Ulla Broms

Smoking cessation by socioeconomic status and marital status: The contribution of smoking behavior and family background

We studied socioeconomic status and marital status as predictors of smoking cessation, adjusting for previous smoking behavior and family background by using a large Finnish prospective twin dataset unselected for smoking behavior. The data were collected by postal surveys in 1981 and 1990, and the sample comprised 3,069 current smokers, of whom 20% had quit smoking by 1990. Logistic regression analyses of all twin individuals and conditional logistic regression analysis of discordant pairs were used to predict smoking cessation. High education predicted smoking cessation among both men (OR=2.32, 95% CI=1.31-4.10) and women (OR=3.98, 95% CI=1.85-8.51) as did high social class among women. Additionally, starting at a late age, smoking a small number of cigarettes per day, and a low level of nicotine per cigarette predicted cessation. Socioeconomic differences in cessation diminished only slightly when we adjusted for smoking behavior factors. Among the twin pairs who were discordant in terms of smoking cessation, the twin who continued smoking also smoked more on average at baseline (men: OR=.94, 95% CI=.89-.99; women: OR=.82, 95% CI=.71-.94). The male twins who continued smoking had a smaller probability of getting married during the follow-up than had the cotwin who had quit smoking (OR=3.91, 95% CI=1.02-15.02). Indicators of socioeconomic status were important predictors of smoking cessation even when we adjusted for previous smoking behavior. For men, marriage was associated with an increased probability of cessation

Association of serum cotinine level with a cluster of three nicotinic acetylcholine receptor genes (CHRNA3/CHRNA5/CHRNB4) on chromosome 15

A cluster of three nicotinic acetylcholine receptor genes on chromosome 15 (CHRNA5/CHRNA3/CHRNB4) has been shown to be associated with nicotine dependence and smoking quantity. The aim of this study was to clarify whether the variation at this locus regulates nicotine intake among smokers by using the level of a metabolite of nicotine, cotinine, as an outcome. The number of cigarettes smoked per day (CPD) and immune-reactive serum cotinine level were determined in 516 daily smokers (age 30-75 years, 303 males) from the population-based Health2000 study. Association of 21 SNPs from a 100 kb region of chromosome 15 with cotinine and CPD was examined. SNP rs1051730 showed the strongest association to both measures. However, this SNP accounted for nearly a five-fold larger proportion of variance in cotinine levels than in CPD (R(2) 4.3% versus 0.9%). The effect size of the SNP was 0.30 for cotinine level, whereas it was 0.13 for CPD. Variation at CHRNA5/CHRNA3/CHRNB4 cluster influences nicotine level, measured as cotinine, more strongly than smoking quantity, measured by CPD, and appears thus to be involved in regulation of nicotine levels among smokers.

Smoking behaviour as a predictor of depression among Finnish men and women: a prospective cohort study of adult twins

BACKGROUND Depression is associated with smoking, but the causality of the relationship is debated. The authors examine smoking behaviour as a predictor of depression among the Finnish adult twin population. METHOD Based on responses to surveys in 1975 and 1981, the authors characterized the subjects as never smokers, persistent former smokers, quitters, recurrent smokers and persistent smokers. The Beck Depression Inventory (BDI) was applied in 1990 to measure depression (BDI score >9). Although the population consisted of twins, the authors first considered the subjects as individuals. Logistic regression models were computed for 4164 men and 4934 women. In order to control for family and genetic background, conditional logistic regression analyses were conducted among twin pairs discordant for depression. Bivariate genetic modelling was used to examine genetic and environmental components of the correlation between smoking and depression. RESULTS Among the men, persistent smoking (OR 1 x 42, 95% CI 1 x 07-1 x 89) and smoking in 1975 but quitting by 1981 (OR 1 x 68, 95% CI 1 x 17-2 x 42) was associated with a higher risk of depression, while among the women only the quitters had an elevated risk (OR 1 x 38, 96% CI 1 x 01-1 x 87). The gender x smoking interaction showed persistent smoking to be a stronger risk for men. When family and genetic background were controlled, smoking remained a predictor of depression. Genetic modelling among the men suggested a modest correlation (rg=0 x 25) between genetic components of smoking and depression. CONCLUSIONS Smoking behaviour may be a gender-sensitive predictor of depression, the stronger association in men being partly accounted for by having underlying genes in common.

