Browsing by Subject "SMOKING"

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  • Surakka, Ida; Isaacs, Aaron; Karssen, Lennart C.; Laurila, Pirkka-Pekka P.; Middelberg, Rita P. S.; Tikkanen, Emmi; Ried, Janina S.; Lamina, Claudia; Mangino, Massimo; Igl, Wilmar; Hottenga, Jouke-Jan; Lagou, Vasiliki; van der Harst, Pim; Leach, Irene Mateo; Esko, Tonu; Kutalik, Zoltan; Wainwright, Nicholas W.; Struchalin, Maksim V.; Sarin, Antti-Pekka; Kangas, Antti J.; Viikari, Jorma S.; Perola, Markus; Rantanen, Taina; Petersen, Ann-Kristin; Soininen, Pasi; Johansson, Asa; Soranzo, Nicole; Heath, Andrew C.; Papamarkou, Theodore; Prokopenko, Inga; Toenjes, Anke; Kronenberg, Florian; Doering, Angela; Rivadeneira, Fernando; Montgomery, Grant W.; Whitfield, John B.; Kahonen, Mika; Lehtimaki, Terho; Freimer, Nelson B.; Willemsen, Gonneke; de Geus, Eco J. C.; Palotie, Aarno; Sandhu, Manj S.; Waterworth, Dawn M.; Metspalu, Andres; Stumvoll, Michael; Uitterlinden, Andre G.; Jula, Antti; Navis, Gerjan; Wijmenga, Cisca; Wolffenbuttel, Bruce H. R.; Taskinen, Marja-Riitta; Ala-Korpela, Mika; Kaprio, Jaakko; Kyvik, Kirsten O.; Boomsma, Dorret I.; Pedersen, Nancy L.; Gyllensten, Ulf; Wilson, James F.; Rudan, Igor; Campbell, Harry; Pramstaller, Peter P.; Spector, Tim D.; Witteman, Jacqueline C. M.; Eriksson, Johan G.; Salomaa, Veikko; Oostra, Ben A.; Raitakari, Olli T.; Wichmann, H. -Erich; Gieger, Christian; Jaervelin, Marjo-Riitta; Martin, Nicholas G.; Hofman, Albert; McCarthy, Mark I.; Palotie, Leena; van Duijn, Cornelia M.; Aulchenko, Yurii S.; Ripatti, Samuli (2011)
  • Äyräväinen, Leena; Heikkinen, Anna Maria; Kuuliala, Antti; Ahola, Kirsi; Koivuniemi, Riitta; Peltola, Jaakko; Suomalainen, Anni; Moilanen, Eeva; Hämäläinen, Mari; Laasonen, Leena; Meurman, Jukka H.; Leirisalo-Repo, Marjatta (2018)
    To study oral health in patients with rheumatoid arthritis (RA) with emphasis on disease activity and treatment of RA. In this prospective cohort study 81 RA patients [53 early untreated RA (EURA) and 28 chronic RA (CRA) patients with inadequate response to synthetic disease modifying antirheumatic drugs (DMARDs)], underwent rheumatological [Disease Activity Score (28-joint) DAS28] and dental examinations [Total Dental Index (TDI), Decayed Missing Filled Teeth (DMFT) and Decayed Missing Filled Surfaces (DMFS)]. For controls, 43 volunteers were examined. After the examinations, EURA patients started treatment with synthetic DMARDs, oral and intra-articular glucocorticoids. CRA patients were candidates for biological DMARDs. The patients were re-examined mean 16 months later. Results were analyzed with descriptive statistics and logistic regression. TDI was higher in both RA groups at baseline compared to controls [EURA: 2 (2-3); CRA: 2 (1-3); controls 1 (1-3), p = 0.045]. DMFT [r(s) 0.561 (p = 0.002)] and DMFS [r(s) 0.581 (p = 0.001)] associated with DAS28 at baseline in CRA patients. After follow-up, DAS28 associated positively with DMFT [r(s) 0.384 (p = 0.016)] and DMFS [r(s) 0.334 (p = 0.038)] in EURA patients; as well as in CRA patients DMFT [r (s) 0.672 (p = 0.001)], DMFS [r(s) 0.650 (p = 0.001)]. RA patients already in the early phase of the disease had poorer oral health compared to controls. The caries indices associated with the activity of RA in both patient groups. Oral status may thus contribute to the development and further relate to the activity of RA.
