23 research outputs found
Evaluating the Potential of Polygenic Risk Score to Improve Colorectal Cancer Screening
Background: Colorectal cancer has high incidence and associ-ated mortality worldwide. Screening programs are recommended for men and women over 50. Intermediate screens such as fecal immunochemical testing (FIT) select patients for colonoscopy with suboptimal sensitivity. Additional biomarkers could improve the current scenario. Methods: We included 2,893 individuals with a positive FIT test. They were classified as cases when a high-risk lesion for colorectal cancer was detected after colonoscopy, whereas the control group comprised individuals with low-risk or no lesions. 65 colorectal cancer risk genetic variants were geno-typed. Polygenic risk score (PRS) and additive models for risk prediction incorporating sex, age, FIT value, and PRS were generated. Results: Risk score was higher in cases compared with controls [per allele OR = 1.04; 95% confidence interval (CI), 1.02-1.06; P = 65), compared with those in the first decile (<= 54; OR = 2.22; 95% CI, 1.59-3.12; P < 0.0001). The model combining sex, age, FIT value, and PRS reached the highest accuracy for identifying patients with a high-risk lesion [cross-validated area under the ROC curve (AUROC): 0.64; 95% CI, 0.62-0.66]. Conclusions: This is the first investigation analyzing PRS in a two-step colorectal cancer screening program. PRS could improve current colorectal cancer screening, most likely for higher at-risk subgroups. However, its capacity is limited to predict colorectal cancer risk status and should be complemented by additional biomarkers.Impact: PRS has capacity for risk stratification of colorectal cancer suggesting its potential for optimizing screening strategies alongside with other biomarkers
Flavonoid and lignan intake and pancreatic cancer risk in the European prospective investigation into cancer and nutrition cohort.
Despite the potential cancer preventive effects of flavonoids and lignans, their ability to reduce pancreatic cancer risk has not been demonstrated in epidemiological studies. Our aim was to examine the association between dietary intakes of flavonoids and lignans and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 865 exocrine pancreatic cancer cases occurred after 11.3 years of follow-up of 477,309 cohort members. Dietary flavonoid and lignan intake was estimated through validated dietary questionnaires and the US Department of Agriculture (USDA) and Phenol Explorer databases. Hazard ratios (HR) and 95% confidence intervals (CIs) were calculated using age, sex and center-stratified Cox proportional hazards models, adjusted for energy intake, body mass index (BMI), smoking, alcohol and diabetes status. Our results showed that neither overall dietary intake of flavonoids nor of lignans were associated with pancreatic cancer risk (multivariable-adjusted HR for a doubling of intake = 1.03, 95% CI: 0.95-1.11 and 1.02; 95% CI: 0.89-1.17, respectively). Statistically significant associations were also not observed by flavonoid subclasses. An inverse association between intake of flavanones and pancreatic cancer risk was apparent, without reaching statistical significance, in microscopically confirmed cases (HR for a doubling of intake = 0.96, 95% CI: 0.91-1.00). In conclusion, we did not observe an association between intake of flavonoids, flavonoid subclasses or lignans and pancreatic cancer risk in the EPIC cohort.The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut Nation al de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), PI12/00002 co-funded by ERDF, PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); WCR (Grant Reference Number: 15-0391); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom).This is the final vesion of the article. It first appeared from Wiley via 10.1002/ijc.3019
Dietary and lifestyle determinants of acrylamide and glycidamide hemoglobin adducts in non-smoking postmenopausal women from the EPIC cohort
Purpose Acrylamide was classified as ‘probably carcinogenic’ to humans
in 1994 by the International Agency for Research on Cancer. In 2002,
public health concern increased when acrylamide was identified in
starchy, plant-based foods, processed at high temperatures. The purpose
of this study was to identify which food groups and lifestyle variables
were determinants of hemoglobin adduct concentrations of acrylamide (
HbAA) and glycidamide (HbGA) in 801 non-smoking postmenopausal women
from eight countries in the European Prospective Investigation into
Cancer and Nutrition (EPIC) cohort.
Methods Biomarkers of internal exposure were measured in red blood cells
(collected at baseline) by high-performance liquid chromatography/tandem
mass spectrometry (HPLC/MS/MS). In this cross-sectional analysis, four
dependent variables were evaluated: HbAA, HbGA, sum of total adducts
(HbAA + HbGA), and their ratio (HbGA/HbAA). Simple and multiple
regression analyses were used to identify determinants of the four
outcome variables. All dependent variables (except HbGA/HbAA) and all
independent variables were log-transformed (log2) to improve normality.