Genetic Linkage to Chromosome 22q12 for a Heavy-Smoking Quantitative Trait in Two Independent Samples

We conducted a genomewide linkage screen of a simple heavy-smoking quantitative trait, the maximum number of cigarettes smoked in a 24-h period, using two independent samples: 289 Australian and 155 Finnish nuclear multiplex families, all of which were of European ancestry and were targeted for DNA analysis by use of probands with a heavy-smoking phenotype. We analyzed the trait, using a regression of identity-by-descent allele sharing on the sum and difference of the trait values for relative pairs. Suggestive linkage was detected on chromosome 22 at 27-29 cM in each sample, with a LOD score of 5.98 at 26.96 cM in the combined sample. After additional markers were used to localize the signal, the LOD score was 5.21 at 25.46 cM. To assess the statistical significance of the LOD score in the combined sample, 1,000 simulated genomewide screens were conducted, resulting in an empirical P value of .006 for the LOD score of 5.21. This linkage signal is driven mainly by the microsatellite marker D22S315 (22.59 cM), which had a single-point LOD score of 5.41 in the combined sample and an empirical P value <.001 from 1,000 simulated genomewide screens. This marker is located within an intron of the gene ADRBK2, encoding the beta-adrenergic receptor kinase 2. Fine mapping of this linkage region may reveal variants contributing to heaviness of smoking, which will lead to a better understanding of the genetic mechanisms underlying nicotine dependence.

Tendency Toward Eveningness Is Associated With Unhealthy Dietary Habits

Subjects with higher preference for evening hours in daily activities (eveningness) have been repeatedly shown to practice adverse health behaviors as compared to those preferring morning hours (morningness). However, associations between chronotype and dietary intake have not been explored intensively. The authors explored whether the human chronotype is associated with food and nutrient intakes in a random sample of the population aged 25 to 74 yrs. The cross-sectional study included 4493 subjects from the National FINRISK 2007 Study. Chronotype was assessed using a shortened version of Horne and Östbergs Morningness-Eveningness Questionnaire. Diet was assessed using a validated food frequency questionnaire. Associations between morningness-eveningness (ME) score and dietary intakes were analyzed by linear regression and difference between lowest (eveningness) and highest (morningness) ME score quintiles by Tukeys test. In the multivariable model, intakes of whole grain, rye, potatoes, and vegetables and roots decreased, whereas those of wine and chocolate increased with lower ME scores. Participants in the lowest ME score quintile consumed less fish (p < .001) and fruits (p = .025) and more chocolate (p = .001) and soft drinks (p = .015) compared to the highest quintile. No linear association was found between ME score and total energy intake. In regression analyses, intake of alcohol (as a percentage of total energy intake; E%) and sucrose (E%) increased, whereas intake of carbohydrates (E%), protein (E%), fiber, folic acid, and sodium decreased with lower ME scores. Furthermore, participants in the lowest ME score quintile ingested more fat (E%) (p < .001) and less vitamin D (p < .001) compared to the highest quintile, even though no linear trend between ME score and these nutrients emerged. In conclusion, these results support existing evidence that individuals with circadian preference toward eveningness have less healthy lifestyles, such as unfavorable dietary habits, than those with tendency toward morningness, which could put them at higher risk of several chronic diseases. (Author correspondence: noora.kanerva@thl.fi)

