Browsing by Subject "CIGARETTE-SMOKING"

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  • Taylor, Amy E.; Fluharty, Meg E.; Bjorngaard, Johan H.; Gabrielsen, Maiken Elvestad; Skorpen, Frank; Marioni, Riccardo E.; Campbell, Archie; Engmann, Jorgen; Mirza, Saira Saeed; Loukola, Anu; Laatikainen, Tiina; Partonen, Timo; Kaakinen, Marika; Ducci, Francesca; Cavadino, Alana; Husemoen, Lise Lotte N.; Ahluwalia, Tarunveer Singh; Jacobsen, Rikke Kart; Skaaby, Tea; Ebstrup, Jeanette Frost; Mortensen, Erik Lykke; Minica, Camelia C.; Vink, Jacqueline M.; Willemsen, Gonneke; Marques-Vidal, Pedro; Dale, Caroline E.; Amuzu, Antoinette; Lennon, Lucy T.; Lahti, Jari; Palotie, Aarno; Räikkönen, Katri; Wong, Andrew; Paternoster, Lavinia; Wong, Angelita Pui-Yee; Horwood, L. John; Murphy, Michael; Johnstone, Elaine C.; Kennedy, Martin A.; Pausova, Zdenka; Paus, Tomas; Ben-Shlomo, Yoav; Nohr, Ellen A.; Kuh, Diana; Kivimaki, Mika; Eriksson, Johan G.; Morris, Richard W.; Casas, Juan P.; Preisig, Martin; Boomsma, Dorret I.; Linneberg, Allan; Power, Chris; Hypponen, Elina; Veijola, Juha; Jarvelin, Marjo-Riitta; Korhonen, Tellervo; Tiemeier, Henning; Kumari, Meena; Porteous, David J.; Hayward, Caroline; Romundstad, Pal R.; Smith, George Davey; Munafo, Marcus R. (2014)
  • Kauppi, Paula; Kupiainen, Henna; Lindqvist, Ari; Haahtela, Tari; Laitinen, Tarja (2014)
  • Saleheen, Danish; Zhao, Wei; Young, Robin; Nelson, Christopher P.; Ho, WeangKee; Ferguson, Jane F.; Rasheed, Asif; Ou, Kristy; Nurnberg, Sylvia T.; Bauer, Robert C.; Goel, Anuj; Do, Ron; Stewart, Alexandre F. R.; Hartiala, Jaana; Zhang, Weihua; Thorleifsson, Gudmar; Strawbridge, Rona J.; Sinisalo, Juha; Kanoni, Stavroula; Sedaghat, Sanaz; Marouli, Eirini; Kristiansson, Kati; Zhao, Jing Hua; Scott, Robert; Gauguier, Dominique; Shah, Svati H.; Smith, Albert Vernon; van Zuydam, Natalie; Cox, Amanda J.; Willenborg, Christina; Kessler, Thorsten; Zeng, Lingyao; Province, Michael A.; Ganna, Andrea; Lind, Lars; Pedersen, Nancy L.; White, Charles C.; Joensuu, Anni; Kleber, Marcus Edi; Hall, Alistair S.; Maerz, Winfried; Salomaa, Veikko; O'Donnell, Christopher; Ingelsson, Erik; Feitosa, Mary F.; Erdmann, Jeanette; Bowden, Donald W.; Palmer, Colin N. A.; Gudnason, Vilmundur; Perola, Markus; PROMIS; Cardiogramplusc4D (2017)
    BACKGROUND: Common diseases such as coronary heart disease (CHD) are complex in etiology. The interaction of genetic susceptibility with lifestyle factors may play a prominent role. However, gene-lifestyle interactions for CHD have been difficult to identify. Here, we investigate interaction of smoking behavior, a potent lifestyle factor, with genotypes that have been shown to associate with CHD risk. METHODS: We analyzed data on 60 919 CHD cases and 80 243 controls from 29 studies for gene-smoking interactions for genetic variants at 45 loci previously reported to be associated with CHD risk. We also studied 5 loci associated with smoking behavior. Study-specific gene-smoking interaction effects were calculated and pooled using fixed-effects meta-analyses. Interaction analyses were declared to be significant at a P value of <1.0x10(-3) (Bonferroni correction for 50 tests). RESULTS: We identified novel gene-smoking interaction for a variant upstream of the ADAMTS7 gene. Every T allele of rs7178051 was associated with lower CHD risk by 12% in never-smokers (P= 1.3x10(-16)) in comparison with 5% in ever-smokers (P= 2.5x10(-4)), translating to a 60% loss of CHD protection conferred by this allelic variation in people who smoked tobacco (interaction P value= 8.7x10(-5)). The protective T allele at rs7178051 was also associated with reduced ADAMTS7 expression in human aortic endothelial cells and lymphoblastoid cell lines. Exposure of human coronary artery smooth muscle cells to cigarette smoke extract led to induction of ADAMTS7. CONCLUSIONS: Allelic variation at rs7178051 that associates with reduced ADAMTS7 expression confers stronger CHD protection in never-smokers than in ever-smokers. Increased vascular ADAMTS7 expression may contribute to the loss of CHD protection in smokers.
