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1.
Am J Epidemiol ; 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31602476

RESUMO

Higher body mass index (BMI) is associated with increased risk of pancreatic cancer in epidemiologic studies but BMI has usually been assessed at older ages, potentially underestimating the full impact of excess weight. We examined the association between BMI and pancreatic cancer mortality among 963,317 adults aged 30-89 years at enrollment into Cancer Prevention Study-II in 1982. During follow-up through 2014, 8,354 participants died of pancreatic cancer. Hazard ratios (HRs) per 5 BMI-units, calculated using proportional hazards regression, declined steadily with age at BMI assessment, from 1.25 (95% confidence interval (CI) 1.18, 1.33) in those aged 30-49 at enrollment to 1.13 (95% CI 1.02, 1.26) in those aged 70-89 (p-trend=0.005). Based on a HR of 1.25 per 5 BMI-units at age 45, we estimate 28% of US pancreatic cancer deaths in those born from 1970-74 will be attributable to BMI≥25, nearly twice the equivalent proportion in those born in the 1930s, a birth cohort with much lower BMI in middle age. These results suggest BMI before age 50 is more strongly associated with pancreatic cancer risk than BMI at older ages and underscore the importance of avoiding excess weight gain before middle age for preventing this highly fatal cancer.

2.
Eur Urol Oncol ; 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31378665

RESUMO

BACKGROUND: Little is known about the underlying molecular mechanisms of prostate cancer, especially advanced and fatal prostate cancer. OBJECTIVE: To examine associations of prediagnostic plasma metabolomic profiles with advanced and fatal prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: In a case-cohort study of the Cancer Prevention Study-II Nutrition Cohort, of 14 210 cancer-free men with a blood sample in 1998-2001, 129 were diagnosed with advanced prostate cancer (T3-T4 or N1 or M1) through June 2013 and 112 died from prostate cancer through December 2014. Plasma samples from advanced and fatal cases, and a randomly selected subcohort of 347 men were metabolically profiled using untargeted mass spectroscopy-based platforms. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Prentice-weighted Cox proportional hazards regression models were used to assess associations of 699 known metabolites with advanced and fatal prostate cancer. RESULTS AND LIMITATIONS: Two metabolites derived from fatty acid metabolism (ethylmalonate and butyrylcarnitine), aspartate, sphingomyelin (d18:1/18:0), and two γ-glutamyl amino acids (γ-glutamylmethionine and γ-glutamylglutamine) were statistically significantly associated (false discovery rate <0.2) with fatal prostate cancer. One standard deviation (SD) increase in each γ-glutamyl amino acid was associated with 34-38% decreased risk, whereas one SD increase in each of the other metabolites was associated with 45-53% increased risk. A metabolic risk score based on four of these metabolites (excluding butyrylcarnitine and γ-glutamylglutamine, which were not independent predictors) was strongly associated with fatal prostate cancer (relative risk per SD: 2.72, 95% confidence interval: 2.05-3.60). No metabolites were statistically significantly associated with advanced prostate cancer. These results were observational and may not be causal. CONCLUSIONS: These findings identified metabolic pathways that are altered in the development of fatal prostate cancer. Further research into these pathways may provide insights into the etiology of fatal prostate cancer. PATIENT SUMMARY: In a large follow-up study of cancer-free men, those with a certain metabolomic profile had a higher risk of dying from prostate cancer.

3.
Int J Cancer ; 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31276202

RESUMO

Cell-mediated immune suppression may play an important role in lung carcinogenesis. We investigated the associations for circulating levels of tryptophan, kynurenine, kynurenine:tryptophan ratio (KTR), quinolinic acid (QA) and neopterin as markers of immune regulation and inflammation with lung cancer risk in 5,364 smoking-matched case-control pairs from 20 prospective cohorts included in the international Lung Cancer Cohort Consortium. All biomarkers were quantified by mass spectrometry-based methods in serum/plasma samples collected on average 6 years before lung cancer diagnosis. Odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with individual biomarkers were calculated using conditional logistic regression with adjustment for circulating cotinine. Compared to the lowest quintile, the highest quintiles of kynurenine, KTR, QA and neopterin were associated with a 20-30% higher risk, and tryptophan with a 15% lower risk of lung cancer (all ptrend < 0.05). The strongest associations were seen for current smokers, where the adjusted ORs (95% CIs) of lung cancer for the highest quintile of KTR, QA and neopterin were 1.42 (1.15-1.75), 1.42 (1.14-1.76) and 1.45 (1.13-1.86), respectively. A stronger association was also seen for KTR and QA with risk of lung squamous cell carcinoma followed by adenocarcinoma, and for lung cancer diagnosed within the first 2 years after blood draw. This study demonstrated that components of the tryptophan-kynurenine pathway with immunomodulatory effects are associated with risk of lung cancer overall, especially for current smokers. Further research is needed to evaluate the role of these biomarkers in lung carcinogenesis and progression.

