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Bosetti C.,Istituto di Ricerche Farmacologiche Mario Negri | Rosato V.,Istituto di Ricerche Farmacologiche Mario Negri | Li D.,University of Texas M. D. Anderson Cancer Center | Silverman D.,National Cancer Institute | And 35 more authors.
Annals of oncology : official journal of the European Society for Medical Oncology / ESMO | Year: 2014

BACKGROUND: Type 2 diabetes mellitus has been associated with an excess risk of pancreatic cancer, but the magnitude of the risk and the time-risk relationship are unclear, and there is limited information on the role of antidiabetic medications.PATIENTS AND METHODS: We analyzed individual-level data from 15 case-control studies within the Pancreatic Cancer Case-Control Consortium, including 8305 cases and 13 987 controls. Pooled odds ratios (ORs) were estimated from multiple logistic regression models, adjusted for relevant covariates.RESULTS: Overall, 1155 (15%) cases and 1087 (8%) controls reported a diagnosis of diabetes 2 or more years before cancer diagnosis (or interview, for controls), corresponding to an OR of 1.90 (95% confidence interval, CI, 1.72-2.09). Consistent risk estimates were observed across strata of selected covariates, including body mass index and tobacco smoking. Pancreatic cancer risk decreased with duration of diabetes, but a significant excess risk was still evident 20 or more years after diabetes diagnosis (OR 1.30, 95% CI 1.03-1.63). Among diabetics, long duration of oral antidiabetic use was associated with a decreased pancreatic cancer risk (OR 0.31, 95% CI 0.14-0.69, for ≥15 years). Conversely, insulin use was associated with a pancreatic cancer risk in the short term (OR 5.60, 95% CI 3.75-8.35, for <5 years), but not for longer duration of use (OR 0.95, 95% CI 0.53-1.70, for ≥15 years).CONCLUSION: This study provides the most definitive quantification to date of an excess risk of pancreatic cancer among diabetics. It also shows that a 30% excess risk persists for more than two decades after diabetes diagnosis, thus supporting a causal role of diabetes in pancreatic cancer. Oral antidiabetics may decrease the risk of pancreatic cancer, whereas insulin showed an inconsistent duration-risk relationship. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com. Source


Li P.,International Agency for Research on Cancer | Znaor A.,International Agency for Research on Cancer | Holcatova I.,Charles University | Fabianova E.,Regional Authority of Public Health in Banska Bystrica | And 4 more authors.
European Urology | Year: 2015

Context Marked unexplained national variations in incidence rates of kidney cancer have been observed for decades in Europe. Objective To investigate geographic variations at the regional level and identify European regions with high incidence rates of kidney cancer. Evidence acquisition Regional- and national-level incidence data were extracted from the Cancer Incidence in Five Continents databases, local cancer registry databases, and local published reports. World population age-standardised rates (ASRs) were calculated for the periods 2003-2007 and 1988-1992. Rates by period and sex were compared using map visualisation. Evidence synthesis During 2003-2007, the highest ASR was found in the Plzen region, Czech Republic (31.4/100 000 person-years in men). Other regions of the Czech Republic had ASRs of 18.6-27.5/100 000 in men, with a tendency for higher rates in regions south of Prague. Surrounding regions, including eastern Germany and regions of Slovakia and Austria, had medium-to-high incidence rates (13.0-16.8/100 000 in men). Three other areas in Europe showed higher incidence rates in men compared with the rest of the continent: Lithuania, Estonia, Latvia, and Belarus (15.0-17.6/100 000); Iceland (13.5/100 000), and northern Italy (up to 16.0/100 000). Similar regional differences were observed among women, with rates approximately half of those observed in men in the same region. In general, these regional geographic variations remained stable over the periods 1988-1992 and 2003-2007, although higher incidence rates were detected in the Baltic countries in 2003-2007. Conclusions Several European regions show particularly high rates of kidney cancer incidence. Large variations were observed within countries covered by national health-care systems, implying that overdetection is not the major factor. Patient summary We present regional geographic variations in kidney cancer incidence rates in Europe. We highlight several regions with high incidence rates where further studies should be conducted for cancer control and prevention. © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved. Source


Brenner D.R.,International Agency for Research on Cancer IARC | Wozniak M.B.,International Agency for Research on Cancer IARC | Feyt C.,International Agency for Research on Cancer IARC | Holcatova I.,Charles University | And 10 more authors.
Cancer Causes and Control | Year: 2014