  • Honkamäki, Jasmin; Hisinger-Mölkänen, Hanna; Ilmarinen, Pinja; Piirilä, Päivi; Tuomisto, Leena E.; Andersen, Heidi; Huhtala, Heini; Sovijärvi, Anssi; Backman, Helena; Lundbäck, Bo; Rönmark, Eva; Lehtimäki, Lauri; Kankaanranta, Hannu (2019)
    Background: Asthma is currently divided into different phenotypes, with age at onset as a relevant differentiating factor. In addition, asthma with onset in adulthood seems to have a poorer prognosis, but studies investigating age-specific incidence of asthma with a wide age span are scarce. Objective: To evaluate incidence of asthma diagnosis at different ages and differences between child- and adult-diagnosed asthma in a large population-based study, with gender-specific analyzes included. Methods: In 2016, a respiratory questionnaire was sent to 8000 randomly selected subjects aged 20-69 years in western Finland. After two reminders, 4173 (52.3%) subjects responded. Incidence rate of asthma was retrospectively estimated based on the reported age of asthma onset. Adult-diagnosed asthma was defined as a physician-diagnosis of asthma made at >= 18 years of age. Results: Among those with physician-diagnosed asthma, altogether, 63.7% of subjects, 58.4% of men and 67.8% of women, reported adult-diagnosed asthma. Incidence of asthma diagnosis was calculated in 10-year age groups and it peaked in young boys (0-9 years) and middle-aged women (40-49 years) and the average incidence rate during the examined period between 1946 and 2015 was 2.2/1000/year. Adult-diagnosed asthma became the dominant phenotype among those with physician-diagnosed asthma by age of 50 years and 38 years in men and women, respectively. Conclusions: Asthma is mainly diagnosed during adulthood and the incidence of asthma diagnosis peaks in middle-aged women. Asthma diagnosed in adulthood should be considered more in clinical practice and management guidelines.
  • Danielsson, Maria; Lammi, Anelma; Siitonen, Simo; Ollgren, Jukka; Pylkkanen, Liisa; Vasankari, Tuula (2019)
    Background The consumption of tobacco products has evolved to include more complex combinations of different products. We investigated the tobacco habits of a representative population of young Finnish male conscripts in order to evaluate the prevalence of dual use of cigarettes and snus as well as the transition from one tobacco product to another. In addition, we evaluated the correlation between the level of education and the use of cigarettes and snus. Methods A questionnaire-based survey was carried out in three out of 17 garrisons among conscripts during their first week of service in 2014. A total of 1971 male conscripts were selected by simple random sampling of the 9013 males in the selected garrisons. Of them 1916 participated and filled in the questionnaire. The response rate was 97.2%. The questionnaire consisted of 25 questions including age, gender, basic education, use of tobacco products as well as questions assessing nicotine dependency. Results The amount of dual users of cigarettes and snus was 21%. There was a higher probability of dual use of cigarettes and snus among smokers compared to snus users (p <0.001). One third (35%) of former smokers reported daily snus use and over 40% of the former snus users smoked daily. One third (34%) of the participants reported snus usage and 14% of the study subjects used snus daily. 40% of the study population were smokers and over 25% smoked daily. Of the participants with basic educational background 57% smoked daily (p <0.001), however, no association between snus and level of education was found (p = 0.69). Conclusions This study provides better understanding of the complex tobacco habits of young adult males. The simultaneous usage of multiple tobacco products as well as the high tendency to transition from one tobacco product to another should be taken into consideration when planning cessation interventions in health care settings and tobacco control policies at societal levels.