Median (25th-75th percentile) HbAA and HbGA adduct levels were 41.3
(32.8-53.1) pmol/g Hb and 34.2 (25.4-46.9) pmol/g Hb, respectively.
Results The main food group determinants of HbAA, HbGA, and HbAA + HbGA
were biscuits, crackers, and dry cakes. Alcohol intake and body mass
index were identified as the principal determinants of HbGA/HbAA. The
total percent variation in HbAA, HbGA, HbAA + HbGA, and HbGA/HbAA
explained in this study was 30, 26, 29, and 13 %, respectively.
Conclusions Dietary and lifestyle factors explain a moderate proportion
of acrylamide adduct variation in nonsmoking postmenopausal women from
the EPIC cohort
An epidemiological model for prediction of endometrial cancer risk in Europe
Endometrial cancer (EC) is the fourth most frequent cancer in women in
Europe, and as its incidence is increasing, prevention strategies gain
further pertinence. Risk prediction models can be a useful tool for
identifying women likely to benefit from targeted prevention measures.
On the basis of data from 201,811 women (mostly aged 30-65 years)
including 855 incident EC cases from eight countries in the European
Prospective Investigation into Cancer and Nutrition cohort, a model to
predict EC was developed. A step-wise model selection process was used
to select confirmed predictive epidemiologic risk factors. Piece-wise
constant hazard rates in 5-year age-intervals were estimated in a
cause-specific competing risks model, five-fold-cross-validation was
applied for internal validation. Risk factors included in the risk
prediction model were body-mass index (BMI), menopausal status, age at
menarche and at menopause, oral contraceptive use, overall and by
different BMI categories and overall duration of use, parity, age at
first full-term pregnancy, duration of menopausal hormone therapy and
smoking status (specific for pre, peri- and post-menopausal women).
These variables improved the discriminating capacity to predict risk
over 5 years from 71 % for a model based on age alone to 77 % (overall
C statistic), and the model was well-calibrated (ratio of expected to
observed cases = 0.99). Our model could be used for the identification
of women at increased risk of EC in Western Europe. To achieve an
EC-risk model with general validity, a large-scale cohort-consortium
approach would be needed to assess and adjust for population variation
Acrylamide and glycidamide hemoglobin adduct levels and endometrial cancer risk: A nested case-control study in nonsmoking postmenopausal women from the EPIC cohort
Acrylamide, classified in 1994 by IARC as “probably carcinogenic to
humans,” was discovered in 2002 in some heat-treated,
carbohydrate-rich foods. Four prospective studies have evaluated the
association between dietary acrylamide intake and endometrial cancer
(EC) risk with inconsistent results. The purpose of this nested
case-control study, based on the European Prospective Investigation into
Cancer and Nutrition (EPIC) cohort, was to evaluate, for the first time,
the association between hemoglobin adducts of acrylamide (HbAA) and
glycidamide (HbGA) and the risk of developing EC in non-smoking
postmenopausal women. Hemoglobin adducts were measured in red blood
cells by HPLC/MS/MS. Four exposure variables were evaluated: HbAA, HbGA,
their sum (HbAA1HbGA), and their ratio (HbGA/HbAA). The association
between hemoglobin adducts and EC was evaluated using unconditional
multivariable logistic regression models, and included 383 EC cases (171
were type-I EC), and 385 controls. Exposure variables were analyzed in
quintiles based on control distributions. None of the biomarker
variables had an effect on overall EC (HRHbAA;Q5vsQ1: 0.84, 95% CI:
0.49-1.48; HRHbGA;Q5vsQ1: 0.94, 95% CI: 0.54-1.63) or type-I EC risk.
Additionally, none of the subgroups investigated (BMI < 25 vs. >= 25 kg
m 22, alcohol drinkers vs. never drinkers, oral contraceptive users vs.
non-users) demonstrated effect measure modification. Hemoglobin adducts
of acrylamide or glycidamide were not associated with EC or type-I EC
risk in 768 nonsmoking postmenopausal women from the EPIC cohort
Acrylamide and Glycidamide Hemoglobin Adducts and Epithelial Ovarian Cancer: A Nested Case-Control Study in Nonsmoking Postmenopausal Women from the EPIC Cohort
Background: Acrylamide was classified as “probably carcinogenic to
humans (group 2A)” by the International Agency for Research on
Cancer. Epithelial ovarian cancer (EOC) is the fourth cause of cancer
mortality in women. Five epidemiological studies have evaluated the
association between EOC risk and dietary acrylamide intake assessed
using food frequency questionnaires, and one nested case-control study
evaluated hemoglobin adducts of acrylamide (HbAA) and its metabolite
glycidamide (HbGA) and EOC risk; the results of these studies were
inconsistent.
