IMPORTANCE: Cigarette smoking is a strong risk factor for mortality in patients diagnosed with head and neck squamous cell carcinoma (HNSCC). However, little evidence supports which smoking metric best models the association between smoking and survival in HNSCC. OBJECTIVE: To determine which smoking metric best models a linear association between smoking exposure and overall survival (OS) in patients with HNSCC. DESIGN, SETTING, AND PARTICIPANTS: A retrospective multicenter cohort study of 6 clinical epidemiological studies was performed. Five were part of the Human Papillomavirus, Oral and Oropharyngeal Cancer Genomic Research (VOYAGER) consortium. Participants included patients 18 years and older with pathologically confirmed HNSCC. Data were collected from January 2002 to December 2019, and data were analyzed between January 2022 to November 2024. MAIN OUTCOMES AND MEASURES: The primary outcome was OS. The performance of 8 smoking metrics, including pack-years, duration, and log cig-years (calculated as log10[cigarettes smoked per day + 1] × number of years smoked) for modeling OS were compared. Metric performance was measured by the strength of association in Cox proportional hazard models, linearity based on P for linear trend, Akaike information criterion (AIC; lower value indicates better model fit), and visual assessment of spline curves. Secondary outcomes included modeling OS in clinicodemographic subgroups and HNSCC anatomic subsites. Exploratory outcomes included cancer-specific survival and noncancer survival. RESULTS: In total, 8875 patients with HNSCC (2114 [24%] female; median [IQR] age, 61 [54-69] years) were included. Of 8 smoking metrics evaluated, smoking duration (adjusted hazard ratio [aHR], 1.11 [95% CI, 1.03-1.19]) and log cig-years (aHR, 1.11 [95% CI, 1.04-1.18]) had the highest aHRs; both had a statistically significant linear association with OS. Log cig-years had the lowest AIC linear value and the most visually linear spline curve when modeling OS. Duration and log cig-years outperformed pack-years for modeling OS regardless of age, smoking status, and cancer stage. Both performed well in lip and oral cavity, laryngeal (only duration was significant), and human papillomavirus-negative oropharyngeal subsites. In an exploratory analysis, duration had the highest aHR (1.15 [95% CI, 1.02-1.29]), and log cig-years had the lowest AIC linear value when modeling noncancer survival. CONCLUSIONS AND RELEVANCE: In this cohort study, smoking duration and log cig-years best modeled a linear relationship with OS for patients with HNSCC. Both metrics maintained robust performance within specific clinicodemographic subgroups and anatomic subsites. Although most HNSCC survival models control for smoking exposure using smoking status or pack-years, duration and log cig-years may be superior metrics to account for the effects of smoking on survival.
- MeSH
- dlaždicobuněčné karcinomy hlavy a krku * mortalita MeSH
- kouření cigaret * škodlivé účinky MeSH
- kouření * škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- míra přežití MeSH
- nádory hlavy a krku * mortalita MeSH
- proporcionální rizikové modely MeSH
- retrospektivní studie MeSH
- rizikové faktory MeSH
- senioři 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
Biological mechanisms related to cancer development can leave distinct molecular fingerprints in tumours. By leveraging multi-omics and epidemiological information, we can unveil relationships between carcinogenesis processes that would otherwise remain hidden. Our integrative analysis of DNA methylome, transcriptome, and somatic mutation profiles of kidney tumours linked ageing, epithelial-mesenchymal transition (EMT), and xenobiotic metabolism to kidney carcinogenesis. Ageing process was represented by associations with cellular mitotic clocks such as epiTOC2, SBS1, telomere length, and PBRM1 and SETD2 mutations, which ticked faster as tumours progressed. We identified a relationship between BAP1 driver mutations and the epigenetic upregulation of EMT genes (IL20RB and WT1), correlating with increased tumour immune infiltration, advanced stage, and poorer patient survival. We also observed an interaction between epigenetic silencing of the xenobiotic metabolism gene GSTP1 and tobacco use, suggesting a link to genotoxic effects and impaired xenobiotic metabolism. Our pan-cancer analysis showed these relationships in other tumour types. Our study enhances the understanding of kidney carcinogenesis and its relation to risk factors and progression, with implications for other tumour types.
