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.

• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• nádory slinivky břišní epidemiologie   MeSH
• pohybová aktivita * MeSH
• rizikové faktory MeSH
• sběr dat MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• volnočasové aktivity MeSH
• zaměstnání MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Geografické názvy
• Česká republika MeSH
• Slovenská republika MeSH

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.

• MeSH
• dospělí MeSH
• index tělesné hmotnosti * MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• nádory slinivky břišní * epidemiologie   MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• tělesná hmotnost MeSH
• velikost těla * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Geografické názvy
• Česká republika MeSH
• Slovenská republika MeSH

The utility of KRAS mutations in plasma circulating cell-free DNA (cfDNA) samples as non-invasive biomarkers for the detection of pancreatic cancer has never been evaluated in a large case-control series. We applied a KRAS amplicon-based deep sequencing strategy combined with analytical pipeline specifically designed for the detection of low-abundance mutations to screen plasma samples of 437 pancreatic cancer cases, 141 chronic pancreatitis subjects, and 394 healthy controls. We detected mutations in 21.1% (N=92) of cases, of whom 82 (89.1%) carried at least one mutation at hotspot codons 12, 13 or 61, with mutant allelic fractions from 0.08% to 79%. Advanced stages were associated with an increased proportion of detection, with KRAS cfDNA mutations detected in 10.3%, 17,5% and 33.3% of cases with local, regional and systemic stages, respectively. We also detected KRAS cfDNA mutations in 3.7% (N=14) of healthy controls and in 4.3% (N=6) of subjects with chronic pancreatitis, but at significantly lower allelic fractions than in cases. Combining cfDNA KRAS mutations and CA19-9 plasma levels on a limited set of case-control samples did not improve the overall performance of the biomarkers as compared to CA19-9 alone. Whether the limited sensitivity and specificity observed in our series of KRAS mutations in plasma cfDNA as biomarkers for pancreatic cancer detection are attributable to methodological limitations or to the biology of cfDNA should be further assessed in large case-control series.

• MeSH
• antigen CA-19-9 krev   MeSH
• cirkulující nádorová DNA krev   genetika   MeSH
• duktální karcinom pankreatu krev   genetika   patologie   MeSH
• fenotyp MeSH
• frekvence genu MeSH
• genetická predispozice k nemoci MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace * MeSH
• mutační analýza DNA MeSH
• nádorové biomarkery krev   genetika   MeSH
• nádory slinivky břišní krev   genetika   patologie   MeSH
• pilotní projekty MeSH
• prediktivní hodnota testů MeSH
• protoonkogenní proteiny p21(ras) krev   genetika   MeSH
• reprodukovatelnost výsledků MeSH
• senioři MeSH
• staging nádorů MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• validační studie MeSH
• Geografické názvy
• Česká republika MeSH
• Slovenská republika MeSH

BACKGROUND: The DNA released into the bloodstream by malignant tumours· called circulating tumour DNA (ctDNA), is often a small fraction of total cell-free DNA shed predominantly by hematopoietic cells and is therefore challenging to detect. Understanding the biological properties of ctDNA is key to the investigation of its clinical relevance as a non-invasive marker for cancer detection and monitoring. METHODS: We selected 40 plasma DNA samples of pancreatic cancer cases previously reported to carry a KRAS mutation at the 'hotspot' codon 12 and re-screened the cell-free DNA using a 4-size amplicons strategy (57 bp, 79 bp, 167 bp and 218 bp) combined with ultra-deep sequencing in order to investigate whether amplicon lengths could impact on the capacity of detection of ctDNA, which in turn could provide inference of ctDNA and non-malignant cell-free DNA size distribution. FINDINGS: Higher KRAS amplicon size (167 bp and 218 bp) was associated with lower detectable cell-free DNA mutant allelic fractions (p < 0·0001), with up to 4·6-fold (95% CI: 2·6-8·1) difference on average when comparing the 218bp- and the 57bp-amplicons. The proportion of cases with detectable KRAS mutations was also hampered with increased amplicon lengths, with only half of the cases having detectable ctDNA using the 218 bp assay relative to those detected with amplicons less than 80 bp. INTERPRETATION: Tumour-derived mutations are carried by shorter cell-free DNA fragments than fragments of wild-type allele. Targeting short amplicons increases the sensitivity of cell-free DNA assays for pancreatic cancer and should be taken into account for optimized assay design and for evaluating their clinical performance. FUNDING: IARC; MH CZ - DRO; MH SK; exchange program between IARC and Sao Paulo medical Sciences; French Cancer League.

• MeSH
• alely MeSH
• chronická pankreatitida krev   diagnóza   genetika   patologie   MeSH
• cirkulující nádorová DNA krev   genetika   MeSH
• exprese genu MeSH
• frekvence genu MeSH
• kodon MeSH
• lidé MeSH
• mutace MeSH
• nádorové biomarkery krev   genetika   MeSH
• nádory slinivky břišní krev   diagnóza   genetika   patologie   MeSH
• protoonkogenní proteiny p21(ras) krev   genetika   MeSH
• sekvence nukleotidů MeSH
• senzitivita a specificita MeSH
• studie případů a kontrol MeSH
• výpočetní biologie MeSH
• vysoce účinné nukleotidové sekvenování metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH