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1.
Cancer Res ; 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31932455

RESUMO

Repeated exposure to the acute pro-inflammatory environment that follows ovulation at the ovarian surface and distal fallopian tube over a woman's reproductive years may increase ovarian cancer risk. To address this, analyses included individual-level data from 558,709 naturally menopausal women across 20 prospective cohorts, among whom 3,246 developed invasive epithelial ovarian cancer (2045 serous, 319 endometrioid, 184 mucinous, 121 clear cell, 577 other/unknown). Cox models were used to estimate multivariable-adjusted hazard ratios (HR) between lifetime ovulatory cycles (LOC) and its components and ovarian cancer risk overall and by histotype. Women in the 90th percentile of LOC (>514 cycles) were almost twice as likely to be diagnosed with ovarian cancer than women in the 10th percentile (<294) [HR (95% confidence interval): 1.92 (1.60-2.30)]. Risk increased 14% per five-year increase in LOC (60 cycles) [(1.10-1.17)]; this association remained after adjustment for LOC components: number of pregnancies and oral contraceptive use [1.08 (1.04-1.12)]. The association varied by histotype, with increased risk of serous [1.13 (1.09-1.17)], endometrioid [1.20 (1.10-1.32)], and clear cell [1.37 (1.18-1.58)], but not mucinous [0.99 (0.88-1.10), P-heterogeneity=0.01] tumors. Heterogeneity across histotypes was reduced [P-heterogeneity=0.15] with adjustment for LOC components [1.08 serous, 1.11 endometrioid, 1.26 clear cell, 0.94 mucinous]. Although the 10-year absolute risk of ovarian cancer is small, it roughly doubles as the number of LOC rises from ~300 to 500. The consistency and linearity of effects strongly support the hypothesis that each ovulation leads to small increases in the risk of most ovarian cancers, a risk which cumulates through life, suggesting this as an important area for identifying intervention strategies.

2.
J Natl Cancer Inst ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31917448

RESUMO

BACKGROUND: Although 20 pancreatic cancer susceptibility loci have been identified through genome-wide association studies (GWAS) in individuals of European ancestry, much of its heritability remains unexplained and the genes responsible largely unknown. METHODS: To discover novel pancreatic cancer risk loci and possible causal genes, we performed a pancreatic cancer transcriptome-wide association study (TWAS) in Europeans using three approaches, FUSION, MetaXcan and SMulTiXcan. We integrated GWAS summary statistics from 9,040 pancreatic cancer cases and 12,496 controls, with gene expression prediction models built using transcriptome data from histologically normal pancreatic tissue samples (NCI Laboratory of Translational Genomics, LTG (n = 95) and Genotype-Tissue Expression, GTEx v7 (n = 174) datasets), and data from 48 different tissues (GTEx v7, n = 74-421 samples). RESULTS: We identified 25 genes whose genetically predicted expression was statistically significantly associated with pancreatic cancer risk (FDR < 0.05), including 14 candidate genes at 11 novel loci (1p36.12: CELA3B; 9q31.1: SMC2, SMC2-AS1; 10q23.31: RP11-80H5.9; 12q13.13: SMUG1; 14q32.33: BTBD6; 15q23: HEXA; 15q26.1: RCCD1; 17q12:, PNMT, CDK12, PGAP3; 17q22: SUPT4H1; 18q11.22: RP11-888D10.3; and 19p13.11: PGPEP1) and 11 at 6 known risk loci (5p15.33: TERT, CLPTM1L, ZDHHC11B; 7p14.1: INHBA; 9q34.2: ABO; 13q12.2: PDX1; 13q22.1: KLF5; and 16q23.1: WDR59, CFDP1, BCAR1, TMEM170A). The association for 12 of these genes (CELA3B, SMC2, and PNMT at novel risk loci, and TERT, CLPTM1L, INHBA, ABO, PDX1, KLF5, WDR59, CFDP1 and BCAR1 at known loci) remained statistically significant after Bonferroni correction. CONCLUSIONS: By integrating gene expression and genotype data, we identified novel pancreatic cancer risk loci and candidate functional genes that warrant further investigation.

3.
Cancer Res ; 79(20): 5442-5451, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31462430

RESUMO

Growing epidemiologic evidence supports chronic inflammation as a mechanism of ovarian carcinogenesis. An association between a circulating marker of inflammation, C-reactive protein (CRP), and ovarian cancer risk has been consistently observed, yet, potential heterogeneity of this association by tumor and patient characteristics has not been adequately explored. In this study, we pooled data from case-control studies nested within six cohorts in the Ovarian Cancer Cohort Consortium (OC3) to examine the association between CRP and epithelial ovarian cancer risk overall, by histologic subtype and by participant characteristics. CRP concentrations were measured from prediagnosis serum or plasma in 1,091 cases and 1,951 controls. Multivariable conditional logistic regression was used to estimate ORs and 95% confidence intervals (CI). When CRP was evaluated using tertiles, no associations with ovarian cancer risk were observed. A 67% increased ovarian cancer risk was found for women with CRP concentrations >10 mg/L compared with <1 mg/L (OR = 1.67; 95% CI = 1.12-2.48). A CRP concentration >10 mg/L was positively associated with risk of mucinous (OR = 9.67; 95% CI = 1.10-84.80) and endometrioid carcinoma (OR = 3.41; 95% CI = 1.07-10.92), and suggestively positive, although not statistically significant, for serous (OR = 1.43; 95% CI = 0.82-2.49) and clear cell carcinoma (OR = 2.05; 95% CI = 0.36-11.57; P heterogeneity = 0.20). Heterogeneity was observed with oral contraceptive use (P interaction = 0.03), where the increased risk was present only among ever users (OR = 3.24; 95% CI = 1.62-6.47). This study adds to the existing evidence that CRP plays a role in ovarian carcinogenesis and suggests that inflammation may be particularly implicated in the etiology of endometrioid and mucinous carcinoma. SIGNIFICANCE: C-reactive protein is involved in ovarian carcinogenesis, and chronic inflammation may be particularly implicated in the etiology of mucinous and endometrioid carcinomas.