Methods: A nested case-control study in nonsmoking postmenopausal women
(334 cases, 417 controls) was conducted within the European Prospective
Investigation into Cancer and Nutrition (EPIC) cohort. Unconditional
logistic regression models were used to estimate ORs and 95% confidence
intervals (CI) for the association between HbAA, HbGA, HbAA+HbGA, and
HbGA/HbAA and EOC and invasive serous EOC risk.
Results: No overall associations were observed between biomarkers of
acrylamide exposure analyzed in quintiles and EOC risk; however,
positive associations were observed between some middle quintiles of
HbGA and HbAA+HbGA. Elevated but non-statistically significant ORs for
serous EOC were observed for HbGA and HbAA+HbGA (ORQ5vsQ1, 1.91; 95%
CI, 0.96-3.81 and ORQ5vsQ1, 1.90; 95% CI, 0.94-3.83, respectively);
however, no linear dose-response trends were observed.
Conclusion: This EPIC nested case-control study failed to observe a
clear association between biomarkers of acrylamide exposure and the risk
of EOC or invasive serous EOC.
Impact: It is unlikely that dietary acrylamide exposure increases
ovarian cancer risk; however, additional studies with larger sample size
should be performed to exclude any possible association with EOC risk.
(C) 2015 AACR
Dietary intake of acrylamide and esophageal cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort
The relation between dietary acrylamide intake and esophageal cancer
(EC) risk, including esophageal adenocarcinoma (EAC) and esophageal
squamous cell carcinoma (ESCC), has not been consistent. We evaluated
the association between dietary acrylamide intake and EAC, ESCC, and
overall EC in the European Prospective Investigation into Cancer and
Nutrition (EPIC) cohort.
Multivariate Cox proportional hazards models were used to estimate the
HR and 95 % confidence interval (95 % CI). Since nonlinear relations
were observed, HRs were displayed for quartiles of acrylamide intake in
mu g per day.
After a mean follow-up of 11 years, 341 EC were identified, 142 of which
were EAC, 176 ESCC, and 23 other histological types or not specified. An
increase in EC risk was observed in the second and third quartiles
(HRQ2vsQ1 1.75, 95 % CI 1.12-2.74; HRQ3vsQ1 1.66, 95 % CI 1.05-2.61),
but not in the fourth quartile, and there was no evidence for a linear
dose-response trend. HRs were similarly elevated but not statistically
significant when ESCC and EAC were analyzed separately, due to the small
number of cases observed. No associations were observed when quartiles
were based on energy-adjusted acrylamide intake.
In the EPIC cohort, an association between estimated dietary acrylamide
intake and an increased risk of developing EC was observed in the middle
quartiles but not in the highest quartile; however, results from other
larger cohorts or consortia, and results from biomarker studies, might
add to the evidence provided by this analysis, suggesting that
acrylamide is not an important risk factor for EC
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Flavonoid and lignan intake and pancreatic cancer risk in the European prospective investigation into cancer and nutrition cohort.