4.
Am J Clin Nutr ; 109(5): 1439-1451, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31051511

RESUMO

BACKGROUND: Healthy diet patterns are associated with lower risk of cancer and other chronic diseases. Metabolomics has the potential to expand dietary biomarker development to include dietary patterns, which may provide a complement or alternative to self-reported diet. OBJECTIVE: This study examined the correlation of serum untargeted metabolomic markers with 4 diet pattern scores-the alternate Mediterranean diet score (aMED), alternate Healthy Eating Index (AHEI)-2010, the Dietary Approaches to Stop Hypertension (DASH) diet, and the Healthy Eating Index (HEI)-2015-and used multivariate methods to identify discriminatory metabolites for each pattern. METHODS: Among 1367 US postmenopausal women with serum metabolomic data in the Cancer Prevention Study-II Nutrition Cohort, we conducted partial correlation analysis, adjusted for demographic and lifestyle variables, to examine cross-sectional correlations between serum metabolomic markers and healthy diet pattern scores. In a randomly selected "training" set (50%), we conducted orthogonal partial least-squares discriminant analysis to identify metabolites that discriminated the top from bottom diet score quintiles. Combinations of metabolites with a variable importance in projection (VIP) score ≥2.5 were tested for predictability in the "testing" set based on the use of receiver operating characteristic curves. RESULTS: Out of 1186 metabolites, 32 unique metabolites were considered discriminatory based on a VIP score ≥2.5 in the training dataset with some overlap across scores (aMED = 16; AHEI = 17; DASH = 13; HEI = 12). Spearman partial correlation analyses, applying a cut-point (|r| ≥ 0.15) and Bonferroni correction (P < 1.05 × 10-5), identified similar key metabolites. The top 5 metabolites for each pattern mostly distinguished high compared with low scores; 4 of the 5 (fish-derived) metabolites were the same for aMED and AHEI, 2 of which were identified for HEI; 4 DASH metabolites were unique. CONCLUSIONS: Metabolomic methods that used a split-sample approach identified potential biomarkers for 4 healthy diet patterns. Similar metabolites across scores reflect fish consumption in healthy dietary patterns. These findings should be replicated in independent populations.

6.
BMJ ; 364: k4981, 2019 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-30606716

RESUMO

OBJECTIVES: To conduct a comprehensive analysis of prospectively measured circulating high sensitivity C reactive protein (hsCRP) concentration and risk of lung cancer overall, by smoking status (never, former, and current smokers), and histological sub-type. DESIGN: Nested case-control study. SETTING: 20 population based cohort studies in Asia, Europe, Australia, and the United States. PARTICIPANTS: 5299 patients with incident lung cancer, with individually incidence density matched controls. EXPOSURE: Circulating hsCRP concentrations in prediagnostic serum or plasma samples. MAIN OUTCOME MEASURE: Incident lung cancer diagnosis. RESULTS: A positive association between circulating hsCRP concentration and the risk of lung cancer for current (odds ratio associated with a doubling in hsCRP concentration 1.09, 95% confidence interval 1.05 to 1.13) and former smokers (1.09, 1.04 to 1.14) was observed, but not for never smokers (P<0.01 for interaction). This association was strong and consistent across all histological subtypes, except for adenocarcinoma, which was not strongly associated with hsCRP concentration regardless of smoking status (odds ratio for adenocarcinoma overall 0.97, 95% confidence interval 0.94 to 1.01). The association between circulating hsCRP concentration and the risk of lung cancer was strongest in the first two years of follow-up for former and current smokers. Including hsCRP concentration in a risk model, in addition to smoking based variables, did not improve risk discrimination overall, but slightly improved discrimination for cancers diagnosed in the first two years of follow-up. CONCLUSIONS: Former and current smokers with higher circulating hsCRP concentrations had a higher risk of lung cancer overall. Circulating hsCRP concentration was not associated with the risk of lung adenocarcinoma. Circulating hsCRP concentration could be a prediagnostic marker of lung cancer rather than a causal risk factor.