4.
Am J Epidemiol ; 188(9): 1, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31318018
5.
Cancer Res ; 79(15): 3973-3982, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31113819

RESUMO

Biliary tract cancers are rare but highly fatal with poorly understood etiology. Identifying potentially modifiable risk factors for these cancers is essential for prevention. Here we estimated the relationship between adiposity and cancer across the biliary tract, including cancers of the gallbladder (GBC), intrahepatic bile ducts (IHBDC), extrahepatic bile ducts (EHBDC), and the ampulla of Vater (AVC). We pooled data from 27 prospective cohorts with over 2.7 million adults. Adiposity was measured using baseline body mass index (BMI), waist circumference, hip circumference, waist-to-hip, and waist-to-height ratios. HRs and 95% confidence intervals (95% CI) were estimated using Cox proportional hazards models adjusted for sex, education, race, smoking, and alcohol consumption with age as the time metric and the baseline hazard stratified by study. During 37,883,648 person-years of follow-up, 1,343 GBC cases, 1,194 EHBDC cases, 784 IHBDC cases, and 623 AVC cases occurred. For each 5 kg/m2 increase in BMI, there were risk increases for GBC (HR = 1.27; 95% CI, 1.19-1.36), IHBDC (HR = 1.32; 95% CI, 1.21-1.45), and EHBDC (HR = 1.13; 95% CI, 1.03-1.23), but not AVC (HR = 0.99; 95% CI, 0.88-1.11). Increasing waist circumference, hip circumference, waist-to-hip ratio, and waist-to-height ratio were associated with GBC and IHBDC but not EHBDC or AVC. These results indicate that adult adiposity is associated with an increased risk of biliary tract cancer, particularly GBC and IHBDC. Moreover, they provide evidence for recommending weight maintenance programs to reduce the risk of developing these cancers. SIGNIFICANCE: These findings identify a correlation between adiposity and biliary tract cancers, indicating that weight management programs may help minimize the risk of these diseases.

6.
J Natl Cancer Inst ; 111(12): 1263-1278, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31127946

RESUMO

BACKGROUND: Tobacco and alcohol are well-established risk factors for numerous cancers, yet their relationship to biliary tract cancers remains unclear. METHODS: We pooled data from 26 prospective studies to evaluate associations of cigarette smoking and alcohol consumption with biliary tract cancer risk. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for associations with smoking and alcohol consumption were calculated. Random-effects meta-analysis produced summary estimates. All statistical tests were two-sided. RESULTS: Over a period of 38 369 156 person-years of follow-up, 1391 gallbladder, 758 intrahepatic bile duct, 1208 extrahepatic bile duct, and 623 ampulla of Vater cancer cases were identified. Ever, former, and current smoking were associated with increased extrahepatic bile duct and ampulla of Vater cancers risk (eg, current vs never smokers HR = 1.69, 95% CI = 1.34 to 2.13 and 2.22, 95% CI = 1.69 to 2.92, respectively), with dose-response effects for smoking pack-years, duration, and intensity (all Ptrend < .01). Current smoking and smoking intensity were also associated with intrahepatic bile duct cancer (eg, >40 cigarettes per day vs never smokers HR = 2.15, 95 % CI = 1.15 to 4.00; Ptrend = .001). No convincing association was observed between smoking and gallbladder cancer. Alcohol consumption was only associated with intrahepatic bile duct cancer, with increased risk for individuals consuming five or more vs zero drinks per day (HR = 2.35, 95%CI = 1.46 to 3.78; Ptrend = .04). There was evidence of statistical heterogeneity among several cancer sites, particularly between gallbladder cancer and the other biliary tract cancers. CONCLUSIONS: Smoking appears to increase the risk of developing all biliary tract cancers except gallbladder cancer. Alcohol may increase the risk of intrahepatic bile duct cancer. Findings highlight etiologic heterogeneity across the biliary tract.