  • Erzurumluoglu, A. Mesut; Liu, Mengzhen; Jackson, Victoria E.; Barnes, Daniel R.; Datta, Gargi; Melbourne, Carl A.; Young, Robin; Batini, Chiara; Surendran, Praveen; Jiang, Tao; Adnan, Sheikh Daud; Afaq, Saima; Agrawal, Arpana; Altmaier, Elisabeth; Antoniou, Antonis C.; Asselbergs, Folkert W.; Baumbach, Clemens; Bierut, Laura; Bertelsen, Sarah; Boehnke, Michael; Bots, Michiel L.; Brazel, David M.; Chambers, John C.; Chang-Claude, Jenny; Chen, Chu; Corley, Janie; Chou, Yi-Ling; David, Sean P.; de Boer, Rudolf A.; de Leeuw, Christiaan A.; Dennis, Joe G.; Dominiczak, Anna F.; Dunning, Alison M.; Easton, Douglas F.; Eaton, Charles; Elliott, Paul; Evangelou, Evangelos; Faul, Jessica D.; Foroud, Tatiana; Goate, Alison; Gong, Jian; Grabe, Hans J.; Haessler, Jeff; Haiman, Christopher; Hallmans, Goran; Hammerschlag, Anke R.; Harris, Sarah E.; Hattersley, Andrew; Heath, Andrew; Hsu, Chris; Iacono, William G.; Kanoni, Stavroula; Kapoor, Manav; Kaprio, Jaakko; Kardia, Sharon L.; Karpe, Fredrik; Kontto, Jukka; Kooner, Jaspal S.; Kooperberg, Charles; Kuulasmaa, Kari; Laakso, Markku; Lai, Dongbing; Langenberg, Claudia; Le, Nhung; Lettre, Guillaume; Loukola, Anu; Luan, Jian'an; Madden, Pamela A. F.; Mangino, Massimo; Marioni, Riccardo E.; Marouli, Eirini; Marten, Jonathan; Martin, Nicholas G.; McGue, Matt; Michailidou, Kyriaki; Mihailov, Evelin; Moayyeri, Alireza; Moitry, Marie; Mueller-Nurasyid, Martina; Naheed, Aliya; Nauck, Matthias; Neville, Matthew J.; Nielsen, Sune Fallgaard; North, Kari; Perola, Markus; Pharoah, Paul D. P.; Pistis, Giorgio; Polderman, Tinca J.; Posthuma, Danielle; Poulter, Neil; Qaiser, Beenish; Rasheed, Asif; Reiner, Alex; Renstrom, Frida; Rice, John; Rohde, Rebecca; Rolandsson, Olov; Samani, Nilesh J.; Samuel, Maria; Schlessinger, David; Scholte, Steven H.; Scott, Robert A.; Sever, Peter; Shao, Yaming; Shrine, Nick; Smith, Jennifer A.; Starr, John M.; Stirrups, Kathleen; Stram, Danielle; Stringham, Heather M.; Tachmazidou, Ioanna; Tardif, Jean-Claude; Thompson, Deborah J.; Tindle, Hilary A.; Tragante, Vinicius; Trompet, Stella; Turcot, Valerie; Tyrrell, Jessica; Vaartjes, Ilonca; van der Leij, Andries R.; van der Meer, Peter; Varga, Tibor V.; Verweij, Niek; Voelzke, Henry; Wareham, Nicholas J.; Warren, Helen R.; Weir, David R.; Weiss, Stefan; Wetherill, Leah; Yaghootkar, Hanieh; Yavas, Ersin; Jiang, Yu; Chen, Fang; Zhan, Xiaowei; Zhang, Weihua; Zhao, Wei; Zhao, Wei; Zhou, Kaixin; Amouyel, Philippe; Blankenberg, Stefan; Caulfield, Mark J.; Chowdhury, Rajiv; Cucca, Francesco; Deary, Ian J.; Deloukas, Panos; Di Angelantonio, Emanuele; Ferrario, Marco; Ferrieres, Jean; Franks, Paul W.; Frayling, Tim M.; Frossard, Philippe; Hall, Ian P.; Hayward, Caroline; Jansson, Jan-Hakan; Jukema, J. Wouter; Kee, Frank; Männistö, Satu; Metspalu, Andres; Munroe, Patricia B.; Nordestgaard, Borge Gronne; Palmer, Colin N. A.; Salomaa, Veikko; Sattar, Naveed; Spector, Timothy; Strachan, David Peter; van der Harst, Pim; Zeggini, Eleftheria; Saleheen, Danish; Butterworth, Adam S.; Wain, Louise V.; Abecasis, Goncalo R.; Danesh, John; Tobin, Martin D.; Vrieze, Scott; Liu, Dajiang J.; Howson, Joanna M. M. (2020)
    Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations withP <5 x 10(-8)in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P <5 x 10(-8)) in the discovery samples. Ten novel SNVs, including rs12616219 nearTMEM182, were followed-up and five of them (rs462779 inREV3L, rs12780116 inCNNM2, rs1190736 inGPR101, rs11539157 inPJA1, and rs12616219 nearTMEM182) replicated at a Bonferroni significance threshold (P <4.5 x 10(-3)) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, inCCDC141and two low-frequency SNVs inCEP350andHDGFRP2. Functional follow-up implied that decreased expression ofREV3Lmay lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.