  • Hirvonen, Tuomas; Siironen, Jari; Marjamaa, Johan; Niemelä, Mika; Koski-Palkén, Anniina (2020)
    Background Context Anterior cervical discectomy and fusion (ACDF) procedures is thought to lead to accelerated degeneration of the adjacent cervical discs and in some cases can be symptomatic (adjacent segment disease, or ASD). The occurrence of ASD is of particular interest when treating young individuals, as the cumulative disease burden may become increasingly significant during their expectedly long lifetime. However, the overall impact of a surgical intervention on the lifetime prognosis of ASD remains unclear. Purpose Our goal was to study the long-term outcomes of ACDF surgery among those members of the young adult population who have been operated on between the ages of 18 and 40. Study design Retrospective study. Patient Sample All patients between 18 and 40 years of age at the time of surgery who underwent ACDF due to degenerative cervical disorders at Helsinki University Hospital between the years of 1990 and 2005 (476 patients). Outcome Measures Cervical reoperation rate, satisfaction with the surgery, employment status, Neck Disability Index (NDI) Methods We retrospectively analyzed the medical records of all patients between 18 and 40 years of age at the time of surgery who underwent ACDF due to degenerative cervical disorders at Helsinki University Hospital between the years of 1990 and 2005. We sent questionnaires to all available patients at the end of the follow-up (median 17.5 years) to assess their current neck symptoms, general situations, and levels of satisfaction with the surgery. Furthermore, we compared the results for different types of ACDF surgeries (i.e., discectomy only versus synthetic cage or bone autograft implantation for fusion) in propensity-score-matched groups. Results Of the 476 patients who were included in the study, surgery was performed in 72% of the cases due to intervertebral disc herniation and in 28% due to spondylotic changes. The total reoperation rate during the entire follow-up (median 17.5 years) was 24%, and 19.5% if early reoperations (
  • Virtanen, Eunice; Nurmi, Tapio; Soder, Per-Osten; Airila-Mansson, Stella; Soder, Birgitta; Meurman, Jukka H. (2017)
    Background: Periodontal disease associates with systemic diseases but corresponding links regarding apical periodontitis (AP) are not so clear. Hence our aim was to study association between AP and the prevalence of systemic diseases in a study population from Sweden. Methods: The subjects were 150 patients from a randomly selected epidemiological sample of 1676 individuals. 120 accepted to participate and their basic and clinical examination data were available for these secondary analyses where dental radiographs were used to record signs for endodontic treatments and AP. Periapical Index and modified Total Dental Index scores were calculated from the x-rays to classify the severity of AP and dental infection burden, respectively. Demographic and hospital record data were collected from the Swedish National Statistics Center. T-test, chi-square and univariate analysis of covariance (ANCOVA) and regressions analyses were used for statistics. Results: Of the 120 patients 41% had AP and 61% had received endodontic treatments of which 52% were radiographically unsatisfactory. AP patients were older and half of them were smokers. AP and periodontitis often appeared in the same patient (32.5%). From all hospital diagnoses, cardiovascular diseases (CVD) were most common, showing 20.4% prevalence in AP patients. Regression analyses, controlled for age, gender, income, smoking and periodontitis, showed AP to associate with CVD with odds ratio 3.83 (95% confidence interval 1.18-12.40; p = 0.025). Conclusions: The results confirmed our hypothesis by showing that AP statistically associated with cardiovascular diseases. The finding that subjects with AP also often had periodontitis indicates an increased oral inflammatory burden.