7.
Lancet Public Health ; 4(2): e97-e106, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30655229

RESUMO

BACKGROUND: Increasing premature mortality among some groups of Americans has been largely driven by increases in drug poisoning deaths. However, to our knowledge, a formal descriptive study by race and ethnicity, socioeconomic status, rurality, and geography has not been done. In this study, we examined US trends in premature all-cause and drug poisoning mortality between 2000 and 2015 at the county level among white, black, and Latino people. METHODS: We used US mortality data for the period Jan 1, 2000, to Dec 31, 2015, including underlying cause of death and demographic data, collected from death certificates by the Centers for Disease Control and Prevention National Center for Health Statistics, and ascertained county attributes from the 2011-15 Census American Community Survey. We categorised counties into quintiles on the basis of the percentage of people unemployed, the percentage of people with a bachelor's degree, median income, and rurality. We estimated premature (ie, deaths in those aged 25-64 years) age-standardised mortality for all causes (by race and ethnicity) and drug poisoning, by county, for the periods of 2000-03 and 2012-15. We estimated annual percentage changes in mortality (2000-15) by county-level characteristics. FINDINGS: Premature mortality declined from 2000-03 to 2012-15 among black and Latino people, but increased among white people in many US counties. Drug poisoning mortality increased in counties throughout the country. Significant increases between 2000 and 2015 occurred across low and high socioeconomic status and urban and rural counties among white people aged 25-64 years (annual percentage change range 4·56% per year [95% CI 3·56-5·57] to 11·51% per year [9·41-13·65]), black people aged 50-64 years (2·27% per year [0·42-4·16] to 9·46% per year [7·02-11·96]), Latino women aged 25-49 years (2·43% per year [1·18-3·71] to 5·01% per year [3·80-6·23]), and Latino men aged 50-64 years (2·42% per year [0·53-4·34] to 5·96% per year [3·86-8·11]). Although drug poisoning mortality increased rapidly in counties with the lowest socioeconomic status and in rural counties, most deaths during 2012-15 occurred in the largest metropolitan counties (121 395 [76%] in metropolitan counties with ≥250 000 people vs 2175 [1%] in the most rural counties), reflecting population size. INTERPRETATION: Premature mortality has declined among black and Latino people in the USA, and increased among white people, particularly in less affluent and rural counties. Increasing drug poisoning mortality was not limited to poor white people in rural areas. Rapid increases have occurred in communities throughout the USA regardless of race and ethnicity, socioeconomic status, or rurality. Widespread public health interventions are needed to addess this public health emergency. FUNDING: National Institutes of Health.

8.
J Natl Cancer Inst ; 111(2): 137-145, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29860330

RESUMO

BACKGROUND: Aspirin use is associated with reduced risk of several cancers. A pooled analysis of 12 case-control studies showed a 10% decrease in ovarian cancer risk with regular aspirin use, which was stronger for daily and low-dose users. To prospectively investigate associations of analgesic use with ovarian cancer, we analyzed data from 13 studies in the Ovarian Cancer Cohort Consortium (OC3). METHODS: The current study included 758 829 women who at study enrollment self-reported analgesic use, among whom 3514 developed ovarian cancer. Using Cox regression, we assessed associations between frequent medication use and risk of ovarian cancer. Dose and duration were also evaluated. All statistical tests were two-sided. RESULTS: Women who used aspirin almost daily (≥6 days/wk) vs infrequent/nonuse experienced a 10% reduction in ovarian cancer risk (rate ratio [RR] = 0.90, 95% confidence interval [CI] = 0.82 to 1.00, P = .05). Frequent use (≥4 days/wk) of aspirin (RR = 0.95, 95% CI = 0.88 to 1.03), nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs; RR = 1.00, 95% CI = 0.90 to 1.11), or acetaminophen (RR = 1.05, 95% CI = 0.88 to 1.24) was not associated with risk. Daily acetaminophen use (RR = 1.28, 95% CI = 1.00 to 1.65, P = .05) was associated with elevated ovarian cancer risk. Risk estimates for frequent, long-term (10+ years) use of aspirin (RR = 1.15, 95% CI = 0.98 to 1.34) or nonaspirin NSAIDs (RR = 1.19, 95% CI = 0.84 to 1.68) were modestly elevated, although not statistically significantly so. CONCLUSIONS: This large, prospective analysis suggests that women who use aspirin daily have a slightly lower risk of developing ovarian cancer (∼10% lower than infrequent/nonuse)-similar to the risk reduction observed in case-control analyses. The observed potential elevated risks for 10+ years of frequent aspirin and NSAID use require further study but could be due to confounding by medical indications for use or variation in drug dosing.

9.
J Natl Cancer Inst ; 111(2): 129-136, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29790947

RESUMO

BACKGROUND: Pelvic inflammatory disease (PID) has been associated with ovarian cancer risk. To clarify the role of Chlamydia trachomatis and other infectious agents in the development of ovarian cancer, we evaluated the association of serologic markers with incident ovarian cancer using a staged approach in two independent populations. METHODS: Studies included: 1) a case-control study in Poland (244 ovarian cancers/556 control subjects) and 2) a prospective nested case-control study in the PLCO Cancer Screening Trial (160 ovarian cancers/159 control subjects). Associations of serologic marker levels with ovarian cancer risk at diagnostic as well as higher thresholds, identified in Poland and independently evaluated in PLCO, were estimated using multivariable adjusted logistic regression. RESULTS: In the Polish study, antibodies (based on laboratory cut-point) against the chlamydia plasmid-encoded Pgp3 protein (serological gold standard) were associated with increased ovarian cancer risk (adjusted odds ratio [OR] = 1.63, 95% confidence interval [CI] = 1.20 to 2.22); when a positive result was redefined at higher levels, ovarian cancer risk was increased (cut-point 2: OR = 2.00, 95% CI = 1.38 to 2.89; cut-point 3 [max OR]: OR = 2.19, 95% CI = 1.29 to 3.73). In the prospective PLCO study, Pgp3 antibodies were associated with elevated risk at the laboratory cut-point (OR = 1.43, 95% CI = 0.78 to 2.63) and more stringent cut-points (cut-point 2: OR = 2.25, 95% CI = 1.07 to 4.71); cut-point 3: OR = 2.53, 95% CI = 0.63 to 10.08). In both studies, antibodies against other infectious agents measured were not associated with risk. CONCLUSIONS: In two independent populations, antibodies against prior/current C. trachomatis (Pgp3) were associated with a doubling in ovarian cancer risk, whereas markers of other infectious agents were unrelated. These findings lend support for an association between PID and ovarian cancer.