  • Baumert, Jens; Huang, Jie; McKnight, Barbara; Sabater-Lleal, Maria; Steri, Maristella; Chu, Audrey Y.; Trompet, Stella; Lopez, Lorna M.; Fornage, Myriam; Teumer, Alexander; Tang, Weihong; Rudnicka, Alicja R.; Maelarstig, Anders; Hottenga, Jouke-Jan; Kavousi, Maryam; Lahti, Jari; Tanaka, Toshiko; Hayward, Caroline; Huffman, Jennifer E.; Morange, Pierre-Emmanuel; Rose, Lynda M.; Basu, Saonli; Rumley, Ann; Stott, David J.; Buckley, Brendan M.; de Craen, Anton J. M.; Sanna, Serena; Masala, Marco; Biffar, Reiner; Homuth, Georg; Silveira, Angela; Sennblad, Bengt; Goel, Anuj; Watkins, Hugh; Mueller-Nurasyid, Martina; Rueckerl, Regina; Taylor, Kent; Chen, Ming-Huei; de Geus, Eco J. C.; Hofman, Albert; Witteman, Jacqueline C. M.; de Maat, Moniek P. M.; Palotie, Aarno; Davies, Gail; Siscovick, David S.; Kolcic, Ivana; Wild, Sarah H.; Song, Jaejoon; McArdle, Wendy L.; Ford, Ian; Sattar, Naveed; Schlessinger, David; Grotevendt, Anne; Franzosi, Maria Grazia; Illig, Thomas; Waldenberger, Melanie; Lumley, Thomas; Tofler, Geoffrey H.; Willemsen, Gonneke; Uitterlinden, Andre G.; Rivadeneira, Fernando; Räikkönen, Katri; Chasman, Daniel I.; Folsom, Aaron R.; Lowe, Gordon D.; Westendorp, Rudi G. J.; Slagboom, P. Eline; Cucca, Francesco; Wallaschofski, Henri; Strawbridge, Rona J.; Seedorf, Udo; Koenig, Wolfgang; Bis, Joshua C.; Mukamal, Kenneth J.; van Dongen, Jenny; Widen, Elisabeth; Franco, Oscar H.; Starr, John M.; Liu, Kiang; Ferrucci, Luigi; Polasek, Ozren; Wilson, James F.; Oudot-Mellakh, Tiphaine; Campbell, Harry; Navarro, Pau; Bandinelli, Stefania; Eriksson, Johan; Boomsma, Dorret I.; Dehghan, Abbas; Clarke, Robert; Hamsten, Anders; Boerwinkle, Eric; Jukema, J. Wouter; Naitza, Silvia; Ridker, Paul M.; Voezke, Henry; Deary, Ian J.; Reiner, Alexander P.; Tregoueet, David-Alexandre; O'Donnell, Christopher J.; Strachan, David P.; Peters, Annette; Smith, Nicholas L. (2014)
  • Siren, Maria; Viikari-Juntura, Eira; Arokoski, Jari; Solovieva, Svetlana (2020)
    Objectives To determine the associations of lifestyle factors and cumulative physical workload exposures with sickness absence (SA) due to a shoulder lesion and to calculate their population attributable fractions (PAF). Methods Our nationally representative cohort consisted of 4344 individuals aged 30-62 years who participated in the Finnish Health 2000 Survey. Education, smoking, chronic diseases and work exposures were assessed during interviews and leisure time physical activity with a questionnaire. Weight and height were measured. We followed the individuals for 15 years for the first SA due to a shoulder lesion. We used competing risk regression models. We calculated PAFs to assess the proportion of SA that was attributed to modifiable risk factors. Results In the entire study population, risk factors of SA were age, daily smoking, being exposed for more than 10 years to physically heavy work and being exposed for more than 10 years to at least two specific physical workload factors. The overall PAF for the modifiable risk factors was 49%. In men, number of specific cumulative exposures, obesity and daily smoking predicted SA with PAF values of 34%, 30% and 14%, respectively. Among women, being exposed for more than 10 years to physically heavy work, number of specific cumulative exposures and daily smoking accounted for 23%, 22% and 15% of SA, respectively. Conclusions Reducing significantly prolonged exposure to physical workload factors, avoiding regular smoking in both genders and obesity in men has a high potential to prevent SA due to a shoulder lesion.