Assuntos
Proteína C-Reativa/metabolismo , Carcinoma de Células Grandes/sangue , Carcinoma de Células Pequenas/sangue , Carcinoma de Células Escamosas/sangue , Neoplasias Pulmonares/sangue , Fumar/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Biomarcadores Tumorais/sangue , Carcinoma de Células Grandes/epidemiologia , Carcinoma de Células Pequenas/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Estudos de Casos e Controles , Ex-Fumantes/estatística & dados numéricos , Feminino , Humanos , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade , não Fumantes/estatística & dados numéricos , Razão de Chances , Estudos Prospectivos , Medição de Risco , Sensibilidade e Especificidade , Fumantes/estatística & dados numéricos , Fumar/epidemiologia , Adulto Jovem
9.
Int J Cancer ; 2018 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-30499135

RESUMO

Vitamin B supplementation can have side effects for human health, including cancer risk. We aimed to elucidate the role of vitamin B12 in lung cancer aetiology via direct measurements of pre-diagnostic circulating vitamin B12 concentrations in a nested case-control study, complemented with a Mendelian randomization (MR) approach in an independent case-control sample. We used pre-diagnostic biomarker data from 5,183 case-control pairs nested within 20 prospective cohorts, and genetic data from 29,266 cases and 56,450 controls. Exposures included directly measured circulating vitamin B12 in pre-diagnostic blood samples from the nested case-control study, and 8 single nucleotide polymorphisms associated with vitamin B12 concentrations in the MR study. Our main outcome of interest was increased risk for lung cancer, overall and by histological subtype, per increase in circulating vitamin B12 concentrations. We found circulating vitamin B12 to be positively associated with overall lung cancer risk in a dose response fashion (odds ratio for a doubling in B12 [ORlog2B12 ] = 1.15, 95% confidence interval (95%CI) = 1.06-1.25). The MR analysis based on 8 genetic variants also indicated that genetically determined higher vitamin B12 concentrations were positively associated with overall lung cancer risk (OR per 150 pmol/L standard deviation increase in B12 [ORSD ]= 1.08, 95%CI= 1.00-1.16). Considering the consistency of these two independent and complementary analyses, these findings support the hypothesis that high vitamin B12 status increases the risk of lung cancer. This article is protected by copyright. All rights reserved.

10.
Nat Commun ; 9(1): 4616, 2018 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-30397198

RESUMO

Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10-15), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62-4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification.

11.
Am J Epidemiol ; 2018 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-30325407

RESUMO

Social isolation is associated with higher mortality in studies of mostly white adults, yet associations among black adults is unclear. This prospective cohort study evaluated whether associations of social isolation with all-cause, cardiovascular disease and cancer mortality differ by race and sex. Adults enrolled into Cancer Prevention Study-II in 1982/1983 were followed for mortality through 2012 (n = 580,182). Sex- and race-specific multivariable-adjusted hazard ratios and 95% confidence intervals were estimated for associations of a five-point social isolation score with risk of death. Social isolation was associated with all-cause mortality in all subgroups (P-trend ≤ 0.005); for the most versus the least isolated, the hazard ratios (95% confidence intervals) were 2.34 (1.58, 3.46) and 1.60 (1.41, 1.82) among black and white men, respectively (P-interaction = 0.40), and 2.13 (1.44, 3.15) and 1.84 (1.68, 2.01) among black and white women, respectively (P-interaction = 0.89). The association did not differ between black men and women (P-interaction = 0.33) but was slightly stronger in white women than white men (P-interaction = 0.01). Social isolation was associated with cardiovascular disease mortality in each subgroup (P-trend < 0.03) but with cancer mortality only among whites (P-trend < 0.0001). Subgroup differences in the influence of specific social isolation components were identified. Identifying and intervening with socially isolated adults could improve health outcomes.