10.
Am J Prev Med ; 56(1): 27-37, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30454906

RESUMO

INTRODUCTION: Worldwide, an estimated 189 million adults smoke tobacco "occasionally" but not every day. Yet few studies have examined the health risks of non-daily smoking. METHODS: Data from the 1991, 1992, and 1995 U.S. National Health Interview Surveys, a nationally representative sample of 70,913 U.S. adults (aged 18-95 years) were pooled. Hazard ratios and 95% CIs for death through 2011 were estimated from Cox proportional hazards regression using age as the underlying time metric and stratified by 5-year birth cohorts in 2017. RESULTS: Non-daily smokers reported smoking a median of 15 days and 50 cigarettes per month in contrast to daily smokers who smoked a median of 600 cigarettes per month. Compared with never smokers, lifelong nondaily smokers who had never smoked daily had a 72% higher mortality risk (95% CI=1.36, 2.18): higher risks were observed for cancer, heart disease, and respiratory disease mortalities. Higher mortality risks were observed among lifelong non-daily smokers who reported 11-30 (hazard ratio=1.34, 95% CI=0.81, 2.20); 31-60 (hazard ratio=2.02, 95% CI=1.17, 3.29); and >60 cigarettes per month (hazard ratio=1.74, 95% CI=1.12, 2.72) than never smokers. Median life-expectancy was about 5 years shorter for lifelong non-daily smokers than never smokers. As expected, daily smokers had even higher mortality risks (hazard ratio=2.50, 95% CI=2.35, 2.66) and shorter survival (10 years less). CONCLUSIONS: Although the mortality risks of non-daily smokers are lower than daily smokers, they are still substantial. Policies should be specifically directed at this growing group of smokers.

11.
Am J Epidemiol ; 188(2): 363-371, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30299454

RESUMO

Many smokers do not quit but instead reduce the number of cigarettes they smoke per day (CPD) over their lifetime. Yet the associations of such changes in CPD with health risks are unclear. We examined the association of changes in CPD with subsequent death in the period 2004-2011 among 253,947 participants of the National Institutes of Health-AARP Diet and Health Study. Using a questionnaire assessing responders' history of smoking cigarettes, we identified cigarette smokers who quit, decreased, maintained, or increased their CPD between ages 25-29 and 50-59 years. Hazard ratios and 95% confidence intervals were obtained from multivariable adjusted Cox proportional hazards regression models. Relative to never smokers, smokers who maintained a consistent CPD had 2.93 times (95% confidence interval (CI): 2.82, 3.05) higher all-cause mortality risk, and participants who increased their CPD had still higher risk (hazard ratio (HR) = 3.37, 95% CI: 3.23, 3.52). Death risk was lower among participants who decreased their CPD (HR = 2.38, 95% CI: 2.25, 2.52) or quit smoking (for quitting between ages 30 and 39 years, HR = 1.32, 95% CI: 1.25, 1.39). Similar patterns were observed for smoking-related causes of death, with particularly strong associations for lung cancer and respiratory disease. Reductions in CPD over the lifetime meaningfully decreased death risk; however, cessation provided a larger benefit than even large declines in CPD.


Assuntos
Fumar Cigarros/mortalidade , Produtos do Tabaco/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Fumar Cigarros/patologia , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Abandono do Hábito de Fumar/estatística & dados numéricos , Estados Unidos/epidemiologia
12.
Cancer Epidemiol Biomarkers Prev ; 28(1): 189-197, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30262599

RESUMO

BACKGROUND: Evidence suggests that inflammation increases risk for ovarian cancer. Aspirin has been shown to decrease ovarian cancer risk, though the mechanism is unknown. Studies of inflammatory markers, lipid molecules such as arachidonic acid, linoleic acid, and alpha-linoleic acid metabolites, and development of ovarian cancer are essential to understand the potential mechanisms. METHODS: We conducted a nested case-control study (157 cases/156 matched controls) within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Unconditional logistic regression was used to estimate the association between prediagnostic serum levels of 31 arachidonic acid/linoleic acid/alpha-linoleic acid metabolites and risk of ovarian cancer. RESULTS: Five of the 31 arachidonic acid/linoleic acid/alpha-linoleic acid (free fatty acids) metabolites were positively associated with ovarian cancer risk: 8-HETE [tertile 3 vs. 1: OR 2.53 (95% confidence interval [CI] 1.18-5.39), P trend 0.02], 12,13-DHOME [2.49 (1.29-4.81), 0.01], 13-HODE [2.47 (1.32-4.60), 0.005], 9-HODE [1.97 (1.06-3.68), 0.03], 9,12,13-THOME [2.25 (1.20-4.21), 0.01]. In analyses by subtype, heterogeneity was suggested for 8-HETE [serous OR (95% CI): 2.53 (1.18-5.39) vs. nonserous OR (95% CI): 1.15 (0.56-2.36), P het 0.1] and 12,13-EpOME [1.95 (0.90-4.22) vs. 0.82 (0.39-1.73), 0.05]. CONCLUSIONS: Women with increased levels of five fatty acid metabolites (8-HETE, 12,13-DHOME, 13-HODE, 9-HODE, and 9,12,13-THOME) were at increased risk of developing ovarian cancer in the ensuing decade. All five metabolites are derived from either arachidonic acid (8-HETE) or linoleic acid (12,13-DHOME, 13-HODE, 9-HODE, 9,12,13-THOME) via metabolism through the LOX/cytochrome P450 pathway. IMPACT: The identification of these risk-related fatty acid metabolites provides mechanistic insights into the etiology of ovarian cancer and indicates the direction for future research.