  • Vrieling, Alina; Bueno-De-Mesquita, H. Bas; Ros, Martine M.; Kampman, Ellen; Aben, Katja K.; Buchner, Frederike L.; Jansen, Eugene H.; Roswall, Nina; Tjonneland, Anne; Boutron-Ruault, Marie-Christine; Cadeau, Claire; Chang-Claude, Jenny; Kaaks, Rudolf; Weikert, Steffen; Boeing, Heiner; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Sieri, Sabina; Palli, Domenico; Panico, Salvatore; Peeters, Petra H.; Weiderpass, Elisabete; Skeie, Guri; Jakszyn, Paula; Chirlaque, Maria-Dolores; Ardanaz, Eva; Sanchez, Maria-Jose; Ehrnstrom, Roy; Malm, Johan; Ljungberg, Borje; Khaw, Kay-Tee; Wareham, Nick J.; Brennan, Paul; Johansson, Mattias; Riboli, Elio; Kiemeney, Lambertus A. (2019)
    Published associations between dietary folate and bladder cancer risk are inconsistent. Biomarkers may provide more accurate measures of nutrient status. This nested case-control analysis within the European Prospective Investigation into Cancer and Nutrition (EPIC) investigated associations between pre-diagnostic serum folate, homocysteine, vitamins B6 and B12 and the risk of urothelial cell carcinomas of the bladder (UCC). A total of 824 patients with newly diagnosed UCC were matched with 824 cohort members. Serum folate, homocysteine, and vitamins B6 and B12 were measured. Odds ratios (OR) and 95% confidence intervals (CI) for total, aggressive, and non-aggressive UCC were estimated using conditional logistic regression with adjustment for smoking status, smoking duration and intensity, and other potential confounders. Additionally, statistical interaction with smoking status was assessed. A halving in serum folate concentrations was moderately associated with risk of UCC (OR: 1.18; 95% CI: 0.98-1.43), in particular aggressive UCC (OR: 1.34; 95% CI: 1.02-1.75; p-heterogeneity = 0.19). Compared to never smokers in the highest quartile of folate concentrations, this association seemed only apparent among current smokers in the lowest quartile of folate concentrations (OR: 6.26; 95% CI: 3.62-10.81, p-interaction = 0.07). Dietary folate was not associated with aggressive UCC (OR: 1.26; 95% CI: 0.81-1.95; p-heterogeneity = 0.14). No association was observed between serum homocysteine, vitamins B6 and B12 and risk of UCC. This study suggests that lower serum folate concentrations are associated with increased UCC risk, in particular aggressive UCC. Residual confounding by smoking cannot be ruled out and these findings require confirmation in future studies with multiple measurements.
  • Aho, Hanna; Pietila, Ilkka; Joronen, Katja (2019)
  • Ranjit, Anu; Buchwald, Jadwiga; Latvala, Antti; Heikkila, Kauko; Tuulio-Henriksson, Annamari; Rose, Richard J.; Kaprio, Jaakko; Korhonen, Tellervo (2019)
    Longitudinal, genetically informative studies of the association between cigarette smoking and depressive symptoms among adolescents are limited. We examined the longitudinal association of cigarette smoking with subsequent depressive symptoms during adolescence in a Finnish twin cohort. We used prospective data from the population-based FinnTwin12 study (maximum N = 4152 individuals, 1910 twin pairs). Current smoking status and a number of lifetime cigarettes smoked were assessed at the age of 14 and depressive symptoms at the age of 17. Negative binomial regression was conducted to model the association between smoking behavior and subsequent depressive symptoms among individuals, and within-pair analyses were conducted to control for unmeasured familial confounding. Analyses were adjusted for age, sex, school grades, drinking alcohol to intoxication, health status, family structure, parental education, and smoking, as well as for pre-existing depressiveness. The results of the individual-level analyses showed that cigarette smoking at the age of 14 predicted depressive symptoms at the age of 17. Compared to never smokers, those who had smoked over 50 cigarettes (incidence rate ratio, IRR = 1.43, 95% CI 1.28-1.60) and regular smokers (IRR = 1.46, 95% CI 1.32-1.62) had higher depression scores. The associations were attenuated when adjusted for measured covariates and further reduced in within-pair analyses. In the within-pair results, the estimates were lower within monozygotic (MZ) pairs compared to dizygotic (DZ) pairs, suggesting that shared genetic factors contribute to the associations observed in individual-based analyses. Thus, we conclude that cigarette smoking is associated with subsequent depressive symptoms during adolescence, but the association is not independent of measured confounding factors and shared genetic influences.