Genetics of Smoking Behavior

The public health significance of sustained smoking is difficult to overstate. Worldwide, every other current smoker will prematurely die from tobacco-related diseases (Doll, Peto, Wheatley, Gray, & Sutherland, 1994; Neubauer et al., 2006). Should current trends continue, annual deaths attributable to smoking will exceed 10 million by 2025 (Mackay, Eriksen, & Shafey, 2006). Persistent smoking is the most preventable cause of disability and death; it is associated with wide-ranging adverse health effects, including heart disease, pulmonary disease, and lung and other cancers (Doll, Peto, Boreham, & Sutherland, 2005; Risch et al., 1993) in both industrialized and developing countries (Mackay, et al.). Smoking behaviors aggregate in families and in peer networks, due to genetic dispositions and familial and extrafamilial environmental influences. In a recent study of adult twins, achieving a high school education halved the likelihood of persistent smoking, parental smoking almost doubled it and having an MZ co-twin who ever smoked increased the likelihood nearly 10-fold (Hamilton et al., 2006). Smoking, like drinking, may be understood within a developmental framework – behavior for which precursors are found in early childhood with causal modifiers evident throughout lifetime. Risk of nicotine dependence is conditional on initiating smoking; some at high risk never smoke, and the factors underlying individual differences in smoking initiation, like those underlying drinking/abstaining, are multiple in nature and include factors outside, as well as within, family households. A developmental perspective is necessary to appreciate the associations of smoking behaviors with drinking, with other patterns of substance use/abuse, and with behav-

Analysis of Detailed Phenotype Profiles Reveals CHRNA5-CHRNA3-CHRNB4 Gene Cluster Association With Several Nicotine Dependence Traits

INTRODUCTION The role of the nicotinic acetylcholine receptor gene cluster on chromosome 15q24-25 in the etiology of nicotine dependence (ND) is still being defined. In this study, we included all 15 tagging single nucleotide polymorphisms (SNPs) within the CHRNA5-CHRNA3-CHRNB4 cluster and tested associations with 30 smoking-related phenotypes. METHODS The study sample was ascertained from the Finnish Twin Cohort study. Twin pairs born 1938-1957 and concordant for a history of cigarette smoking were recruited along with their family members (mainly siblings), as part of the Nicotine Addiction Genetics consortium. The study sample consisted of 1,428 individuals (59% males) from 735 families, with mean age 55.6 years. RESULTS We detected multiple novel associations for ND. DSM-IV ND symptoms associated significantly with the proxy SNP Locus 1 (rs2036527, p = .000009) and Locus 2 (rs578776, p = .0001) and tolerance factor of the Nicotine Dependence Syndrome Scale (NDSS) showed suggestive association to rs11636753 (p = .0059), rs11634351 (p = .0069), and rs1948 (p = .0071) in CHRNB4. Furthermore, we report significant association with DSM-IV ND diagnosis (rs2036527, p = .0003) for the first time in a Caucasian population. Several SNPs indicated suggestive association for traits related to ages at smoking initiation. Also, rs11636753 in CHRNB4 showed suggestive association with regular drinking (p = .0029) and the comorbidity of depression and ND (p = .0034). CONCLUSIONS We demonstrate novel associations of DSM-IV ND symptoms and the NDSS tolerance subscale. Our results confirm and extend association findings for other ND measures. We show pleiotropic effects of this gene cluster on multiple measures of ND and also regular drinking and the comorbidity of ND and depression.

Linkage of nicotine dependence and smoking behavior on 10q, 7q and 11p in twins with homogeneous genetic background

The significant worldwide health burden introduced by tobacco smoking highlights the importance of studying the genetic determinants of smoking behavior and the key factor sustaining compulsive smoking, that is, nicotine dependence (ND). We have here addressed the genetic background of smoking in a special study sample of twins, harmonized for early life events and specifically ascertained for smoking from the nationwide twin cohort of the genetically unique population of Finland. The twins and their families were carefully examined for extensive phenotype profiles and a genome-wide scan was performed to identify loci behind the smoking status, ND and the comorbid phenotype of ND and alcohol use in 505 individuals from 153 families. We replicated previous linkage findings on 10q (max logarithm of the odds (LOD) 3.12) for a smoker phenotype, and on 7q and 11p (max LOD 2.50, and 2.25, respectively) for the ND phenotype. The loci linked for ND also showed evidence for linkage for the comorbid phenotype. Our study provides confirmatory evidence for the involvement of these genome regions in the genetic etiology of smoking behavior and ND and for the first time associates drinking and smoking to a shared locus on 10q.