13.
Int J Cancer ; 145(1): 58-69, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30561796

RESUMO

Ovarian cancer risk factors differ by histotype; however, within subtype, there is substantial variability in outcomes. We hypothesized that risk factor profiles may influence tumor aggressiveness, defined by time between diagnosis and death, independent of histology. Among 1.3 million women from 21 prospective cohorts, 4,584 invasive epithelial ovarian cancers were identified and classified as highly aggressive (death in <1 year, n = 864), very aggressive (death in 1 to < 3 years, n = 1,390), moderately aggressive (death in 3 to < 5 years, n = 639), and less aggressive (lived 5+ years, n = 1,691). Using competing risks Cox proportional hazards regression, we assessed heterogeneity of associations by tumor aggressiveness for all cases and among serous and endometrioid/clear cell tumors. Associations between parity (phet = 0.01), family history of ovarian cancer (phet = 0.02), body mass index (BMI; phet ≤ 0.04) and smoking (phet < 0.01) and ovarian cancer risk differed by aggressiveness. A first/single pregnancy, relative to nulliparity, was inversely associated with highly aggressive disease (HR: 0.72; 95% CI [0.58-0.88]), no association was observed for subsequent pregnancies (per pregnancy, 0.97 [0.92-1.02]). In contrast, first and subsequent pregnancies were similarly associated with less aggressive disease (0.87 for both). Family history of ovarian cancer was only associated with risk of less aggressive disease (1.94 [1.47-2.55]). High BMI (≥35 vs. 20 to < 25 kg/m2 , 1.93 [1.46-2.56] and current smoking (vs. never, 1.30 [1.07-1.57]) were associated with increased risk of highly aggressive disease. Results were similar within histotypes. Ovarian cancer risk factors may be directly associated with subtypes defined by tumor aggressiveness, rather than through differential effects on histology. Studies to assess biological pathways are warranted.


Assuntos
Carcinoma Epitelial do Ovário/epidemiologia , Carcinoma Epitelial do Ovário/patologia , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/patologia , Idoso , Índice de Massa Corporal , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Paridade , Gravidez , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Fumar/epidemiologia
14.
Lancet Public Health ; 3(8): e374-e384, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30037721

RESUMO

BACKGROUND: Although life expectancy has been projected to increase across high-income countries, gains for the USA are anticipated to be among the smallest, and overall US death rates actually increased from 2014 to 2015, with divergence for specific US populations. Therefore, projecting future premature mortality is essential for clinical and public health service planning, curbing rapidly increasing causes of death, and sustaining progress in declining causes of death. We aimed to project premature mortality (here defined as deaths of individuals aged 25-64 years) trends through 2030, and to estimate the total number of projected deaths, the projected number of potential years of life lost due to premature mortality, and the effect of reducing projected accidental death rates by 2% per year. METHODS: We obtained death certificate data for the US population aged 25-64 years for 1990-2015 from the US Centers for Disease Control and Prevention (CDC) National Center for Health Statistics. We obtained US mortality data for 2016 for non-American Indian or Alaska native groups from CDC WONDER; data for 2016 were not available for American Indians or Alaska natives. Our analysis focused on all-cause premature mortality and the commonest causes of premature death (cancer, heart disease, accidents, suicide, and chronic liver disease or cirrhosis) among white, black, Hispanic, Asian or Pacific islanders, and American Indian or Alaska native men and women. We estimated age-standardised premature mortality and corresponding annual percentage changes for 2017-30 by sex and race or ethnic origin by use of age-period-cohort forecasting models. We also did a sensitivity analysis projecting future mortality from cross-sectional mortality and a JoinPoint of the (log) period rate ratio curve. We calculated absolute death counts by use of corresponding age-specific and year-specific US census population projections, and estimated years of potential life lost. FINDINGS: During 2017-30, all-cause deaths are projected to increase among white women and American Indians or Alaska natives, resulting in 239 700 excess premature deaths relative to 2017 rates (a 10% increase). Mortality declines in white men and black, Hispanic, and Asian or Pacific islander men and women will result in 945 900 fewer deaths (a 14% reduction). Cancer mortality rates are projected to decline among white, black, Hispanic, and Asian or Pacific islander women and men, with the largest declines among black women (age-standardised premature mortality rate 2016: 104·5 deaths per 100 000 woman-years; 2030: 77·1 per 100 000 woman-years) and men (2016: 116·8 per 100 000 man-years; 2030: 81·6 per 100 000 man-years). Heart disease death rates are projected to increase in American Indian or Alaska native men (2015: 150·9 per 100 000 man-years; 2030: 175·9 per 100 000 man-years) and decline in other groups, albeit only slightly in white (2016: 35·6 per 100 000 woman-years; 2030: 31·1 per 100 000 woman-years) and American Indian or Alaska native women (2015: 64·4 per 100 000 woman-years; 2030: 62·8 per 100 000 woman-years). Accidental death rates are projected to increase in all US populations except Asian or Pacific islander women, and will increase most rapidly among white women (2030: 60·5 per 100 000 woman-years) and men (2030: 101·9 per 100 000 man-years) and American Indian or Alaska native women (2030: 97·5 per 100 000 woman-years) and men (2030: 298·7 per 100 000 man-years). Suicide rates are projected to increase for all groups, and chronic liver disease and cirrhosis deaths are projected to increase for all groups except black men. A 2% per year reduction in projected accidental deaths would eliminate an estimated 178 700 deaths during 2017-30. INTERPRETATION: To reduce future premature mortality, effective interventions are needed to address rapidly rising mortality rates due to accidents, suicides, and chronic liver disease and cirrhosis. FUNDING: National Cancer Institute Intramural Research Program.