  • But, Anna; Wang, Haining; Mannisto, Satu; Pukkala, Eero; Haukka, Jari (2014)
  • Carslake, David; Fraser, Abigail; May, Margaret T.; Palmer, Tom; Silventoinen, Karri; Tynelius, Per; Lawlor, Debbie A.; Davey Smith, George (2019)
  • Sjosten, Noora; Kivimaki, Mika; Singh-Manoux, Archana; Ferrie, Jane E.; Goldberg, Marcel; Zins, Marie; Pentti, Jaana; Westerlund, Hugo; Vahtera, Jussi (2012)
    Objectives: To examine the trajectories of physical activity from preretirement to postretirement and to further clarify whether the changes in physical activity are associated with changes in body weight. Design: Prospective. Setting: French national gas and electricity company (GAZEL cohort). Participants: From the original sample of 20 625 employees, only those retiring between 2001 and 2008 on a statutory basis were selected for the analyses (analysis 1: n = 2711, 63% men; analysis 2: n = 3812, 75% men). Persons with data on at least one preretirement and postretirement measurement of the outcome were selected. Primary and secondary outcome measures: All outcome data were gathered by questionnaires. In analysis 1, the annual prevalence of higher physical activity (walking >= 5 km/week) 4 years before and after retirement was analysed. In analysis 2, changes in leisure-time sport activities (engagement, frequency and manner) from preretirement to postretirement were analysed with simultaneous changes in body weight (kilogram). Results: In analysis 1 (n = 2711), prevalence estimates for 4 years before and 4 years after retirement showed that higher leisure-time physical activity (walking at least 5 km/week) increased by 36% in men and 61% in women during the transition to retirement. This increase was also observed among people at a higher risk of physical inactivity, such as smokers and those with elevated depressive symptoms. In a separate sample (analysis 2, n = 3812), change in weight as a function of preretirement and postretirement physical activity was analysed. Weight gain preretirement to postretirement was 0.85 (95% CI 0.48 to 1.21) to 1.35 (0.79 to 1.90) kg greater among physically inactive persons (decrease in activity or inactive) compared with those physically active (p Conclusions: Retirement transition may be associated with beneficial changes in lifestyle and may thus be a good starting point to preventive interventions in various groups of individuals in order to maintain long-term changes.
  • Herzog, Katharina; Ahlqvist, Emma; Alfredsson, Lars; Groop, Leif; Hjort, Rebecka; Löfvenborg, Josefin E.; Tuomi, Tiinamaija; Carlsson, Sofia (2021)
    Aims: We investigated the risk of latent autoimmune diabetes in adults (LADA) and type 2 diabetes in relation to a healthy lifestyle, the proportion of patients attributable to an unhealthy lifestyle, and the influence of family history of diabetes (FHD) and genetic susceptibility. Methods: The population-based study included incident LADA (n = 571), type 2 diabetes (n = 1962), and matched controls (n = 2217). A healthy lifestyle was defined by BMI < 25 kg/m2, moderate-to-high physical activity, a healthy diet, no smoking, and moderate alcohol consumption. We estimated odds ratios (OR) with 95% confidence intervals (CIs) adjusted for age, sex, education, and FHD. Results: Compared to a poor/moderate lifestyle, a healthy lifestyle was associated with a reduced risk of LADA (OR 0.51, CI 0.34-0.77) and type 2 diabetes (OR 0.09, CI 0.05-0.15). A healthy lifestyle conferred a reduced risk irrespective of FHD and high-risk HLA genotypes. Having a BMI < 25 kg/m2 conferred the largest risk reduction for both LADA (OR 0.54, CI 0.43-0.66) and type 2 diabetes (OR 0.12, CI 0.10-0.15) out of the individual items. Conclusion: People with a healthy lifestyle, especially a healthy body weight, have a reduced risk of LADA including those with genetic susceptibility to diabetes. (C) 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (
  • Mackenbach, Johan P.; Valverde, Jose Rubio; Bopp, Matthias; Bronnum-Hansen, Henrik; Deboosere, Patrick; Kalediene, Ramune; Kovacs, Katalin; Leinsalu, Mall; Martikainen, Pekka; Menvielle, Gwenn; Regidor, Enrique; Nusselder, Wilma J. (2019)
    Background Socioeconomic inequalities in longevity have been found in all European countries. We aimed to assess which determinants make the largest contribution to these inequalities. Methods We did an international comparative study of inequalities in risk factors for shorter life expectancy in Europe. We collected register-based mortality data and survey-based risk factor data from 15 European countries. We calculated partial life expectancies between the ages of 35 years and 80 years by education and gender and determined the effect on mortality of changing the prevalence of eight risk factors-father with a manual occupation, low income, few social contacts, smoking, high alcohol consumption, high bodyweight, low physical exercise, and low fruit and vegetable consumption-among people with a low level of education to that among people with a high level of education (upward levelling scenario), using population attributable fractions. Findings In all countries, a substantial gap existed in partial life expectancy between people with low and high levels of education, of 2.3-8.2 years among men and 0.6-4.5 years among women. The risk factors contributing most to the gap in life expectancy were smoking (19.8% among men and 18.9% among women), low income (9.7% and 13.4%), and high bodyweight (7.7% and 11.7%), but large differences existed between countries in the contribution of risk factors. Sensitivity analyses using the prevalence of risk factors in the most favourable country (best practice scenario) showed that the potential for reducing the gap might be considerably smaller. The results were also sensitive to varying assumptions about the mortality risks associated with each risk factor. Interpretation Smoking, low income, and high bodyweight are quantitatively important entry points for policies to reduce educational inequalities in life expectancy in most European countries, but priorities differ between countries. A substantial reduction of inequalities in life expectancy requires policy actions on a broad range of health determinants. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd.
