALS AND METHODS: We conducted a pooled analysis of cigar and pipe smoking and smokeless tobacco use and risk of pancreatic cancer using data from 11 case-control studies (6056 cases and 11,338 controls) within the International Pancreatic Cancer Case-Control Consortium (PanC4). Pooled odds ratios (OR) and the corresponding 95% confidence intervals (CI) were estimated by unconditional multiple logistic regression models adjusted for study center and selected covariates. RESULTS: Compared with never tobacco users, the OR for cigar-only smokers was 1.6 (95% CI: 1.2-2.3), i.e. comparable to that of cigarette-only smokers (OR 1.5; 95% CI 1.4-1.6). The OR was 1.1 (95% CI 0.69-1.6) for pipe-only smokers. There was some evidence of increasing risk with increasing amount of cigar smoked per day (OR 1.82 for ≥ 10 grams of tobacco), although not with duration. The OR for ever smokeless tobacco users as compared with never tobacco users was 0.98 (95% CI 0.75-1.3). CONCLUSION: This collaborative analysis provides evidence that cigar smoking is associated with an excess risk of pancreatic cancer, while no significant association emerged for pipe smoking and smokeless tobacco use.
Assuntos
Neoplasias Pancreáticas/etiologia , Fumar/efeitos adversos , Tabaco sem Fumaça/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Risco , TabagismoRESUMO
Multiple genetic loci confer susceptibility to breast and ovarian cancers. We have previously developed a model (BOADICEA) under which susceptibility to breast cancer is explained by mutations in BRCA1 and BRCA2, as well as by the joint multiplicative effects of many genes (polygenic component). We have now updated BOADICEA using additional family data from two UK population-based studies of breast cancer and family data from BRCA1 and BRCA2 carriers identified by 22 population-based studies of breast or ovarian cancer. The combined data set includes 2785 families (301 BRCA1 positive and 236 BRCA2 positive). Incidences were smoothed using locally weighted regression techniques to avoid large variations between adjacent intervals. A birth cohort effect on the cancer risks was implemented, whereby each individual was assumed to develop cancer according to calendar period-specific incidences. The fitted model predicts that the average breast cancer risks in carriers increase in more recent birth cohorts. For example, the average cumulative breast cancer risk to age 70 years among BRCA1 carriers is 50% for women born in 1920-1929 and 58% among women born after 1950. The model was further extended to take into account the risks of male breast, prostate and pancreatic cancer, and to allow for the risk of multiple cancers. BOADICEA can be used to predict carrier probabilities and cancer risks to individuals with any family history, and has been implemented in a user-friendly Web-based program (http://www.srl.cam.ac.uk/genepi/boadicea/boadicea_home.html).
Assuntos
Neoplasias da Mama/genética , Genes BRCA1 , Genes BRCA2 , Predisposição Genética para Doença , Mutação , Neoplasias Ovarianas/genética , Adulto , Fatores Etários , Idoso , Neoplasias da Mama/etiologia , Feminino , Triagem de Portadores Genéticos , Humanos , Pessoa de Meia-Idade , Modelos Genéticos , Segunda Neoplasia Primária/etiologia , Segunda Neoplasia Primária/genética , Neoplasias Ovarianas/etiologiaRESUMO
There is evidence that progesterone plays a role in the aetiology of invasive epithelial ovarian cancer. Therefore, genes involved in pathways that regulate progesterone may be candidates for susceptibility to this disease. Previous studies have suggested that genetic variants in the progesterone receptor gene (PGR) may be associated with ovarian cancer risk, although results have been inconsistent. We have established an international consortium to pool resources and data from many ovarian cancer case-control studies in an effort to identify variants that influence risk. In this study, three PGR single nucleotide polymorphisms (SNPs), for which previous data have suggested they affect ovarian cancer risk, were examined. These were +331 C/T (rs10895068), PROGINS (rs1042838), and a 3' variant (rs608995). A total of 4788 ovarian cancer cases and 7614 controls from 12 case-control studies were included in this analysis. Unconditional logistic regression was used to model the association between each SNP and ovarian cancer risk and two-sided P-values are reported. Overall, risk of ovarian cancer was not associated with any of the three variants studied. However, in histopathological subtype analyses, we found a statistically significant association between risk of endometrioid ovarian cancer and the PROGINS allele (n=651, OR=1.17, 95% CI=1.01-1.36, P=0.036). We also observed borderline evidence of an association between risk of endometrioid ovarian cancer and the +331C/T variant (n=725 cases; OR=0.80, 95% CI 0.62-1.04, P=0.100). These data suggest that while these three variants in the PGR are not associated with ovarian cancer overall, the PROGINS variant may play a modest role in risk of endometrioid ovarian cancer.
Assuntos
Carcinoma Endometrioide/genética , Predisposição Genética para Doença , Neoplasias Ovarianas/genética , Polimorfismo de Nucleotídeo Único , Receptores de Progesterona/genética , Adulto , Idoso , Carcinoma Endometrioide/patologia , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Mutagênese Insercional , Invasividade Neoplásica , Neoplasias Ovarianas/classificação , Neoplasias Ovarianas/patologia , Fatores de RiscoRESUMO
OBJECTIVE: Members of the glutathione S-transferase (GST) family have been shown to have functional polymorphisms that may affect drug metabolism and influence the effects of chemotherapy and survival from cancer. GSTM1, GSTT1, and GSTP1 genotypes were evaluated for their role in ovarian cancer treatment and survival. METHODS: DNA was extracted from tumor tissues of 215 patients diagnosed with primary epithelial ovarian cancer. GSTM1 and GSTT1 genotypes were determined by multiplex PCR; GSTP1 genotypes were assessed with PCR-RFLP. Associations between GST polymorphisms and risk of ovarian cancer progression or death were analyzed using Cox proportional hazards regression; subgroups of patients receiving different chemotherapeutics were also evaluated. RESULTS: GST polymorphisms were not found to be associated with patient or tumor characteristics or response to treatment. However, GSTM1 null patients were less likely to have disease progression (HR: 0.65, 95% CI: 0.43-0.99) or to die (HR: 0.68, 95% CI: 0.45-1.03) compared to patients with GSTM1. Patients with GSTM1 null and GSTP1 ile/val or val/val (reduced function) had a further reduction in risk of disease progression compared to patients with GSTM1 or GSTP1 ile/ile (HR: 0.42, 95% CI: 0.24-0.75). A similar association was also suggested for overall survival (HR: 0.61, 95% CI: 0.36-1.05). Subgroup analyses indicated that the effects of GST on survival were more pronounced among patients treated with specific chemotherapeutics. CONCLUSION: These findings support the idea that reduced GST function may improve ovarian cancer survival after post-operative chemotherapy; evaluation of GST functional polymorphisms may help to predict ovarian cancer prognosis.