Assuntos
Mortalidade Prematura/tendências , Adulto , Grupos Étnicos/estatística & dados numéricos , Feminino , Previsões , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Mortalidade Prematura/etnologia , Estados Unidos/epidemiologia
15.
Int J Cancer ; 142(2): 271-280, 2018 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-28929489

RESUMO

An increasing proportion of US smokers smoke ≤10 cigarettes per day (CPD) or do not smoke every day, yet the health effects of low-intensity smoking are poorly understood. We identified lifelong smokers of <1 or 1-10 CPD and evaluated risk of incident cancer among 238,525 cancer-free adults, aged 59-82, in the NIH-AARP Diet and Health Study. A questionnaire administered in 2004-2005 assessed CPD during nine age-periods (<15 to ≥70). We estimated hazard ratios (HR) and 95% confidence intervals (CI) using multivariable-adjusted Cox proportional hazards regression with age as the underlying time metric. Of the 18,233 current smokers, (7.6%), 137 and 1,243 reported consistently smoking <1 CPD and 1-10 CPD, respectively. Relative to never smokers, current smokers who reported consistently smoking 1-10 CPD over their lifetime were 2.34 (95% CI = 1.86-2.93) times more likely to develop smoking-related cancer. Current lifetime smokers of <1 CPD were 1.89 (95% CI = 0.90-3.96) times more likely to develop tobacco-related cancer, although the association did not reach statistical significance. Associations were observed for lifelong smoking of ≤10 CPD with lung cancer (HR = 9.65, 95% CI = 6.93-13.43); bladder cancer (HR = 2.22, 95% CI = 1.22-4.05); and pancreatic cancer (HR = 2.03, 95%CI: 1.05-3.95). Among lifelong ≤10 CPD smokers, former smokers had lower risks of smoking-related cancer with longer time since cessation and longer smoking duration. Lifelong <1 and 1-10 CPD smokers are at increased risk of incident cancer relative to never smokers and would benefit from cessation, providing further evidence that even low-levels of cigarette smoking cause cancer.


Assuntos
Fumar Cigarros/efeitos adversos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pancreáticas/epidemiologia , Neoplasias da Bexiga Urinária/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Estudos de Coortes , Feminino , Seguimentos , Humanos , Incidência , Neoplasias Pulmonares/etiologia , Masculino , Pessoa de Meia-Idade , National Institutes of Health (U.S.) , Estadiamento de Neoplasias , Neoplasias Pancreáticas/etiologia , Prognóstico , Medição de Risco , Fatores de Tempo , Estados Unidos/epidemiologia , Neoplasias da Bexiga Urinária/etiologia , Adulto Jovem
16.
Lupus Sci Med ; 4(1): e000187, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29214033

RESUMO

Objective: Determinants of the increased risk of diffuse large B-cell lymphoma (DLBCL) in SLE are unclear. Using data from a recent lymphoma genome-wide association study (GWAS), we assessed whether certain lupus-related single nucleotide polymorphisms (SNPs) were also associated with DLBCL. Methods: GWAS data on European Caucasians from the International Lymphoma Epidemiology Consortium (InterLymph) provided a total of 3857 DLBCL cases and 7666 general-population controls. Data were pooled in a random-effects meta-analysis. Results: Among the 28 SLE-related SNPs investigated, the two most convincingly associated with risk of DLBCL included the CD40 SLE risk allele rs4810485 on chromosome 20q13 (OR per risk allele=1.09, 95% CI 1.02 to 1.16, p=0.0134), and the HLA SLE risk allele rs1270942 on chromosome 6p21.33 (OR per risk allele=1.17, 95% CI 1.01 to 1.36, p=0.0362). Of additional possible interest were rs2205960 and rs12537284. The rs2205960 SNP, related to a cytokine of the tumour necrosis factor superfamily TNFSF4, was associated with an OR per risk allele of 1.07, 95% CI 1.00 to 1.16, p=0.0549. The OR for the rs12537284 (chromosome 7q32, IRF5 gene) risk allele was 1.08, 95% CI 0.99 to 1.18, p=0.0765. Conclusions: These data suggest several plausible genetic links between DLBCL and SLE.