  • Sourander, Andre; Sucksdorff, Minna; Chudal, Roshan; Surcel, Helja-Marja; Hinkka-Yli-Salomaki, Susanna; Gyllenberg, David; Cheslack-Postava, Keely; Brown, Alan S. (2019)
    OBJECTIVES: An association between maternal smoking during pregnancy and offspring attention-deficit/hyperactivity disorder (ADHD) has been shown across several studies based on self-reports. No previous studies have investigated the association of nicotine exposure measured by cotinine levels during pregnancy and offspring ADHD. METHODS: In this population-based study, 1079 patients born between 1998 and 1999 and diagnosed with ADHD according to the International Classification of Diseases and 1079 matched controls were identified from Finnish nationwide registers. Maternal cotinine levels were measured by using quantitative immunoassays from maternal serum specimens collected during the first and second trimesters of pregnancy and archived in the national biobank. RESULTS: There was a significant association between increasing log-transformed maternal cotinine levels and offspring ADHD. The odds ratio was 1.09 (95% confidence interval [CI] 1.06-1.12) when adjusting for maternal socioeconomic status, maternal age, maternal psychopathology, paternal age, paternal psychopathology, and child's birth weight for gestational age. In the categorical analyses with cotinine levels in 3 groups, heavy nicotine exposure (cotinine level >50 ng/mL) was associated with offspring ADHD, with an odds ratio of 2.21 (95% CI 1.63-2.99) in the adjusted analyses. Analyses by deciles of cotinine levels revealed that the adjusted odds for offspring ADHD in the highest decile was 3.34 (95% CI 2.02-5.52). CONCLUSIONS: The study reveals an association with and a dose-response relationship between nicotine exposure during pregnancy and offspring ADHD. Future studies incorporating maternal smoking and environmental, genetic, and epigenetic factors are warranted.
  • Danielsson, Maria; Tanner, Tarja; Patinen, Pertti; Birkhed, Dowen; Anttonen, Vuokko; Lammi, Anelma; Siitonen, Simo; Ollgren, Jukka; Pylkkanen, Liisa; Vasankari, Tuula (2021)
    Objective The health hazards of tobacco products depend on the level of exposure, but little is known about the characteristics of snus use. The aim of this study was to investigate the duration of daily exposure to snus among occasional and daily users and its associated predictive factors among young Finnish men. Design Cross-sectional questionnaire study. Setting Three out of 16 Finnish Defence Forces units. Participants 1280 young Finnish male conscripts starting their military service in 2016 chosen by simple random sampling. Primary and secondary measures The prevalence, duration of use and the amount of daily usage of snus and cigarettes were investigated. The attitudes towards perceived harmfulness of snus and the predictive factors affecting the total time of snus consumption were examined. Results Almost a fifth (19.5%) of the conscripts reported daily snus use, and a further 16% reported occasional use. Daily snus use was associated with an earlier starting age, longer duration of use and higher daily exposure time compared with occasional use. On average, daily snus users consumed 10 portions and occasional users three portions per day (p
  • Evins, A. E.; Korhonen, T.; Kinnunen, T. H.; Kaprio, J. (2017)
    Background. The relationship between smoking and suicide remains controversial. Method. A total of 16 282 twin pairs born before 1958 in Finland and alive in 1974 were queried with detailed health and smoking questionnaires in 1975 and 1981, with response rates of 89% and 84%. Smoking status and dose, marital, employment, and socio-economic status, and indicators of psychiatric and somatic illness were assessed at both time points. Emergent psychiatric and medical illness and vital status, including suicide determined by forensic autopsy, were evaluated over 35-year follow-up through government registries. The association between smoking and suicide was determined in competing risks hazard models. In twin pairs discordant for smoking and suicide, the prospective association between smoking and suicide was determined using a matched case-control design. Results. Smokers had a higher cumulative suicide incidence than former or never smokers. Heavy smokers had significantly higher suicide risk [hazard ratio (HR) 3.47, 95% confidence interval (CI) 2.31-5.22] than light smokers (HR 2.30, 95% CI 1.61-3.23) (p = 0.017). Compared with never smokers, smokers, but not former smokers, had increased suicide risk (HR 2.56, 95% CI 1.43-4.59), adjusting for depressive symptoms, alcohol and sedative-hypnotic use, and excluding those who developed serious somatic or psychiatric illness. In twin pairs discordant for smoking and suicide, suicide was more likely in smokers [odds ratio (OR) 6.0, 95% CI 2.06-23.8]. Conclusions. Adults who smoked tobacco were more likely to die by suicide, with a large, dose-dependent effect. This effect remained after consideration of many known predictors of suicide and shared familial effects, consistent with the hypothesis that exposure to tobacco smoke increases the risk of suicide.
