Prediagnostic circulating inflammation markers and endometrial cancer risk in the prostate, lung, colorectal and ovarian cancer (PLCO) screening trial.
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ABSTRACT:
SUBMITTER: Trabert B
PROVIDER: S-EPMC5159268 | biostudies-literature | 2017 Feb
REPOSITORIES: biostudies-literature
Publications
Prediagnostic circulating inflammation markers and endometrial cancer risk in the prostate, lung, colorectal and ovarian cancer (PLCO) screening trial.
Trabert Britton B Eldridge Ronald C RC Pfeiffer Ruth M RM Shiels Meredith S MS Kemp Troy J TJ Guillemette Chantal C Hartge Patricia P Sherman Mark E ME Brinton Louise A LA Black Amanda A Chaturvedi Anil K AK Hildesheim Allan A Berndt Sonja I SI Safaeian Mahboobeh M Pinto Ligia L Wentzensen Nicolas N
International journal of cancer 20161107 3
Inflammation is proposed to increase risk of developing endometrial cancer, but few prospective epidemiologic studies have investigated the relationship between circulating inflammation markers and endometrial cancer risk. In a nested case-control study within the PLCO Screening Trial we measured serum levels of 64 inflammation-related biomarkers in 284 incident endometrial cancer cases and 284 matched controls. Using multivariable logistic regression inflammation markers were evaluated individu ...[more]
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Project description:OBJECTIVE:Pro-inflammatory mechanisms may explain the increased ovarian cancer risk linked to more lifetime ovulations, endometriosis, and exposure to talc and asbestos, as well as decreased risk with non-steroidal anti-inflammatory drugs. Limited data are available to estimate ovarian cancer risk associated with levels of circulating inflammatory markers. METHODS:We conducted a nested case-control study within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Pre-diagnostic serum levels of 46 inflammation-related biomarkers (11 with a priori hypotheses; 35 agnostic) were measured in 149 incident ovarian cancer cases and 149 matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression and adjusted for identified covariates. RESULTS:Increased ovarian cancer risk was associated with elevated levels of C-reactive protein (CRP) [tertile (T)3 vs. T1: OR (95% CI) 2.04 (1.06-3.93), p-trend=0.03], interleukin (IL)-1? [detectable vs. undetectable: 2.23 (1.14-4.34)] and tumor necrosis factor alpha (TNF-?) [T3 vs. T1: 2.21 (1.06-4.63), p-trend=0.04]. Elevated IL-8 was non-significantly associated with risk [T3 vs. T1: 1.86 (0.96-3.61), p-trend=0.05]. In analyses restricted to serous ovarian cancer (n=83), the associations with CRP and IL-8 remained or strengthened [CRP T3 vs. T1: 3.96 (1.14-11.14), p-trend=0.008; IL-8 T3 vs. T1: 3.05 (1.09-8.51), p-trend=0.03]. Elevated levels of CRP and TNF-? remained positively associated with ovarian cancer risk in analysis restricted to specimens collected at least 5years before diagnosis (n=56). CONCLUSION:These results suggest that CRP, IL-1?, IL-8, and TNF-? are associated with increased risk of subsequently developing ovarian cancer.
| S-EPMC4254357 | biostudies-literature
Project description:BackgroundWhite blood cell (WBC) DNA may contain methylation patterns that are associated with subsequent breast cancer risk. Using a high-throughput array and samples collected, on average, 1.3 years prior to diagnosis, a case-cohort analysis nested in the prospective Sister Study identified 250 individual CpG sites that were differentially methylated between breast cancer cases and noncases. We examined five of the top 40 CpG sites in a case-control study nested in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) Cohort.MethodsWe investigated the associations between prediagnostic WBC DNA methylation in 297 breast cancer cases and 297 frequency-matched controls. Two WBC DNA specimens from each participant were used: a proximate sample collected 1 to 2.9 years and a distant sample collected 4.2-7.3 years prior to diagnosis in cases or the comparable timepoints in controls. WBC DNA methylation level was measured using targeted bisulfite amplification sequencing. We used logistic regression to obtain ORs and 95% confidence intervals (CI).ResultsA one-unit increase in percent methylation in ERCC1 in proximate WBC DNA was associated with increased breast cancer risk (adjusted OR = 1.29; 95% CI, 1.06-1.57). However, a one-unit increase in percent methylation in ERCC1 in distant WBC DNA was inversely associated with breast cancer risk (adjusted OR = 0.83; 95% CI, 0.69-0.98). None of the other ORs met the threshold for statistical significance.ConclusionsThere was no convincing pattern between percent methylation in the five CpG sites and breast cancer risk.ImpactThe link between prediagnostic WBC DNA methylation marks and breast cancer, if any, is poorly understood.