17.
Cancer Epidemiol Biomarkers Prev ; 26(4): 597-606, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28314823

RESUMO

Background: There are few established risk factors for gallbladder cancer beyond gallstones. Recent studies suggest a higher risk with high body mass index (BMI), an indicator of general heaviness, but evidence from other body size measures is lacking.Methods: Associations of adult BMI, young adult BMI, height, adult weight gain, waist circumference (WC), waist-height ratio (WHtR), hip circumference (HC), and waist-hip ratio (WHR) with gallbladder cancer risk were evaluated. Individual-level data from 1,878,801 participants in 19 prospective cohort studies (14 studies had circumference measures) were harmonized and included in this analysis. Multivariable Cox proportional hazards regression estimated hazard ratios (HR) and 95% confidence intervals (CI).Results: After enrollment, 567 gallbladder cancer cases were identified during 20.1 million person-years of observation, including 361 cases with WC measures. Higher adult BMI (per 5 kg/m2, HR: 1.24; 95% CI, 1.13-1.35), young adult BMI (per 5 kg/m2, HR: 1.12; 95% CI, 1.00-1.26), adult weight gain (per 5 kg, HR: 1.07; 95% CI, 1.02-1.12), height (per 5 cm, HR: 1.10; 95% CI, 1.03-1.17), WC (per 5 cm, HR: 1.09; 95% CI, 1.02-1.17), WHtR (per 0.1 unit, HR: 1.24; 95% CI, 1.00-1.54), and HC (per 5 cm, HR: 1.13; 95% CI, 1.04-1.22), but not WHR (per 0.1 unit, HR: 1.03; 95% CI, 0.87-1.22), were associated with higher risks of gallbladder cancer, and results did not differ meaningfully by sex or other demographic/lifestyle factors.Conclusions: These findings indicate that measures of overall and central excess body weight are associated with higher gallbladder cancer risks.Impact: Excess body weight is an important, and potentially preventable, gallbladder cancer risk factor. Cancer Epidemiol Biomarkers Prev; 26(4); 597-606. ©2017 AACR.


Assuntos
Índice de Massa Corporal , Tamanho Corporal , Neoplasias da Vesícula Biliar/epidemiologia , Circunferência da Cintura , Adulto , Feminino , Neoplasias da Vesícula Biliar/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/classificação , Obesidade/complicações , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Razão Cintura-Estatura , Relação Cintura-Quadril , Ganho de Peso , Adulto Jovem
18.
Lancet ; 389(10073): 1043-1054, 2017 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-28131493

RESUMO

BACKGROUND: Reduction of premature mortality is a UN Sustainable Development Goal. Unlike other high-income countries, age-adjusted mortality in the USA plateaued in 2010 and increased slightly in 2015, possibly because of rising premature mortality. We aimed to analyse trends in mortality in the USA between 1999 and 2014 in people aged 25-64 years by age group, sex, and race and ethnicity, and to identify specific causes of death underlying the temporal trends. METHODS: For this analysis, we used cause-of-death and demographic data from death certificates from the US National Center for Health Statistics, and population estimates from the US Census Bureau. We estimated annual percentage changes in mortality using age-period-cohort models. Age-standardised excess deaths were estimated for 2000 to 2014 as observed deaths minus expected deaths (estimated from 1999 mortality rates). FINDINGS: Between 1999 and 2014, premature mortality increased in white individuals and in American Indians and Alaska Natives. Increases were highest in women and those aged 25-30 years. Among 30-year-olds, annual mortality increases were 2·3% (95% CI 2·1-2·4) for white women, 0·6% (0·5-0·7) for white men, and 4·3% (3·5-5·0) and 1·9% (1·3-2·5), respectively, for American Indian and Alaska Native women and men. These increases were mainly attributable to accidental deaths (primarily drug poisonings), chronic liver disease and cirrhosis, and suicide. Among individuals aged 25-49 years, an estimated 111 000 excess premature deaths occurred in white individuals and 6600 in American Indians and Alaska Natives during 2000-14. By contrast, premature mortality decreased substantially across all age groups in Hispanic individuals (up to 3·2% per year), black individuals (up to 3·9% per year), and Asians and Pacific Islanders (up to 2·6% per year), mainly because of declines in HIV, cancer, and heart disease deaths, resulting in an estimated 112 000 fewer deaths in Hispanic individuals, 311 000 fewer deaths in black individuals, and 34 000 fewer deaths in Asians and Pacific Islanders aged 25-64 years. During 2011-14, American Indians and Alaska Natives had the highest premature mortality, followed by black individuals. INTERPRETATION: Important public health successes, including HIV treatment and smoking cessation, have contributed to declining premature mortality in Hispanic individuals, black individuals, and Asians and Pacific Islanders. However, this progress has largely been negated in young and middle-aged (25-49 years) white individuals, and American Indians and Alaska Natives, primarily because of potentially avoidable causes such as drug poisonings, suicide, and chronic liver disease and cirrhosis. The magnitude of annual mortality increases in the USA is extremely unusual in high-income countries, and a rapid public health response is needed to avert further premature deaths. FUNDING: US National Cancer Institute Intramural Research Program.