  • Raglan, Olivia; Kalliala, Ilkka .; Markozannes, Georgios; Cividini, Sofia; Gunter, Marc J.; Nautiyal, Jaya; Gabra, Hani; Paraskevaidis, Evangelos; Martin-Hirsch, Pierre; Tsilidis, Kostas K.; Kyrgiou, Maria (2019)
    Although many risk factors could have causal association with endometrial cancer, they are also prone to residual confounding or other biases which could lead to over- or underestimation. This umbrella review evaluates the strength and validity of evidence pertaining risk factors for endometrial cancer. Systematic reviews or meta-analyses of observational studies evaluating the association between non-genetic risk factors and risk of developing or dying from endometrial cancer were identified from inception to April 2018 using PubMed, the Cochrane database and manual reference screening. Evidence was graded strong, highly suggestive, suggestive or weak based on statistical significance of random-effects summary estimate, largest study included, number of cases, between-study heterogeneity, 95% prediction intervals, small study effects, excess significance bias and sensitivity analysis with credibility ceilings. We identified 171 meta-analyses investigating associations between 53 risk factors and endometrial cancer incidence and mortality. Risk factors were categorised: anthropometric indices, dietary intake, physical activity, medical conditions, hormonal therapy use, biochemical markers, gynaecological history and smoking. Of 127 meta-analyses including cohort studies, three associations were graded with strong evidence. Body mass index and waist-to-hip ratio were associated with increased cancer risk in premenopausal women (RR per 5 kg/m(2) 1.49; CI 1.39-1.61) and for total endometrial cancer (RR per 0.1unit 1.21; CI 1.13-1.29), respectively. Parity reduced risk of disease (RR 0.66, CI 0.60-0.74). Of many proposed risk factors, only three had strong association without hints of bias. Identification of genuine risk factors associated with endometrial cancer may assist in developing targeted prevention strategies for women at high risk.
  • Fisher, Miranda L.; Loukola, Anu; Kaprio, Jaakko; Turner, Jill R. (ACADEMIC PRESS INC ELSEVIER SCIENCE, 2015)
    International Review of Neurobiology
    Smoking is currently the leading cause of preventable death in the United States and is responsible for over four million deaths annually worldwide. Therefore, there is a vast clinical unmet need with regards to therapeutics targeting smoking cessation. This is even more apparent when examining smokers co-morbid with psychiatric illness, as rates of smoking in this population are similar to 4 x higher than in the general population. Examining common genetic and molecular signaling pathways impinging upon both smoking behavior and psychiatric illness will lead to a better understanding of co-morbid disorders and potential development of novel therapeutics. Studies have implicated the Neuregulin Signaling Pathway in the pathophysiology of a number of psychiatric illnesses. Additionally, recent studies have also shown an association between the Neuregulin Signaling Pathway and smoking behaviors. This review outlines basic mechanisms of the Neuregulin Signaling Pathway and how it may be exploited for precision medicine approaches in treating nicotine dependence and mental illness.
  • Kelemen, Linda E.; Earp, Madalene; Fridley, Brooke L.; Chenevix-Trench, Georgia; Fasching, Peter A.; Beckmann, Matthias W.; Ekici, Arif B.; Hein, Alexander; Lambrechts, Diether; Lambrechts, Sandrina; Van Nieuwenhuysen, Els; Vergote, Ignace; Rossing, Mary Anne; Doherty, Jennifer A.; Chang-Claude, Jenny; Behrens, Sabine; Moysich, Kirsten B.; Cannioto, Rikki; Lele, Shashikant; Odunsi, Kunle; Goodman, Marc T.; Shvetsov, Yurii B.; Thompson, Pamela J.; Wilkens, Lynne R.; Doerk, Thilo; Antonenkova, Natalia; Bogdanova, Natalia; Hillemanns, Peter; Runnebaum, Ingo B.; du Bois, Andreas; Harter, Philipp; Heitz, Florian; Schwaab, Ira; Butzow, Ralf; Pelttari, Liisa M.; Nevanlinna, Heli; Modugno, Francesmary; Edwards, Robert P.; Kelley, Joseph L.; Ness, Roberta B.; Karlan, Beth Y.; Lester, Jenny; Orsulic, Sandra; Walsh, Christine; Kjaer, Susanne K.; Jensen, Allan; Cunningham, Julie M.; Vierkant, Robert A.; Giles, Graham G.; Bruinsma, Fiona (2018)
    Thymidylate synthase (TYMS) is a crucial enzyme for DNA synthesis. TYMS expression is regulated by its antisense mRNA, ENOSF1. Disrupted regulation may promote uncontrolled DNA synthesis and tumor growth. We sought to replicate our previously reported association between rs495139 in the TYMS-ENOSF1 3' gene region and increased risk of mucinous ovarian carcinoma (MOC) in an independent sample. Genotypes from 24,351 controls to 15,000 women with invasive OC, including 665 MOC, were available. We estimated per-allele odds ratios (OR) and 95% confidence intervals (CI) using unconditional logistic regression, and meta-analysis when combining these data with our previous report. The association between rs495139 and MOC was not significant in the independent sample (OR = 1.09; 95% CI = 0.97-1.22; p = 0.15; N = 665 cases). Meta-analysis suggested a weak association (OR = 1.13; 95% CI = 1.03-1.24; p = 0.01; N = 1019 cases). No significant association with risk of other OC histologic types was observed (p = 0.05 for tumor heterogeneity). In expression quantitative trait locus (eQTL) analysis, the rs495139 allele was positively associated with ENOSF1 mRNA expression in normal tissues of the gastrointestinal system, particularly esophageal mucosa (r = 0.51, p = 1.7 x 10(-28)), and nonsignificantly in five MOC tumors. The association results, along with inconclusive tumor eQTL findings, suggest that a true effect of rs495139 might be small.