Purpose: Findings from epidemiological studies examining physical activity in relation to pancreatic cancer risk have suggested decreased risks for physical activity; however, the results are inconsistent. Methods: The association between occupational and leisure-time physical activity and risk of pancreatic cancer was examined among 826 pancreatic cancer cases and 930 age-, sex- and center-matched controls from a large multicenter central European study in Czech Republic and Slovakia recruited between 2004 and 2012. Data on physical activity including type and dose (frequency, intensity, and duration) were examined using multivariable-adjusted logistic regression models. Results: Occupational physical activity was not significantly associated with risk of pancreatic cancer [odds ratio (OR) 0.90, 95 % confidence interval (CI) 0.71-1.15]. A 35 % decrease in risk of pancreatic cancer was observed for regular leisure-time physical activity (OR 0.65, 95 % CI 0.52-0.87). The risk estimates were significant for low and moderate intensity of activity with the strongest protective effect among individuals who exercised during more than 40 weeks per year. The results for cumulated leisure-time physical activity assessed 1 year prior to diagnosis achieved the same level of risk reduction. In addition, stronger risk estimates for leisure-time physical activity were observed among women (men: OR 0.74, 95 % CI 0.54-1.01; women: OR 0.53, 95 % CI 0.37-0.75). The findings for female participants were stronger for intensity and frequency of leisure-time physical activity, in particular for light and moderate activity (OR 0.43, 95 % CI 0.25-0.75; and OR 0.57, 95 % CI 0.37-0.88, respectively). Conclusion: These results provide evidence for a decreased risk of pancreatic cancer associated with regular leisure-time physical activity. © 2014 Springer International Publishing Switzerland. Source


Urayama K.Y.,International Agency for Research on Cancer | Holcatova I.,Charles University | Janout V.,Palacky University | Foretova L.,Masaryk Memorial Cancer Institute | And 6 more authors.
International Journal of Cancer | Year: 2011

The relationship between two measures of excess body weight, body mass index (BMI) and body size score, and risk of pancreatic cancer was examined among 574 pancreatic cancer cases and 596 frequency-matched controls from the Czech Republic and Slovakia enrolled between 2004 and 2009. Analyses using multivariable logistic regression showed an increased risk of pancreatic cancer associated with elevated quartiles of BMI at ages 20 [fourth quartile: odds ratio (OR) = 1.79, 95% confidence interval (CI): 1.23, 2.61] and 40 (fourth quartile: OR = 1.57, 95% CI: 1.09, 2.27) compared to the lowest quartile. Consistent results were observed for body size score at ages 20 (high versus low: OR = 1.66, 95% CI: 1.08, 2.57) and 40 (medium versus low: OR = 1.36, 95% CI: 1.00, 1.86), but no association was found for BMI and body size score at 2 years before the interview. Stronger risk estimates for BMI were observed in males than females, particularly at age 20, but the analysis of body size yielded similar estimates by sex. When considering excess body weight at both ages 20 and 40 jointly, the highest risk estimates were observed among subjects with elevated levels at both time periods in the analysis of BMI (OR = 1.86, 95% CI: 1.32, 2.62) and body size (OR = 1.53, 95% CI: 1.09, 2.13). These findings, based on two different measures, provide strong support for an increased risk of pancreatic cancer associated with excess body weight, possibly strongest during early adulthood. Copyright © 2011 UICC. Source


Lips E.H.,International Agency for Research on Cancer IARC | Gaborieau V.,International Agency for Research on Cancer IARC | McKay J.D.,International Agency for Research on Cancer IARC | Chabrier A.,International Agency for Research on Cancer IARC | And 48 more authors.
International Journal of Epidemiology | Year: 2010

Background: Genetic variants in 15q25 have been identified as potential risk markers for lung cancer (LC), but controversy exists as to whether this is a direct association, or whether the 15q variant is simply a proxy for increased exposure to tobacco carcinogens. Methods: We performed a detailed analysis of one 15q single nucleotide polymorphism (SNP) (rs16969968) with smoking behaviour and cancer risk in a total of 17 300 subjects from five LC studies and four upper aerodigestive tract (UADT) cancer studies. Results: Subjects with one minor allele smoked on average 0.3 cigarettes per day (CPD) more, whereas subjects with the homozygous minor AA genotype smoked on average 1.2 CPD more than subjects with a GG genotype (P<0.001). The variant was associated with heavy smoking (>20 CPD) [odds ratio (OR)=1.13, 95% confidence interval (CI) 0.96-1.34, P=0.13 for heterozygotes and 1.81, 95% CI 1.39-2.35 for homozygotes, P<0.0001]. The strong association between the variant and LC risk (OR=1.30, 95% CI 1.23-1.38, P = 1 × 10-18), was virtually unchanged after adjusting for this smoking association (smoking adjusted OR=1.27, 95% CI 1.19-1.35, P=5 × 10-13). Furthermore, we found an association between the variant allele and an earlier age of LC onset (P=0.02). The association was also noted in UADT cancers (OR=1.08, 95% CI 1.01-1.15, P=0.02). Genome wide association (GWA) analysis of over 300 000 SNPs on 11 219 subjects did not identify any additional variants related to smoking behaviour. Conclusions This study confirms the strong association between 15q gene variants and LC and shows an independent association with smoking quantity, as well as an association with UADT cancers. © Published by Oxford University Press on behalf of the International Epidemiological Association. The Author 2009; all rights reserved. Source

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