12.
Artigo em Inglês | MEDLINE | ID: mdl-30352818

RESUMO

BACKGROUND: Whether associations between circulating metabolites and prostate cancer are causal is unknown. We report on the largest study of metabolites and prostate cancer (2,291 cases and 2,661 controls) and appraise causality for a subset of the prostate cancer-metabolite associations using two-sample Mendelian randomization (MR). MATERIALS AND METHODS: The case-control portion of the study was conducted in nine UK centres with men aged 50-69 years who underwent prostate-specific antigen (PSA) screening for prostate cancer within the Prostate testing for cancer and Treatment (ProtecT) trial. Two data sources were used to appraise causality: a genome-wide association study (GWAS) of metabolites in 24,925 participants and a GWAS of prostate cancer in 44,825 cases and 27,904 controls within the Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. RESULTS: Thirty-five metabolites were strongly associated with prostate cancer (p <0.0014, multiple-testing threshold). These fell into four classes: i) lipids and lipoprotein subclass characteristics (total cholesterol and ratios, cholesterol esters and ratios, free cholesterol and ratios, phospholipids and ratios, and triglyceride ratios); ii) fatty acids and ratios; iii) amino acids; iv) and fluid balance. Fourteen top metabolites were proxied by genetic variables, but MR indicated these were not causal. CONCLUSIONS: We identified 35 circulating metabolites associated with prostate cancer presence, but found no evidence of causality for those 14 testable with MR. Thus, the 14 MR-tested metabolites are unlikely to be mechanistically important in prostate cancer risk. IMPACT: The metabolome provides a promising set of biomarkers that may aid prostate cancer classification.

13.
Metabolites ; 8(4)2018 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-30248901

RESUMO

Over-the-counter analgesic use is common and is typically assessed through self-report; therefore, it is subject to misclassification. Detection of drug metabolites in biofluids offers a viable tool for validating self-reported analgesic use. Thus, the aim of this study was to determine the utility of a metabolomics approach for the validation of acetaminophen and ibuprofen use in blood samples. Untargeted mass spectrometry-based metabolomics analysis was conducted in serum samples from 1547 women and plasma samples from 556 men. The presence of two metabolites each for acetaminophen and ibuprofen at levels at or above a defined cutoff value was used to determine concordance with self-reported use. For acetaminophen use based on the presence of both acetaminophen and acetamidophenylglucuronide, concordance was 98.5⁻100% among individuals reporting use today, and 79.8⁻91.4% for those reporting never or rare use. Ibuprofen use based on the presence of both carboxyibuprofen and hydroxyibuprofen resulted in concordance of 51.3⁻52.5% for individuals reporting use today and 99.4⁻100% for those reporting never or rare use. Our findings suggest that an untargeted metabolomics approach in blood samples may be useful for validating self-reported acetaminophen use. However, this approach appears unlikely to be suitable for validating ibuprofen use.

14.
Int J Epidemiol ; 47(6): 1760-1771, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29901778

RESUMO

Background: Self-reported smoking is the principal measure used to assess lung cancer risk in epidemiological studies. We evaluated if circulating cotinine-a nicotine metabolite and biomarker of recent tobacco exposure-provides additional information on lung cancer risk. Methods: The study was conducted in the Lung Cancer Cohort Consortium (LC3) involving 20 prospective cohort studies. Pre-diagnostic serum cotinine concentrations were measured in one laboratory on 5364 lung cancer cases and 5364 individually matched controls. We used conditional logistic regression to evaluate the association between circulating cotinine and lung cancer, and assessed if cotinine provided additional risk-discriminative information compared with self-reported smoking (smoking status, smoking intensity, smoking duration), using receiver-operating characteristic (ROC) curve analysis. Results: We observed a strong positive association between cotinine and lung cancer risk for current smokers [odds ratio (OR ) per 500 nmol/L increase in cotinine (OR500): 1.39, 95% confidence interval (CI): 1.32-1.47]. Cotinine concentrations consistent with active smoking (≥115 nmol/L) were common in former smokers (cases: 14.6%; controls: 9.2%) and rare in never smokers (cases: 2.7%; controls: 0.8%). Former and never smokers with cotinine concentrations indicative of active smoking (≥115 nmol/L) also showed increased lung cancer risk. For current smokers, the risk-discriminative performance of cotinine combined with self-reported smoking (AUCintegrated: 0.69, 95% CI: 0.68-0.71) yielded a small improvement over self-reported smoking alone (AUCsmoke: 0.66, 95% CI: 0.64-0.68) (P = 1.5x10-9). Conclusions: Circulating cotinine concentrations are consistently associated with lung cancer risk for current smokers and provide additional risk-discriminative information compared with self-report smoking alone.