  • Feodoroff, Maija; Harjutsalo, Valma; Forsblom, Carol; Thorn, Lena; Waden, Johan; Tolonen, Nina; Lithovius, Raija; Groop, Per-Henrik (2016)
    To evaluate the effect of cumulative smoking on the development of diabetic nephropathy. Study included 3613 patients with type 1 diabetes, participating in the Finnish Diabetic Nephropathy Study. The 12-year cumulative risk of microalbuminuria, macroalbuminuria and end-stage renal disease (ESRD) was estimated for current, ex- and nonsmokers. Cox regression analyses, with multivariable adjustments for other risk factors for diabetic nephropathy, were used to evaluate the risk at different stages of diabetic nephropathy based on the cumulative amount of smoking in pack-years. The 12-year cumulative risk of microalbuminuria was 18.9 % (95 % CI 14.6-23.0, P <0.0001) for current smokers and 15.1 % (10.3-19.6, P = 0.087) for ex-smokers, compared with 10.0 % (7.8-12.1) for nonsmokers. The corresponding risks of macroalbuminuria were 14.4 % (95 % CI 10.8-17.9, P <0.0001), 6.1 % (3.5-8.6, P = 0.082) and 4.7 % (3.0-6.4), respectively. The 12-year cumulative risk of ESRD was 10.3 % (95 % CI 8.4-12.4, P <0.0001) for current smokers and 10.0 % (7.9-12.3, P <0.0001) for ex-smokers, compared with 5.6 % (4.6-6.7) for nonsmokers. In the current smokers, one pack-year increased the risk of macroalbuminuria with a HR of 1.025 (1.010-1.041) and the risk of ESRD with a HR of 1.014 (1.001-1.026) compared with nonsmokers, in the fully adjusted model. In the ex-smokers, the risk of macroalbuminuria and ESRD was no different from the risk in nonsmokers after multivariable adjustment. Current smoking is a risk factor for the progression of diabetic nephropathy and the risk increases with the increasing dose of smoking. Ex-smokers seem to carry a similar risk of progression of diabetic nephropathy as nonsmokers.
  • Chatzidionysiou, K.; Lukina, G.; Gabay, C.; Hetland, M. L.; Hauge, E. M.; Pavelka, K.; Nordström, D.; Canhao, H.; Tomsic, M.; Rotar, Z.; Lie, E.; Kvien, T. K.; van Vollenhoven, R. F.; Saevarsdottir, S. (2019)
    Objectives: To investigate whether smoking habits predict response to rituximab (RTX) in rheumatoid arthritis (RA). Method: We included patients from the CERERRA international cohort receiving the first treatment cycle with available smoking status (n = 2481, smokers n = 528, non-current smokers n = 1953) and at least one follow-up visit. Outcome measures were change in Disease Activity Score based on 28-joint count (Delta DAS28) and European League Against Rheumatism (EULAR) good response at 6 months, with non-current smokers as the referent group. Results: Compared with non-smokers at baseline, smokers were more often rheumatoid factor (RF)/anti-citrullinated protein antibody (ACPA) positive and males, had shorter disease duration, lower DAS28 and Health Assessment Questionnaire (HAQ) score, a higher number of prior biological disease-modifying anti-rheumatic drugs, and were more likely to receive concomitant conventional synthetic disease-modifying anti-rheumatic drug (csDMARDs). Disease activity had decreased less in smokers at 6 months (Delta DAS28 = 1.5 vs 1.7, p = 0.006), although the difference was no longer significant after correction for baseline DAS28 (p = 0.41). EULAR good response rates did not differ between smokers and non-smokers overall or stratified by RF/ACPA status, although smokers had lower good response rates among seronegative patients (ACPA-negative: 6% vs 14%, RF-negative: 11% vs 18%). Smoking did not predict good response [odds ratio (OR) = 1.04, 95% confidence interval (CI) = 0.76-1.41], while ACPA, DAS28, HAQ, and concomitant csDMARDs were significant predictors for good response. However, when stratified by country, smokers were less likely to achieve good response in Sweden (unadjusted OR = 0.24, 95% CI = 0.07-0.89), and a trend was seen in the Czech Republic (OR = 0.45, 95% CI = 0.16-1.02). Conclusion: In this large, observational, multinational RA cohort, smokers starting RTX differed from non-smokers by having shorter disease duration and lower disease activity, but more previous treatments. The overall results do not support smoking as an important predictor for response to RTX in patients with RA.