- MeSH
- DNA vazebné proteiny genetika metabolismus MeSH
- epigeneze genetická MeSH
- epitelo-mezenchymální tranzice * genetika MeSH
- glutathion-S-transferasa fí genetika metabolismus MeSH
- histonlysin-N-methyltransferasa genetika metabolismus MeSH
- karcinogeneze * genetika MeSH
- lidé MeSH
- metylace DNA * MeSH
- multiomika MeSH
- mutace * MeSH
- nádorové supresorové proteiny genetika metabolismus MeSH
- nádory ledvin * genetika patologie MeSH
- regulace genové exprese u nádorů MeSH
- stárnutí genetika MeSH
- thiolesterasa ubikvitinu MeSH
- transkripční faktory genetika metabolismus MeSH
- transkriptom MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
International differences in the incidence of many cancer types indicate the existence of carcinogen exposures that have not yet been identified by conventional epidemiology make a substantial contribution to cancer burden1. In clear cell renal cell carcinoma, obesity, hypertension and tobacco smoking are risk factors, but they do not explain the geographical variation in its incidence2. Underlying causes can be inferred by sequencing the genomes of cancers from populations with different incidence rates and detecting differences in patterns of somatic mutations. Here we sequenced 962 clear cell renal cell carcinomas from 11 countries with varying incidence. The somatic mutation profiles differed between countries. In Romania, Serbia and Thailand, mutational signatures characteristic of aristolochic acid compounds were present in most cases, but these were rare elsewhere. In Japan, a mutational signature of unknown cause was found in more than 70% of cases but in less than 2% elsewhere. A further mutational signature of unknown cause was ubiquitous but exhibited higher mutation loads in countries with higher incidence rates of kidney cancer. Known signatures of tobacco smoking correlated with tobacco consumption, but no signature was associated with obesity or hypertension, suggesting that non-mutagenic mechanisms of action underlie these risk factors. The results of this study indicate the existence of multiple, geographically variable, mutagenic exposures that potentially affect tens of millions of people and illustrate the opportunities for new insights into cancer causation through large-scale global cancer genomics.
- MeSH
- genom lidský genetika MeSH
- genomika MeSH
- hypertenze epidemiologie MeSH
- incidence MeSH
- karcinom z renálních buněk * genetika epidemiologie chemicky indukované MeSH
- kouření tabáku škodlivé účinky genetika MeSH
- kyseliny aristolochové škodlivé účinky MeSH
- lidé MeSH
- mutace * MeSH
- mutageny * škodlivé účinky MeSH
- nádory ledvin * genetika epidemiologie chemicky indukované MeSH
- obezita epidemiologie MeSH
- rizikové faktory MeSH
- vystavení vlivu životního prostředí * škodlivé účinky analýza MeSH
- zeměpis * MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Geografické názvy
- Japonsko MeSH
- Rumunsko MeSH
- Srbsko MeSH
- Thajsko MeSH
Here, in a multi-ancestry genome-wide association study meta-analysis of kidney cancer (29,020 cases and 835,670 controls), we identified 63 susceptibility regions (50 novel) containing 108 independent risk loci. In analyses stratified by subtype, 52 regions (78 loci) were associated with clear cell renal cell carcinoma (RCC) and 6 regions (7 loci) with papillary RCC. Notably, we report a variant common in African ancestry individuals ( rs7629500 ) in the 3' untranslated region of VHL, nearly tripling clear cell RCC risk (odds ratio 2.72, 95% confidence interval 2.23-3.30). In cis-expression quantitative trait locus analyses, 48 variants from 34 regions point toward 83 candidate genes. Enrichment of hypoxia-inducible factor-binding sites underscores the importance of hypoxia-related mechanisms in kidney cancer. Our results advance understanding of the genetic architecture of kidney cancer, provide clues for functional investigation and enable generation of a validated polygenic risk score with an estimated area under the curve of 0.65 (0.74 including risk factors) among European ancestry individuals.
- MeSH
- běloši genetika MeSH
- celogenomová asociační studie * MeSH
- genetická predispozice k nemoci * MeSH
- jednonukleotidový polymorfismus * MeSH
- karcinom z renálních buněk * genetika MeSH
- lidé MeSH
- lokus kvantitativního znaku * MeSH
- nádorový supresorový protein VHL genetika MeSH
- nádory ledvin * genetika MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- MeSH
- hodnocení výsledků péče pacientem MeSH
- lidé MeSH
- mladiství MeSH
- pití nezletilých MeSH
- stravovací zvyklosti klasifikace MeSH
- zdravotně rizikové chování klasifikace MeSH
- zdravý životní styl klasifikace MeSH
- životní styl * MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Klíčová slova
- dotazníkový průzkum, recenzovaný článek,
- MeSH
- antikoncepce MeSH
- Romové MeSH
- znalosti MeSH
Táto práca analyzuje súčasný stav využitia biometrie v počítačovej bezpečnosti. Ponúka prehľad najčastejšie používaných anatomicko-fyziologických a behaviorálnych biometrických identifi kačných metód. Výsledkom práce by mal byť nový komplex metód, ktorý umožní spoľahlivú identifi káciu užívateľa čo najkomfortnejšou formou. Výsledná aplikácia nových princípov zabezpečenia bude použitá pre zvýšenie ochrany špecializovaného zdravotného záznamu. Ďalej dôjde k rozšíreniu obecne pojatého konceptu EHR MUDR do ďalšej aplikačnej oblasti.
- MeSH
- jazyk (prostředek komunikace) MeSH
- kontinuální vzdělávání zdravotních sester trendy MeSH
- kulturní různorodost MeSH
- lidé MeSH
- mezinárodní spolupráce MeSH
- Check Tag
- lidé MeSH
- Geografické názvy
- Norsko MeSH