| S-EPMC10825794 | biostudies-literature
Project description:BackgroundThe prostate component of the Prostate, Lung, Colorectal, and Ovarian (PLCO) randomized screening trial demonstrated no mortality effect of screening. Here we analyze prostate cancer specific survival in PLCO and its relation to screening.Methods76,693 men aged 55-74 were randomized to usual care (n = 38,350) or intervention (n = 38,343). Intervention arm men received annual prostate-specific antigen (6 years) and digital rectal exam (4 years). Men were followed for cancer diagnosis and mortality through 13 years. Medical record abstractors confirmed prostate cancer diagnoses, stage and grade. Prostate-specific survival in PLCO cases was analyzed using Kaplan-Meier analysis and proportional hazards modeling. We utilized data from the Surveillance, Epidemiology and End Results (SEER) program to compute expected survival in PLCO and compared this to observed.ResultsThere was no significant difference in prostate-specific survival rates between arms; 10 year survival rates were 94.7% (intervention, n = 4250 cases) versus 93.5% (usual care, n = 3815 cases). Within the intervention arm, cases never screened in PLCO had lower 10 year survival rates (82%) than screen detected or interval (following a negative screen) cases, both around 95.5%. The ratio of observed to expected 10 year prostate-specific death (1-survival) rates was 0.59 (95% CI: 0.51-0.68) for all PLCO cases, 0.66 (95% CI: 0.51-0.81) for Gleason 5-7 cases and 1.07 (95% CI: 0.87-1.3) for Gleason 8-10 cases.ConclusionProstate cancer specific survival in PLCO was comparable across arms and significantly better than expected based on nationwide population data. How much of the better survival is due to a healthy volunteer effect and to lead-time and overdiagnosis biases is not readily determinable.
| S-EPMC3582194 | biostudies-literature
Project description:Regular aspirin use may decrease cancer risk by reducing chronic inflammation. However, associations between aspirin use and circulating markers of inflammation have not been well studied.Serum levels of 78 inflammatory markers were measured in 1,819 55- to 74-year-old men and women in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Data were combined from three completed case-control studies and reweighted to the PLCO screening arm. Self-reported aspirin and ibuprofen use (number of tablets taken per day/week/month) over the previous 12 months was collected at baseline. Associations between (i) nonregular (<4 tablets/month), (ii) low (1-4 tablets/week), (iii) moderate (1 tablet/day), or (iv) high (2+ tablets/day) regular aspirin or ibuprofen use and marker levels were assessed with weighted logistic regression.Aspirin use was nominally associated with (Ptrend across categories ? 0.05) decreased levels of chemokine C-C motif ligand 15 [CCL15; OR, 0.5; 95% confidence intervals (CI), 0.3-0.8; moderate versus nonregular use]; soluble vascular endothelial growth factor receptor 2 (sVEGFR2; OR, 0.7; 95% CI, 0.4-1.0); soluble tumor necrosis factor receptor 1 (sTNFR1; OR, 0.6; 95% CI, 0.4-0.9) and increased levels of CCL13 (OR, 1.3; 95% CI, 0.8-2.1); CCL17 (OR, 1.1; 95% CI, 0.7-1.9) and interleukin 4 (IL4; OR, 1.6; 95% CI, 0.9-2.8). Trends were not statistically significant following correction for multiple comparisons. Likewise, no statistically significant associations were observed between ibuprofen use and marker levels.No significant associations were observed between regular aspirin use and the inflammatory markers assessed.Additional studies are needed to better understand the relationship between aspirin use, chronic inflammation, and cancer risk.
| S-EPMC4417370 | biostudies-other
Project description:BACKGROUND:Circulating adipokine levels may be associated with endometrial cancer risk, yet few studies have evaluated these markers prospectively. METHODS:We conducted a nested case-control study of postmenopausal women in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (n = 78,216), including 167 incident endometrial cancer cases and 327 controls that were matched on age, study center, race, study year of diagnosis, year of blood draw, time of day of blood draw, and menopausal hormone therapy (MHT) use. Adipokine and estradiol levels were categorized into tertiles (T). ORs and 95% confidence intervals (CIs) for the associations of adiponectin, leptin, and visfatin with endometrial cancer risk were estimated by conditional logistic regression, adjusting for known endometrial cancer risk factors, including body mass index (BMI) and circulating estradiol levels. RESULTS:Adiponectin levels were inversely associated with risk of endometrial cancer [ORT3vsT1 = 0.48; 95% CI, 0.29-0.80); Ptrend < 0.01], whereas elevated leptin levels showed a positive association [2.77 (1.60-4.79); Ptrend < 0.01]. These results remained significant after adjustment for estradiol, but not after further adjustment for BMI. When analyses were restricted to non-MHT users, associations of adiponectin and leptin were stronger and remained significant after adjustment for estradiol and BMI [0.25 (0.08-0.75); Ptrend = 0.01 and 4.72 (1.15-19.38); Ptrend = 0.02, respectively]. Nonsignificant positive associations were observed for visfatin. CONCLUSION:Adipokines may influence endometrial cancer risk through pathways other than estrogen-mediated cell growth in postmenopausal women not currently on MHT. IMPACT:Understanding how adipokines influence endometrial cancer risk may help to elucidate biological mechanisms important for the observed obesity-endometrial cancer association.