Despite the potential cancer preventive effects of flavonoids and lignans, their ability to reduce pancreatic cancer risk has not been demonstrated in epidemiological studies. Our aim was to examine the association between dietary intakes of flavonoids and lignans and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 865 exocrine pancreatic cancer cases occurred after 11.3 years of follow-up of 477,309 cohort members. Dietary flavonoid and lignan intake was estimated through validated dietary questionnaires and the US Department of Agriculture (USDA) and Phenol Explorer databases. Hazard ratios (HR) and 95% confidence intervals (CIs) were calculated using age, sex and center-stratified Cox proportional hazards models, adjusted for energy intake, body mass index (BMI), smoking, alcohol and diabetes status. Our results showed that neither overall dietary intake of flavonoids nor of lignans were associated with pancreatic cancer risk (multivariable-adjusted HR for a doubling of intake = 1.03, 95% CI: 0.95-1.11 and 1.02; 95% CI: 0.89-1.17, respectively). Statistically significant associations were also not observed by flavonoid subclasses. An inverse association between intake of flavanones and pancreatic cancer risk was apparent, without reaching statistical significance, in microscopically confirmed cases (HR for a doubling of intake = 0.96, 95% CI: 0.91-1.00). In conclusion, we did not observe an association between intake of flavonoids, flavonoid subclasses or lignans and pancreatic cancer risk in the EPIC cohort
Endogenous androgens and risk of epithelial invasive ovarian cancer by tumor characteristics in the European Prospective Investigation into Cancer and Nutrition
The role of endogenous androgens and sex hormone-binding globulin (SHBG)
in ovarian carcinogenesis is poorly understood. Epithelial invasive
ovarian cancer (EOC) is a heterogeneous disease and there are no
prospective data on endogenous androgens and EOC risk by tumor
characteristics (histology, grade, stage) or the dualistic model of
ovarian carcinogenesis (i.e. type I vs. type II, leading to less or more
aggressive tumors). We conducted a nested case-control study in the
European Prospective Investigation into Cancer and Nutrition (EPIC)
cohort evaluating androgens and SHBG and invasive EOC risk by tumor
characteristics. Female participants who provided a blood sample and
were not using exogenous hormones at blood donation were eligible (n =
183,257). A total of 565 eligible women developed EOC; two controls (n =
1,097) were matched per case. We used multivariable conditional logistic
regression models. We observed no association between androgens, SHBG
and EOC overall. A doubling of androstenedione reduced risk of serous
carcinomas by 21% (odds ratio (OR)log2=0.79, 95% confidence interval
[CI]=[0.64-0.97]). Moreover, associations differed for low-grade and
high-grade carcinomas, with positive associations for low-grade and
inverse associations for high-grade carcinomas (e.g. androstenedione:
low grade: ORlog2=1.99 [0.98-4.06]; high grade: ORlog2=0.75
[0.61-0.93], p(het)0.01), similar associations were observed for type
I/II tumors. This is the first prospective study to evaluate androgens,
SHBG and EOC risk by tumor characteristics and type I/II status. Our
findings support a possible role of androgens in ovarian carcinogenesis.
Additional studies exploring this association are needed.
What’s new? There appear to be several types of epithelial invasive
ovarian cancer (EOC), and hormone-related risk factors are poorly
understood. In this study, the authors found that the impact of
endogenous androgens on the risk of developing EOC differed depending
upon tumor characteristics. Androgen concentrations were positively
associated with the risk of low-grade and type-I carcinomas, but the
study found an inverse association for high-grade tumors. These findings
support a possible role for androgens in ovarian carcinogenesis, and
emphasize the need for additional research
Dietary Intake of Acrylamide and Epithelial Ovarian Cancer Risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) Cohort
Acrylamide, classified in 1994 by the International Agency for Research
on Cancer (IARC) as “probably carcinogenic” to humans, was
discovered in 2002 in some heat-treated, carbohydrate-rich foods. The
association between dietary acrylamide intake and epithelial ovarian
cancer risk (EOC) has been previously studied in one case-control and
three prospective cohort studies which obtained inconsistent results and
could not further examine histologic subtypes other than serous EOC. The
present study was carried out in the European Prospective Investigation
into Cancer and Nutrition (EPIC) subcohort of women (n = 325,006).
Multivariate Cox proportional hazards models were used to assess the
association between questionnaire-based acrylamide intake and EOC risk.
Acrylamide was energy-adjusted using the residual method and was
evaluated both as a continuous variable (per 10 mu g/d) and in
quintiles; when subgroups by histologic EOC subtypes were analyzed,
acrylamide intake was evaluated in quartiles. During a mean follow-up of
11 years, 1,191 incident EOC cases were diagnosed. At baseline, the
median acrylamide intake in EPIC was 21.3 mu g/d. No associations and no
evidence for a dose-response were observed between energy-adjusted
acrylamide intake and EOC risk (HR10 mu(g/d), 1.02; 95% CI, 0.96-1.09;
HRQ5vsQ1, 0.97; 95% CI, 0.76-1.23). No differences were seen when
invasive EOC subtypes (582 serous, 118 endometrioid, and 79 mucinous
tumors) were analyzed separately. This study did not provide evidence
that acrylamide intake, based on food intake questionnaires, was
associated with risk for EOC in EPIC. Additional studies with more
reliable estimates of exposure based on biomarkers may be needed. (C)
2014 AACR