  • Tsai, Pei-Chien; Glastonbury, Craig A.; Eliot, Melissa N.; Bollepalli, Sailalitha; Yet, Idil; Castillo-Fernandez, Juan E.; Carnero-Montoro, Elena; Hardiman, Thomas; Martin, Tiphaine C.; Vickers, Alice; Mangino, Massimo; Ward, Kirsten; Pietilaeinen, Kirsi H.; Deloukas, Panos; Spector, Tim D.; Vinuela, Ana; Loucks, Eric B.; Ollikainen, Miina; Kelsey, Karl T.; Small, Kerrin S.; Bell, Jordana T. (2018)
    Background: Tobacco smoking is a risk factor for multiple diseases, including cardiovascular disease and diabetes. Many smoking-associated signals have been detected in the blood methylome, but the extent to which these changes are widespread to metabolically relevant tissues, and impact gene expression or metabolic health, remains unclear. Methods: We investigated smoking-associated DNA methylation and gene expression variation in adipose tissue biopsies from 542 healthy female twins. Replication, tissue specificity, and longitudinal stability of the smoking-associated effects were explored in additional adipose, blood, skin, and lung samples. We characterized the impact of adipose tissue smoking methylation and expression signals on metabolic disease risk phenotypes, including visceral fat. Results: We identified 42 smoking-methylation and 42 smoking-expression signals, where five genes (AHRR, CYP1A1, CYP1B1, CYTL1, F2RL3) were both hypo-methylated and upregulated in current smokers. CYP1A1 gene expression achieved 95% prediction performance of current smoking status. We validated and replicated a proportion of the signals in additional primary tissue samples, identifying tissue-shared effects. Smoking leaves systemic imprints on DNA methylation after smoking cessation, with stronger but shorter-lived effects on gene expression. Metabolic disease risk traits such as visceral fat and android-to-gynoid ratio showed association with methylation at smoking markers with functional impacts on expression, such as CYP1A1, and at tissue-shared smoking signals, such as NOTCH1. At smoking-signals, BHLHE40 and AHRR DNA methylation and gene expression levels in current smokers were predictive of future gain in visceral fat upon smoking cessation. Conclusions: Our results provide the first comprehensive characterization of coordinated DNA methylation arid gene expression markers of smoking in adipose tissue. The findings relate to human metabolic health and give insights into understanding the widespread health consequence of smoking outside of the lung.
  • Hulkkonen, Sina; Auvinen, Juha; Miettunen, Jouko; Karppinen, Jaro; Ryhänen, Jorma (2019)
    Ulnar nerve entrapment is the second most common compression neuropathy of the upper extremity. It has been associated with smoking in cross-sectional studies. Our aim was to study whether smoking is associated with ulnar nerve entrapment. The study population consisted of the Northern Finland Birth Cohort 1966 participants, who attended the 31-year follow-up in 1997 (N = 8,716). Information on smoking, body mass index (BMI), long-term illnesses, and socio-economic status were recorded at baseline in 1997. Data on hospitalizations due to ulnar nerve entrapment neuropathies was obtained from the Care Register for Health Care, 1997-2016. Hazard ratios (HR) with 95% confidence intervals (CI) and population attributable risk (PAR) were calculated adjusted for gender, BMI and socio-economic status. 66 patients were diagnosed with ulnar nerve entrapment in the follow-up 1997-2016. Before the age of 31 years, smoking 10 pack years with more than five-folded (HR = 5.61, 95% CI = 2.80-11.23) risk for ulnar nerve entrapment compared to non-smokers in the adjusted analyses. Adjusted PAR for smoking (reference of no smoking) was 53.6%. In our study, smoking associated with increased risk for ulnar nerve entrapment, accounting for considerable proportion of increased risk.
  • Hisinger-Mölkänen, Hanna; Piirilä, Päivi; Haahtela, Tari; Sovijärvi, Anssi; Pallasaho, Paula (2018)
    Background: Allergic and non-allergic rhinitis cause a lot of symptoms in everyday life. To decrease the burden more information of the preventable risk factors is needed. We assessed prevalence and risk factors for chronic nasal symptoms, exploring the effects of smoking, environmental tobacco smoke, exposure to occupational irritants, and their combinations. Methods: In 2016, a postal survey was conducted among a random population sample of 8000 adults in Helsinki, Finland with a 50.5% response rate. Results: Smoking was associated with a significant increase in occurrence of chronic rhinitis (longstanding nasal congestion or runny nose), but not with self-reported or physician diagnosed allergic rhinitis. The highest prevalence estimates of nasal symptoms, 55.1% for chronic rhinitis, 49.1% for nasal congestion, and 40.7% for runny nose, were found among smokers with occupational exposure to gases, fumes or dusts. Besides active smoking, also exposure to environmental tobacco smoke combined with occupational exposure increased the risk of nasal symptoms. Conclusions: Smoking, environmental tobacco smoke, and occupational irritants are significant risk factors for nasal symptoms with an additive pattern. The findings suggest that these factors should be systematically inquired in patients with nasal symptoms for appropriate preventive measures. (192 words).