Assuntos
Grupos de Populações Continentais/estatística & dados numéricos , Grupos Étnicos/estatística & dados numéricos , Mortalidade Prematura/tendências , Adulto , Distribuição por Idade , Idoso , Atestado de Óbito , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade Prematura/etnologia , Distribuição por Sexo , Estados Unidos/epidemiologia
19.
Cancer Epidemiol Biomarkers Prev ; 26(5): 769-778, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28035020

RESUMO

Background: Cigarettes are well known to cause cancer, but less is known about the risks of other tobacco products and use of more than one product.Methods: We examined cancer incidence in relation to exclusive use of six tobacco products [cigarettes, other combustibles (pipe, cigar, cigarillo), and smokeless tobacco (chewing tobacco, snuff)] in the Agricultural Health Study. We also examined the added cancer risks associated with use of cigarettes and other tobacco products.Results: In our study population of 84,015, ever use of smokeless tobacco was higher than the general United States population, whereas cigarette use was lower and other combustible product use was about the same. The strongest associations for exclusive ever use were for lung cancer [cigarettes HR = 15.48; 95% confidence interval (CI), 11.95-20.06; other combustible tobacco HR = 3.44; 95% CI, 1.53-7.71; smokeless tobacco HR = 2.21; 95% CI, 1.11-4.42]. Compared with exclusive cigarette smokers, cigarette smokers who additionally ever-used another combustible product had higher risks of smoking-related cancers (HR = 1.16; 95% CI, 1.04-1.30), especially among those who smoked cigarettes for more than 15 years.Conclusions and Impact: Cigarette smokers who additionally ever used smokeless tobacco had cancer risks similar to exclusive cigarette smokers. Users of cigarettes and other combustible tobacco may have higher risks of certain cancers than exclusive cigarette users. Cancer Epidemiol Biomarkers Prev; 26(5); 769-78. ©2016 AACR.


Assuntos
Neoplasias/epidemiologia , Neoplasias/etiologia , Produtos do Tabaco/efeitos adversos , Uso de Tabaco/efeitos adversos , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Uso de Tabaco/epidemiologia , Estados Unidos
20.
JAMA Intern Med ; 177(1): 87-95, 2017 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-27918784

RESUMO

Importance: A growing proportion of US smokers now smoke fewer than 10 cigarettes per day (CPD), and that proportion will likely rise in the future. The health effects of smoking only a few CPD over one's lifetime are less understood than are the effects of heavier smoking, although many smokers believe that their level is modest. Objective: To evaluate the associations of long-term smoking of fewer than 1 or 1 to 10 CPD (low intensity) with all-cause and cause-specific mortality compared with never smoking cigarettes. Design, Setting, and Participants: Prospective cohort study of 290 215 adults in the National Institutes of Health-AARP (formerly known as the American Association of Retired Persons) Diet and Health Study who were aged 59 to 82 years in calendar years 2004-2005 (baseline). Data were gathered with a questionnaire assessing lifetime cigarette smoking history. Hazard ratios (HRs) and 95% CIs were determined for all-cause mortality and cause-specific mortality through the end of 2011. Hazard ratios and 95% CIs were estimated using Cox proportional hazards regression models using age as the underlying time metric and adjusted for sex, race/ethnicity, educational level, physical activity, and alcohol intake. Data analysis was conducted from December 15, 2015, to September 30, 2016. Exposures: Current and historical smoking intensity during 9 previous age periods (from <15 years to ≥70 years) over the lifetime assessed on the 2004-2005 questionnaire. Main Outcomes and Measures: All-cause and cause-specific mortality among current, former, and never smokers. Results: Of the 290 215 cohort participants who completed the 2004-2005 questionnaire, 168 140 were men (57.9%); the mean (SD) age was 71 (5.3) years (range, 59-82 years). Most people who smoked fewer than 1 or 1 to 10 CPD at baseline reported smoking substantially higher numbers of CPD earlier in their lives. Nevertheless, 159 (9.1%) and 1493 (22.5%) of these individuals reported consistently smoking fewer than 1 or 1 to 10 CPD in each age period that they smoked, respectively. Relative to never smokers, consistent smokers of fewer than 1 CPD (HR, 1.64; 95% CI, 1.07-2.51) and 1 to 10 CPD (HR, 1.87; 95% CI, 1.64-2.13) had a higher all-cause mortality risk. Associations were similar in women and men for all-cause mortality and were observed across a range of smoking-related causes of death, with an especially strong association with lung cancer (HR, 9.12; 95% CI, 2.92-28.47, and HR, 11.61; 95% CI, 8.25-16.35 for <1 and 1-10 CPD, respectively). Former smokers who had consistently smoked fewer than 1 or 1 to 10 CPD had progressively lower risks with younger age at cessation. For example, the HRs for consistent smokers of fewer than 1 and 1 to 10 CPD who quit at 50 years or older were 1.44 (95% CI, 1.12-1.85) and 1.42 (95% CI, 1.27-1.59), respectively. Conclusions and Relevance: This study provides evidence that individuals who smoke fewer than 1 or 1 to 10 CPD over their lifetime have higher mortality risks than never smokers and would benefit from cessation. These results provide further evidence that there is no risk-free level of exposure to tobacco smoke.


Assuntos
Fumar/mortalidade , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Estados Unidos/epidemiologia
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