  • Hu, Yannan; van Lenthe, Frank J.; Judge, Ken; Lahelma, Eero; Costa, Giuseppe; de Gelder, Rianne; Mackenbach, Johan P. (2016)
    Background: Between 1997 and 2010, the English government pursued an ambitious programme to reduce health inequalities, the explicit and sustained commitment of which was historically and internationally unique. Previous evaluations have produced mixed results. None of these evaluations have, however, compared the trends in health inequalities within England with those in other European countries. We carried out an innovative analysis to assess whether changes in trends in health inequalities observed in England after the implementation of its programme, have been more favourable than those in other countries without such a programme. Methods: Data were obtained from nationally representative surveys carried out in England, Finland, the Netherlands and Italy for years around 1990, 2000 and 2010. A modified difference-in-difference approach was used to assess whether trends in health inequalities in 2000-2010 were more favourable as compared to the period 1990-2000 in England, and the changes in trends in inequalities after 2000 in England were then compared to those in the three comparison countries. Health outcomes were self-assessed health, long-standing health problems, smoking status and obesity. Education was used as indicator of socioeconomic position. Results: After the implementation of the English strategy, more favourable trends in some health indicators were observed among low-educated people, but trends in health inequalities in 2000-2010 in England were not more favourable than those observed in the period 1990-2000. For most health indicators, changes in trends of health inequalities after 2000 in England were also not significantly different from those seen in the other countries. Conclusions: In this rigorous analysis comparing trends in health inequalities in England both over time and between countries, we could not detect a favourable effect of the English strategy. Our analysis illustrates the usefulness of a modified difference-in-difference approach for assessing the impact of policies on population-level health inequalities.
  • Föhr, Tiina; Waller, Katja; Viljanen, Anne; Sanchez, Riikka; Ollikainen, Miina; Rantanen, Taina; Kaprio, Jaakko; Sillanpää, Elina (2021)
    Background Epigenetic clocks are based on DNA methylation (DNAm). It has been suggested that these clocks are useable markers of biological aging and premature mortality. Because genetic factors explain variations in both epigenetic aging and mortality, this association could also be explained by shared genetic factors. We investigated the influence of genetic and lifestyle factors (smoking, alcohol consumption, physical activity, chronic diseases, body mass index) and education on the association of accelerated epigenetic aging with mortality using a longitudinal twin design. Utilizing a publicly available online tool, we calculated the epigenetic age using two epigenetic clocks, Horvath DNAmAge and DNAm GrimAge, in 413 Finnish twin sisters, aged 63-76 years, at the beginning of the 18-year mortality follow-up. Epigenetic age acceleration was calculated as the residuals from a linear regression model of epigenetic age estimated on chronological age (AA(Horvath), AA(GrimAge), respectively). Cox proportional hazard models were conducted for individuals and twin pairs. Results The results of the individual-based analyses showed an increased mortality hazard ratio (HR) of 1.31 (CI95: 1.13-1.53) per one standard deviation (SD) increase in AA(GrimAge). The results indicated no significant associations of AA(Horvath) with mortality. Pairwise mortality analyses showed an HR of 1.50 (CI95: 1.02-2.20) per 1 SD increase in AA(GrimAge). However, after adjusting for smoking, the HR attenuated substantially and was statistically non-significant (1.29; CI95: 0.84-1.99). Similarly, in multivariable adjusted models the HR (1.42-1.49) was non-significant. In AA(Horvath), the non-significant HRs were lower among monozygotic pairs in comparison to dizygotic pairs, while in AA(GrimAge) there were no systematic differences by zygosity. Further, the pairwise analysis in quartiles showed that the increased within pair difference in AA(GrimAge) was associated with a higher all-cause mortality risk. Conclusions In conclusion, the findings suggest that DNAm GrimAge is a strong predictor of mortality independent of genetic influences. Smoking, which is known to alter DNAm levels and is built into the DNAm GrimAge algorithm, attenuated the association between epigenetic aging and mortality risk.