15.
Nat Genet ; 50(7): 928-936, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29892016

RESUMO

Genome-wide association studies (GWAS) and fine-mapping efforts to date have identified more than 100 prostate cancer (PrCa)-susceptibility loci. We meta-analyzed genotype data from a custom high-density array of 46,939 PrCa cases and 27,910 controls of European ancestry with previously genotyped data of 32,255 PrCa cases and 33,202 controls of European ancestry. Our analysis identified 62 novel loci associated (P < 5.0 × 10-8) with PrCa and one locus significantly associated with early-onset PrCa (≤55 years). Our findings include missense variants rs1800057 (odds ratio (OR) = 1.16; P = 8.2 × 10-9; G>C, p.Pro1054Arg) in ATM and rs2066827 (OR = 1.06; P = 2.3 × 10-9; T>G, p.Val109Gly) in CDKN1B. The combination of all loci captured 28.4% of the PrCa familial relative risk, and a polygenic risk score conferred an elevated PrCa risk for men in the ninetieth to ninety-ninth percentiles (relative risk = 2.69; 95% confidence interval (CI): 2.55-2.82) and first percentile (relative risk = 5.71; 95% CI: 5.04-6.48) risk stratum compared with the population average. These findings improve risk prediction, enhance fine-mapping, and provide insight into the underlying biology of PrCa1.

16.
Nat Commun ; 9(1): 2256, 2018 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-29892050

RESUMO

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling.

18.
J Nutr ; 148(6): 932-943, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29767735

RESUMO

Background: Recent studies suggest that untargeted metabolomics is a promising tool to identify novel biomarkers of individual foods. However, few large cross-sectional studies with comprehensive data on habitual diet and circulating metabolites have been conducted. Objective: We aimed to identify potential food biomarkers and evaluate their predictive accuracy. Methods: We conducted a cross-sectional analysis of consumption of 91 food groups or items, assessed by a 152-item food-frequency questionnaire, in relation to 1186 serum metabolites measured by mass spectrometry-based platforms from 1369 nonsmoking postmenopausal women (mean age = 68.3 y). Diet-metabolite associations were selected by Pearson's partial correlation analysis (P < 4.63 × 10-7, |r| > 0.2). The predictive accuracy of the selected food metabolites was evaluated from the area under the curve (AUC) calculated from receiver operating characteristic analysis conducted among women in the top and bottom quintiles of dietary intake. Results: We identified 379 diet-metabolite associations. Forty-two food groups or items were correlated with 199 serum metabolites. We replicated 63 metabolites as biomarkers of habitual food intake reported in previous cross-sectional studies. Among those not previously shown to be associated with habitual diet, several are biologically plausible and were reported in acute feeding studies including: banana and dopamine 3-O-sulfate (r = 0.34, AUC = 76%) and dopamine 4-O-sulfate (r = 0.33, AUC = 74%), garlic and alliin (r = 0.24, AUC = 69%), N-acetylalliin (r = 0.27, AUC = 70%), and S-allylcysteine (r = 0.23, AUC = 69). Two unannotated metabolites were the strongest predictors for dark fish (X-02269, r = 0.51, AUC = 94%) and coffee intake (X-21442, r = 0.62, AUC = 98%). Conclusion: In this comprehensive, cross-sectional analysis of habitual food intake and serum metabolites among postmenopausal women, we identified several potentially novel food biomarkers and replicated others. Our findings contribute to the limited literature on food-based biomarkers and highlight the significant and promising role that large cohort studies with archived blood samples could play in this field. This study was registered at clinicaltrials.gov as NCT03282812.