| S-EPMC3819202 | biostudies-literature
Project description:BackgroundThe 5-year overall survival rate of lung cancer patients is approximately 15%. Most patients are diagnosed with advanced-stage disease and have shorter survival rates than patients with early-stage disease. Although screening for lung cancer has the potential to increase early diagnosis, it has not been shown to reduce lung cancer mortality rates. In 1993, the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial was initiated specifically to determine whether screening would reduce mortality rates from PLCO cancers.MethodsA total of 77 464 participants, aged 55-74 years, were randomly assigned to the intervention arm of the PLCO Cancer Screening Trial between November 8, 1993, and July 2, 2001. Participants received a baseline chest radiograph (CXR), followed by three annual single-view CXRs at the 10 US screening centers. Cancers were classified as screen detected and nonscreen detected (interval or never screened) and according to tumor histology. The positivity rates of screen-detected cancers and positive predictive values (PPVs) were calculated. Because 51.6% of the participants were current or former smokers, logistic regression analysis was performed to control for smoking status. All statistical tests were two-sided.ResultsCompliance with screening decreased from 86.6% at baseline to 78.9% at the last screening. Overall positivity rates were 8.9% at baseline and 6.6%-7.1% at subsequent screenings; positivity rates increased modestly with smoking risk categories (P(trend) < .001). The PPVs for all participants were 2.0% at baseline and 1.1%, 1.5%, and 2.4% at years 1, 2, and 3, respectively; PPVs in current smokers were 5.9% at baseline and 3.3%, 4.2%, and 5.6% at years 1, 2, and 3, respectively. A total of 564 lung cancers were diagnosed, of which 306 (54%) were screen-detected cancers and 87% were non-small cell lung cancers. Among non-small cell lung cancers, 59.6% of screen-detected cancers and 33.3% of interval cancers were early (I-II) stage.ConclusionsThe PLCO Cancer Screening Trial demonstrated the ability to recruit, retain, and screen a large population over multiple years at multiple centers. A higher proportion of screen-detected lung cancers were early stage, but a conclusion on the effectiveness of CXR screening must await final PLCO results, which are anticipated at the end of 2015.
| S-EPMC2873186 | biostudies-literature
Project description:Mutagen challenge and DNA repair assays have been used in case-control studies for nearly three decades to assess human cancer risk. The findings still engender controversy because blood was drawn after cancer diagnosis so the results may be biased, a type called 'reverse causation'. We therefore used Epstein-Barr virus-transformed lymphoblastoid cell lines established from prospectively collected peripheral blood samples to evaluate lung cancer risk in relation to three DNA repair assays: alkaline Comet assay, host cell reactivation (HCR) assay with the mutagen benzo[a]pyrene diol epoxide and the bleomycin mutagen sensitivity assay. Cases (n = 117) were diagnosed with lung cancer between 0.3 and 6 years after blood collection and controls (n = 117) were frequency matched on calendar year and age at blood collection, gender and smoking history; all races were included. Case and control status was unknown to laboratory investigators. In unconditional logistic regression analyses, statistically significantly increased lung cancer odds ratios (OR(adjusted)) were observed for bleomycin mutagen sensitivity as quartiles of chromatid breaks/cell [relative to the lowest quartile, OR = 1.2, 95% confidence interval (CI): 0.5-2.5; OR = 1.4, 95% CI: 0.7-3.1; OR = 2.1, 95% CI: 1.0-4.4, respectively, P(trend) = 0.04]. The magnitude of the association between the bleomycin assay and lung cancer risk was modest compared with those reported in previous lung cancer studies but was strengthened when we included only incident cases diagnosed more than a year after blood collection (P(trend) = 0.02), supporting the notion the assay may be a measure of cancer susceptibility. The Comet and HCR assays were unrelated to lung cancer risk.