  • Hemilä, Harri (2017)
    Background: The relative scale has been used for decades in analysing binary data in epidemiology. In contrast, there has been a long tradition of carrying out meta-analyses of continuous outcomes on the absolute, original measurement, scale. The biological rationale for using the relative scale in the analysis of binary outcomes is that it adjusts for baseline variations; however, similar baseline variations can occur in continuous outcomes and relative effect scale may therefore be often useful also for continuous outcomes. The aim of this study was to determine whether the relative scale is more consistent with empirical data on treating the common cold than the absolute scale. Methods: Individual patient data was available for 2 randomized trials on zinc lozenges for the treatment of the common cold. Mossad (Ann Intern Med 125:81-8, 1996) found 4.0 days and 43% reduction, and Petrus (Curr Ther Res 59:595-607, 1998) found 1.77 days and 25% reduction, in the duration of colds. In both trials, variance in the placebo group was significantly greater than in the zinc lozenge group. The effect estimates were applied to the common cold distributions of the placebo groups, and the resulting distributions were compared with the actual zinc lozenge group distributions. Results: When the absolute effect estimates, 4.0 and 1.77 days, were applied to the placebo group common cold distributions, negative and zero (i.e., impossible) cold durations were predicted, and the high level variance remained. In contrast, when the relative effect estimates, 43 and 25%, were applied, impossible common cold durations were not predicted in the placebo groups, and the cold distributions became similar to those of the zinc lozenge groups. Conclusions: For some continuous outcomes, such as the duration of illness and the duration of hospital stay, the relative scale leads to a more informative statistical analysis and more effective communication of the study findings. The transformation of continuous data to the relative scale is simple with a spreadsheet program, after which the relative scale data can be analysed using standard meta-analysis software. The option for the analysis of relative effects of continuous outcomes directly from the original data should be implemented in standard meta-analysis programs.
  • Savage, Jeanne E.; Rose, Richard J.; Pulkkinen, Lea; Silventoinen, Karri; Korhonen, Tellervo; Kaprio, Jaakko; Gillespie, Nathan; Dick, Danielle M. (2018)
    Early maturation, indexed by pubertal development (PD), has been associated with earlier initiation and greater frequency of adolescent substance use, but this relationship may be biased by confounding factors and effects that change across development. Using a population-based Finnish twin sample (N = 3,632 individuals), we conducted twin modeling and multilevel structural equation modeling of the relationship between PD and substance use at ages 12-22. Shared environmental factors contributed to early PD and heavier substance use for females. Biological father absence was associated with early PD for boys but not girls, and did not account for the relationship between PD and substance use. The association between early PD and heavier substance use was partially due to between-family confounds, although early PD appeared to qualitatively alter long-term trajectories for some substances (nicotine), but not others (alcohol). Mediation by peer and parental factors did not explain this relationship within families. However, higher peer substance use and lower parental monitoring were themselves associated with heavier substance use, strengthening the existing evidence for these factors as targets for prevention/intervention efforts. Early maturation was not supported as a robust determinant of alcohol use trajectories in adolescence and young adulthood, but may require longer term follow-up. Subtle effects of early PD on nicotine and illicit drug use trajectories throughout adolescence and adulthood merit further investigation.