19.
Cancer Epidemiol Biomarkers Prev ; 27(6): 665-672, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29700008

RESUMO

Background: Prior studies of prostate cancer survivors suggest that smoking might be associated with higher prostate cancer-specific mortality (PCSM) after diagnosis with prostate cancer. However, most of these studies were small, and questions remain regarding this association's strength and whether it persists after adjustment for stage and Gleason score.Methods: This analysis included men diagnosed with nonmetastatic prostate cancer between enrollment in the Cancer Prevention Study II Nutrition Cohort in 1992-1993 and June 2013. Cigarette smoking was self-reported at enrollment and updated in 1997 and every 2 years thereafter. Analyses of pre-diagnosis and post-diagnosis smoking included 9,781 and 9,111 prostate cancer cases, respectively, with vital status follow-up through 2014.Results: There were 672 deaths from prostate cancer in analyses of pre-diagnosis smoking and 554 in analyses of post-diagnosis smoking. In multivariable-adjusted Cox proportional hazards regression models including stage and Gleason score, both current smoking before diagnosis [HR = 1.50; 95% confidence interval (CI), 1.06-2.13] and current smoking after diagnosis (HR = 1.71; 95% CI, 1.09-2.67) were associated with higher PCSM compared to never smoking. Prostate cancer survivors who quit smoking <20 years before diagnosis were also at significantly higher risk of PCSM (HR = 1.29; 95% CI, 1.04-1.61).Conclusions: This large prospective study suggests that current smoking both before and after diagnosis of prostate cancer is associated with higher PCSM, even after accounting for stage and Gleason score.Impact: Our results provide evidence that smoking is a relevant prognostic factor for prostate cancer patients and that prostate cancer may be among the causes of death attributable to smoking. Cancer Epidemiol Biomarkers Prev; 27(6); 665-72. ©2018 AACR.

20.
J Natl Cancer Inst ; 110(1)2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-28922778

RESUMO

Background: Circulating concentrations of B vitamins and factors related to one-carbon metabolism have been found to be strongly inversely associated with lung cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The extent to which these associations are present in other study populations is unknown. Methods: Within 20 prospective cohorts from the National Cancer Institute Cohort Consortium, a nested case-control study was designed including 5364 incident lung cancer case patients and 5364 control subjects who were individually matched to case patients by age, sex, cohort, and smoking status. Centralized biochemical analyses were performed to measure circulating concentrations of vitamin B6, folate, and methionine, as well as cotinine as an indicator of recent tobacco exposure. The association between these biomarkers and lung cancer risk was evaluated using conditional logistic regression models. Results: Participants with higher circulating concentrations of vitamin B6 and folate had a modestly decreased risk of lung cancer risk overall, the odds ratios when comparing the top and bottom fourths (OR 4vs1 ) being 0.88 (95% confidence interval [CI] = 0.78 to 1.00) and 0.86 (95% CI = 0.74 to 0.99), respectively. We found stronger associations among men (vitamin B6: OR 4vs1 = 0.74, 95% CI = 0.62 to 0.89; folate: OR 4vs1 = 0.75, 95% CI = 0.61 to 0.93) and ever smokers (vitamin B6: OR 4vs1 = 0.78, 95% CI = 0.67 to 0.91; folate: OR 4vs1 = 0.87, 95% CI = 0.73 to 1.03). We further noted that the association of folate was restricted to Europe/Australia and Asia, whereas no clear association was observed for the United States. Circulating concentrations of methionine were not associated with lung cancer risk overall or in important subgroups. Conclusions: Although confounding by tobacco exposure or reverse causation cannot be ruled out, these study results are compatible with a small decrease in lung cancer risk in ever smokers who avoid low concentrations of circulating folate and vitamin B6.


Assuntos
Ácido Fólico/sangue , Neoplasias Pulmonares/epidemiologia , Metionina/sangue , Vitamina B 6/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Ásia/epidemiologia , Austrália/epidemiologia , Estudos de Casos e Controles , Cotinina/sangue , Europa (Continente)/epidemiologia , Feminino , Humanos , Incidência , Neoplasias Pulmonares/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Proteção , Fatores de Risco , Fatores Sexuais , Fumar/sangue , Fumar/epidemiologia , Estados Unidos/epidemiologia
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