| S-EPMC3010173 | biostudies-literature
Project description:BACKGROUND:Factors contributing to chronic inflammation appear to be associated with increased risk of ovarian cancer. The purpose of this study was to assess the association between circulating levels of inflammation mediators and subsequent risk of ovarian cancer. METHODS:We conducted a case-control study of 230 cases and 432 individually matched controls nested within three prospective cohorts to evaluate the association of prediagnostic circulating levels of inflammation-related biomarkers (IL-1?, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p40, IL-12p70, IL-13, TNF?, IL-1Ra, sIL-1RII, sIL-2Ra, sIL-4R, sIL-6R, sTNF-R1, and sTNF-R2) measured using Luminex xMap technology with risk of ovarian cancer. RESULTS:We observed a trend across quartiles for IL-2 (OR(Q4 vs. Q1): 1.57, 95% CI: 0.98-2.52, P = 0.07), IL-4 (OR(Q4 vs. Q1): 1.50, 95% CI: 0.95-2.38, P = 0.06), IL-6 (OR(Q4 vs. Q1): 1.63, 95% CI: 1.03-2.58, P = 0.03), IL-12p40 (OR(Q4 vs. Q1): 1.60, 95% CI: 1.02-2.51, P = 0.06), and IL-13 (OR(Q4 vs. Q1): 1.42, 95% CI: 0.90-2.26, P = 0.11). Trends were also observed when cytokines were modeled on the continuous scale for IL-4 (P trend = 0.01), IL-6 (P trend = 0.01), IL-12p40 (P trend = 0.01), and IL-13 (P trend = 0.04). ORs were not materially different after excluding cases diagnosed less than 5 years after blood donation or when limited to serous tumors. CONCLUSIONS AND IMPACT:This study provides the first direct evidence that multiple inflammation markers, specifically IL-2, IL-4, IL-6, IL-12, and IL-13, may be associated with risk of epithelial ovarian cancer, and adds to the evidence that inflammation is involved in the development of this disease.
| S-EPMC3089656 | biostudies-literature
Project description:BackgroundOvarian cancer is the fifth most common cause of cancer death among women in the US, yet few modifiable risk factors have been established. Diets high in glycemic index (GI) and glycemic load (GL) have been linked to several cancers, but epidemiologic studies of ovarian cancer have yielded inconsistent results.ObjectiveIn this study, we aimed to examine associations between GI or GL and ovarian cancer.MethodsWe used prospective data from the Prostate, Lung, Colorectal, and Ovarian cohort. GI and GL were calculated from validated FFQs. Participants were women who were aged 60 to 74 y, did not have a history of cancer, and had both ovaries. Cox proportional hazard models were used to calculate HRs and 95% CIs for risk of ovarian cancer associated with quartiles of GI and GL. Analyses were performed separately for those who completed the dietary questionnaire at baseline (DQX) or later in the study (DHQ).ResultsFrom the DQX sample set, 181 cases were identified among 24,633 women with median follow-up of 12.1 y; there were 211 cases among 42,410 women in the DHQ set, with median follow-up of 8.9 y. After adjusting for age at dietary questionnaire completion, year of randomization, year of questionnaire, study center, and oral contraceptive use, the risk of ovarian cancer decreased by 43% (HR: 0.57; 95% CI: 0.37, 0.88) among those in the highest compared with those in the lowest quartile of GL (DQX). Those in the highest compared with those in the lowest quartile of GI (DHQ), had a 38% lower risk (HR: 0.62; 95% CI: 0.42, 1.00).ConclusionsWe observed lower risk of ovarian cancer associated with higher GI and GL. Results should be interpreted with caution as they may have been influenced by limitations including lack of variability in dietary intake. Additional studies are needed to better understand what is driving these associations.
| S-EPMC8169811 | biostudies-literature
Project description:We tested the hypothesis that genes involved in the alcohol oxidation pathway modify the association between alcohol intake and breast cancer. Subjects were women aged 55-74 at baseline from the screening arm of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Incident breast cancers were identified through annual health surveys. Controls were frequency matched to cases by age and year of entry into the trial. A self-administered food frequency questionnaire queried frequency and usual serving size of beer, wine or wine coolers, and liquor. Three SNPs in genes in the alcohol metabolism pathway were genotyped: alcohol dehydrogenase 2, alcohol dehydrogenase 3, and CYP2E1. The study included 1,041 incident breast cancer cases and 1,070 controls. In comparison to non-drinkers, the intake of any alcohol significantly increased the risk of breast cancer, and this risk increased with each category of daily alcohol intake (OR 2.01, 95% CI 1.14, 3.53) for women who drank three or more standard drinks per day. Stratification by genotype revealed significant gene/environment interactions. For the ADH1B gene, there were statistically significant associations between all levels of alcohol intake and risk of breast cancer (all OR > 1.34 and all lower CI > 1.01), while for women with the GA or AA genotype, there were no significant associations between alcohol intake and risk of breast cancer. Alcohol intake, genes involved in alcohol metabolism and their interaction increase the risk of breast cancer in post-menopausal women. This information could be useful for primary care providers to personalize information about breast cancer risk reduction.
| S-EPMC3584637 | biostudies-literature