  • Saltychev, Mikhail; Laimi, Katri; El-Metwally, Ashraf; Oksanen, Tuula; Pentti, Jaana; Virtanen, Marianna; Kouvonen, Anne; Kivimaki, Mika; Vahtera, Jussi (2012)
  • Imboden, Medea; Wielscher, Matthias; Rezwan, Faisal I.; Amaral, Andre F. S.; Schaffner, Emmanuel; Jeong, Ayoung; Beckmeyer-Borowko, Anna; Harris, Sarah E.; Starr, John M.; Deary, Ian J.; Flexeder, Claudia; Waldenberger, Melanie; Peters, Annette; Schulz, Holger; Chen, Su; Sunny, Shadia Khan; Karmaus, Wilfried J. J.; Jiang, Yu; Erhart, Gertraud; Kronenberg, Florian; Arathimos, Ryan; Sharp, Gemma C.; Henderson, Alexander John; Fu, Yu; Piirilä, Päivi; Pietiläinen, Kirsi H.; Ollikainen, Miina; Johansson, Asa; Gyllensten, Ulf; de Vries, Maaike; van der Plaat, Diana A.; de Jong, Kim; Boezen, H. Marike; Hall, Ian P.; Tobin, Martin D.; Jarvelin, Marjo-Riitta; Holloway, John W.; Jarvis, Deborah; Probst-Hensch, Nicole M. (2019)
    Previous reports link differential DNA methylation (DNAme) to environmental exposures that are associated with lung function. Direct evidence on lung function DNAme is, however, limited. We undertook an agnostic epigenome-wide association study (EWAS) on pre-bronchodilation lung function and its change in adults. In a discovery-replication EWAS design, DNAme in blood and spirometry were measured twice, 6-15 years apart, in the same participants of three adult population-based discovery cohorts (n=2043). Associated DNAme markers (p EWAS signals were enriched for smoking-related DNAme. We replicated 57 lung function DNAme markers in adult, but not childhood samples, all previously associated with smoking. Markers not previously associated with smoking failed replication. cg05575921 (AHRR (aryl hydrocarbon receptor repressor)) showed the statistically most significant association with cross-sectional lung function (FEV1/FVC: pdiscovery=3.96x10(-21) and pcombined=7.22x10(-50)). A score combining 10 DNAme markers previously reported to mediate the effect of smoking on lung function was associated with lung function (FEV1/FVC: p=2.65x10(-20)). Our results reveal that lung function-associated methylation signals in adults are predominantly smoking related, and possibly of clinical utility in identifying poor lung function and accelerated decline. Larger studies with more repeat time-points are needed to identify lung function DNAme in never-smokers and in children.
  • Hemminki, Kari; Sundquist, Kristina; Sundquist, Jan; Försti, Asta; Hemminki, Akseli; Li, Xinjun (2021)
    Simple Summary Familial cancer can be defined through the occurrence of the same cancer in two or more family members. Hereditary cancer is a narrower definition of high-risk familial aggregation through identified predisposing genes. The absence of correlation between spouses for risk of most cancers, particularly those not related to tobacco smoking or solar exposure, suggests that familial cancers are mainly due to genetic causes. The aim of the present study was to define the frequency and increased risk for familial cancer. Data on 31 of the most common cancers were obtained from the Swedish Family-Cancer Database and familial relative risks (SIRs) were estimated between persons with or without family history of the same cancer in first-degree relatives. Practically all cancers showed a familial risk, with an SIR most commonly around two, or a doubling of the risk because of family history. Background: Familial cancer can be defined through the occurrence of the same cancer in two or more family members. We describe a nationwide landscape of familial cancer, including its frequency and the risk that it conveys, by using the largest family database in the world with complete family structures and medically confirmed cancers. Patients/methods: We employed standardized incidence ratios (SIRs) to estimate familial risks for concordant cancer among first-degree relatives using the Swedish Cancer Registry from years 1958 through 2016. Results: Cancer risks in a 20-84 year old population conferred by affected parents or siblings were about two-fold compared to the risk for individuals with unaffected relatives. For small intestinal, testicular, thyroid and bone cancers and Hodgkin disease, risks were higher, five-to-eight-fold. Novel familial associations included adult bone, lip, pharyngeal, and connective tissue cancers. Familial cancers were found in 13.2% of families with cancer; for prostate cancer, the proportion was 26.4%. High-risk families accounted for 6.6% of all cancer families. Discussion/Conclusion: High-risk family history should be exceedingly considered for management, including targeted genetic testing. For the major proportion of familial clustering, where genetic testing may not be feasible, medical and behavioral intervention should be indicated for the patient and their family members, including screening recommendations and avoidance of carcinogenic exposure.