Smoking affects diagnostic salivary periodontal disease biomarker levels in adolescents.

BACKGROUND The effects of smoking on periodontal biomarkers in adolescents are unknown. This study investigates matrix metalloproteinase (MMP)-8 and polymorphonuclear leukocyte elastase levels in saliva together with periodontal health indices accounting for body mass index and smoking in a birth cohort from Finland. METHODS The oral health of boys (n = 258) and girls (n = 243) aged 15 to 16 years was examined clinically. Health habits were assessed by questionnaire. Saliva samples were collected and analyzed by immunofluorometric and peptide assays for MMP-8 levels and polymorphonuclear leukocyte elastase activities, and investigated statistically with the background factors. RESULTS Median MMP-8 values of male smokers were 112.03 microg/l compared to 176.89 microg/l of non-smokers (P = 0.05). For female smokers corresponding values were 170.88 microg/l versus 177.92 microg/l in non-smokers (not statistically significant). Elastase values in male smokers were 5.88 x 10(-3) Delta OD(405)/h versus 11.0 x 10(-3) Delta OD(405)/h in non-smokers (P = 0.02), and in female smokers 9.16 x 10(-3) Delta OD(405)/h versus 10.88 x 10(-3) Delta OD(405)/h in non-smokers (P = 0.72). The effect was strengthened by high pack-years of smoking (MMP-8, P = 0.04; elastase, P = 0.01). Both biomarkers increased with gingival bleeding. However, statistically significant associations were observed with bleeding on probing and MMP-8 (P = 0.04); MMP-8 was suggestively associated with probing depth (P = 0.09) in non-smoking boys. In smokers with calculus, MMP-8 increased after adjusting with body mass index (P = 0.03). No corresponding differences were seen in girls. CONCLUSIONS Smoking significantly decreased both biomarkers studied. Compared to girls, boys seem to have enhanced susceptibility for periodontitis as reflected in salivary MMP-8 values.

Evening types are more often current smokers and nicotine-dependent-a study of Finnish adult twins.

AIMS To examine the association between diurnal type and smoking status and nicotine dependence (ND). DESIGN A cohort study using random-effects model regressions for repeated longitudinal panel data was used to analyse smoking status by diurnal type. Regression analyses examined the association between diurnal type and ND. PARTICIPANTS A total of 23, 289 same-sex adult twin individuals from Finnish Twin Cohort. Nicotine dependence was studied in a subsample of 676 twin individuals. MEASUREMENTS Subjects were classified by self-report into four categories: morning type, somewhat morning type, somewhat evening type, evening type (in 1981). Smoking status was defined as current and ever smoking (in 1975, 1981 and 1990). ND was measured by DSM-IV and Fagerström Test for Nicotine Dependence (FTND) (during 2001-05). Findings  Evening types of both genders were much more likely to be current (OR = 2.91, 95% CI 2.50, 3.38) and life-time smokers (OR = 2.67, 95% CI 2.96, 4.07) compared to morning types. Evening types were less likely to stop smoking. The risk of nicotine dependence assessed by DSM-IV criteria was higher among evening types (OR = 2.78, 95% CI 1.64, 4.72). Evening types scored 0.59 (95% CI 0.01, 1.17) points higher than morning types on the FTND. Adjustment for potential confounders did not change these associations. CONCLUSIONS Being an evening type is associated independently with a higher risk of being a current smoker, being more highly dependent upon cigarettes and a lower likelihood of stopping smoking. Understanding the cause of these associations could elucidate the causes of tobacco addiction.