  • Li, Xinjun; Koskinen, Anni I.; Hemminki, Otto; Försti, Asta; Sundquist, Jan; Sundquist, Kristina; Hemminki, Kari (2021)
    Simple Summary Head and neck cancers are cancers that arise between the mouth and larynx. Risk factors for these include smoking, alcohol, human papilloma virus (HPV) infection and family history. Because families can be identified for the whole Swedish population, we wanted to analyzed familial risks for HNC with same and different cancers among first-degree relatives. When a parent or sibling was diagnosed with HNC, other family members had a two-fold risk of being diagnosed with HNC, but the risk was higher when specific types of HNC, such as oral or nasopharyngeal cancers, were analyzed. Husbands of wives with cervical cancer had an increased risk of oropharyngeal cancer which may be related to shared HPV infection. In the Swedish population with low smoking levels, HPV is becoming a dominant risk factor, emphasizing the need for sexual hygiene and HPV vaccination. Background: Head and neck cancers (HNCs) encompass a heterogeneous group of cancers between the mouth and larynx. Familial clustering in HNCs has been described, but how it influences individual sites and to which extent known risk factors, such as human papilloma virus (HPV) infection, may contribute is not well established. Patients/methods: We employed standardized incidence ratios (SIRs) to estimate familial risks for HNC with same (concordant) and different (discordant) cancers among first-degree relatives using data from the Swedish Cancer Registry from 1958 to 2018. Results: Incidence for male and female oropharyngeal cancer increased close to four-fold in the past 39 years. Familial HNC was found in 3.4% of the study population, with an overall familial SIR of 1.78. Patients with concordant nasopharyngeal cancer showed a high risk of 23.97, followed by hypopharyngeal cancer (5.43). The husbands of wives with cervical cancer had an increased risk of oropharyngeal cancer. Discussion/Conclusion: Nasopharyngeal cancers lacked associations with lifestyle or HPV associated cancers, suggesting a role for germline genetics, which was also true for the high-risk families of three HNC patients. In the Swedish population with low smoking levels, HPV is becoming a dominant risk factor, emphasizing the need for sexual hygiene and HPV vaccination.
  • Kiiskinen, Tuomo; Mars, Nina; Palviainen, Teemu; Koskela, Jukka; Rämö, Joel; Ripatti, Pietari; Ruotsalainen, Sanni; Project, FinnGen; GSCAN Consortium,; Palotie, Aarno; Madden, Pamela A.F.; Rose, Richard J.; Kaprio, Jaakko; Salomaa, Veikko; Mäkelä, Pia; Havulinna, Aki S.; Ripatti, Samuli (2020)
    While polygenic risk scores (PRS) have been shown to predict many diseases and risk factors, the potential of genomic prediction in harm caused by alcohol use has not yet been extensively studied. Here, we built a novel polygenic risk score of 1.1 million variants for alcohol consumption and studied its predictive capacity in 96,499 participants from the FinnGen study and 39,695 participants from prospective cohorts with detailed baseline data and up to 25 years of follow-up time. A 1 SD increase in the PRS was associated with 11.2 g (=0.93 drinks) higher weekly alcohol consumption (CI = 9.85-12.58 g, p = 2.3 x 10(-58)). The PRS was associated with alcohol-related morbidity (4785 incident events) and the risk estimate between the highest and lowest quintiles of the PRS was 1.83 (95% CI = 1.66-2.01, p = 1.6 x 10(-36)). When adjusted for self-reported alcohol consumption, education, marital status, and gamma-glutamyl transferase blood levels in 28,639 participants with comprehensive baseline data from prospective cohorts, the risk estimate between the highest and lowest quintiles of the PRS was 1.58 (CI = 1.26-1.99, p = 8.2 x 10(-5)). The PRS was also associated with all-cause mortality with a risk estimate of 1.33 between the highest and lowest quintiles (CI = 1.20-1.47, p = 4.5 x 10(-8)) in the adjusted model. In conclusion, the PRS for alcohol consumption independently associates for both alcohol-related morbidity and all-cause mortality. Together, these findings underline the importance of heritable factors in alcohol-related health burden while highlighting how measured genetic risk for an important behavioral risk factor can be used to predict related health outcomes.