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Smoking and Cannabis Use among Childhood Cancer Survivors: Results of the French Childhood Cancer Survivor Study

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Abstract

Background: Unhealthy behaviors among childhood cancer survivors increase the risks for cancer treatment adverse effects. We aimed to assess tobacco and cannabis use prevalence in this population and to identify factors associated with these consumptions. Methods: This study involved 2,887 5-year survivors from the French childhood cancer survivor study (FCCSS) cohort. Data on health behaviors were compared with those of controls from the general population. Associations of current smoking and cannabis use with clinical features, sociodemographic characteristics and health-related quality of life (QOL) were investigated using multivariable logistic regressions. Results: Prevalence for tobacco use was lower in survivors (26%) than in controls (41%, P < 0.001). Among current smokers, survivors smoked more cigarettes per day and started at a younger age than controls. Women, college graduates, older, married and CNS tumour survivors, as well as those who received chemotherapy and thoracic radiation therapy, were less likely to be smokers and/or cannabis consumers than others. Participants with a poor mental QOL were more likely to smoke. Conclusions: Preventive interventions and cessation programs must be carried out as early as possible in survivors' life, especially among young males with low educational level and poor mental health. Impact: This study brings new insights to health behaviors among childhood cancer survivors from a population with high rates of smoking and cannabis use.
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Smoking and cannabis use among childhood cancer survivors:
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results of the French Childhood Cancer Survivor Study
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Nicolas Bougas1,2, Brice Fresneau3,4,5, Sandrine Pinto4, Aurélie Mayet6,7, Joffrey Marchi6, François Pein8, Imene
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Mansouri2,4,5, Neige M.Y. Journy2,4,5, Angela Jackson2,4,5, Vincent Souchard2,4,5, Charlotte Demoor-
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Goldschmidt2,4,5,9, Giao Vu-Bezin2,4,5, Carole Rubino2,4,5, Odile Oberlin3, Nadia Haddy2,4,5, Florent de
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Vathaire2,4,5, Rodrigue S. Allodji2,4,5, Agnès Dumas1
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1 Université de Paris, ECEVE UMR 1123, INSERM (National Institute for Health and Medical Research), F-
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75010 Paris, France
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2 Gustave Roussy, Department of Clinical Research, Villejuif, F-94805, France
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3 Gustave Roussy, Department of Pediatric oncology, Villejuif, F-94805, France
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4 Université Paris-Saclay, Université Paris-Sud, UVSQ, CESP, Villejuif, F-94805 France
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5 INSERM Radiation Epidemiology Team, Villejuif, F-94805 France
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6 French military health service (SSA), Center for Epidemiology and Public Health of the French Army
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(CESPA), Camp de Sainte Marthe, F-13568 Marseille, France
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7 Aix-Marseille université, INSERM, IRD, SESSTIM (Sciences économiques & sociales de la santé & traitement
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de l’information médicale), Marseille, France.
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8 Institut de Cancérologie de l'Ouest, site René Gauducheau CLCC Nantes-Atlantique, Département de
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Recherche, Saint-Herblain, F-44800 France
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9 CHU d’Angers, Pediatric Oncology Department, F-49100 Angers, France
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Running title:
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Smoking and cannabis use among childhood cancer survivors
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Keywords:
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Cancer survivors health behavior tobacco smoking risk factors cohort study
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Financial support:
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This study was partially supported by the INCa/ARC foundation (CHART project), the Agence Nationale Pour
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la Recherche Scientifique (Hope-Epi project), the ARC foundation (Pop-HaRC project), the Ligue Nationale
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Contre le Cancer, and the Programme Hospitalier de Recherche Clinique. These funding agencies had no role in
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the design and conduct of the study, in the collection, management, analysis and interpretation of the data, or in
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the preparation, review, and approval of the manuscript.
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Corresponding author:
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Agnès Dumas
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10 avenue de Verdun. 75010 Paris
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agnes.dumas@inserm.fr, +33 157278626
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https://orcid.org/0000-0001-7948-6952
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Competing interest:
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The authors declare no competing interests.
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Word count: 4,265
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Number of figures: 1
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Number of tables: 4
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ABSTRACT
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Background. Unhealthy behaviors among childhood cancer survivors increase the risks for cancer treatment
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adverse effects. We aimed to assess tobacco and cannabis use prevalence in this population and to identify
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factors associated with these consumptions.
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Methods. This study involved 2,887 5-year survivors from the French childhood cancer survivor study (FCCSS)
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cohort. Data on health behaviors were compared with those of controls from the general population.
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Associations of current smoking and cannabis use with clinical features, sociodemographic characteristics and
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health-related quality of life (QOL) were investigated using multivariable logistic regressions.
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Results. Prevalence for tobacco use was lower in survivors (26%) than in controls (41%, P < 0.001). Among
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current smokers, survivors smoked more cigarettes per day and started at a younger age than controls. Women,
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college graduates, older, married and CNS tumour survivors, as well as those who received chemotherapy and
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thoracic radiation therapy, were less likely to be smokers and/or cannabis consumers than others. Participants
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with a poor mental QOL were more likely to smoke.
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Conclusions. Preventive interventions and cessation programs must be carried out as early as possible in
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survivors’ life, especially among young males with low educational level and poor mental health.
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Impact. This study brings new insights to health behaviors among childhood cancer survivors from a population
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with high rates of smoking and cannabis use.
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INTRODUCTION
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Cancer is the second leading cause of death during childhood.1 However, pediatric cancer survival has
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substantially increased over the past decades due to progress in therapy and diagnosis procedures, and five-years
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survival rates are now about 80% in Western countries.1 As a result of these improvements, a growing
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population of childhood cancer survivors (CCS) has emerged.
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However, survivors are more likely to experience further health complications than adults without pediatric
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cancer history because of organ toxicity induced by chemo- and radiotherapy late effects.2 Thirty years after the
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diagnosis of cancer, cumulative incidence of second malignant neoplasm and chronic health condition (including
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endocrine disorders, cardiovascular diseases, renal dysfunctions, musculoskeletal problems) may be over 70%
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among survivors2 who constitute a population at greater risk for morbidity and early mortality.36 Unhealthy
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behaviors, such as smoking, are preventable factors that are potentially prone to further increase the risk of
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second cancer and chronic health conditions in childhood cancer survivors who already have an excess risk due
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to their treatment. For instance, Travis et al.7 showed that smoking itself increased risk of subsequent lung cancer
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more than 20-fold in Hodgkin’s disease survivors, and that smoking appeared to further multiply risks from
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treatment with alkylating agents and/or radiotherapy. Therefore, CCS are strongly encouraged to adopt healthy
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lifestyles.
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Thus, smoking among survivors of childhood cancer is a major concern; there is a real need for data to assess the
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magnitude of this public health issue and investigate its determinants to develop targeted interventions and
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effective policies. Several studies have reported prevalence of smoking among CCS and have compared tobacco
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use between survivors and control subjects. While most highlighted lower prevalence of smoking among
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survivors,816 a few reported greater prevalence for smoking among survivors17,18 or no differences.19,20
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Concerning cannabis consumption, lower prevalence was found among CCS.11,19,21,22 As the majority of these
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studies took place in North America8,9,12,15,1720 or in the UK,10,14 their results may not be generalizable to other
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populations with different distribution of risk behaviors, and need to be supported by other data. No such study
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has yet been conducted in France, which has a much higher prevalence of tobacco smoking than the UK, the US
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and Canada according to WHO data.23 France also has the highest prevalence of cannabis use in Europe despite
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the fact that it is not legalized (punishable by 1 year in prison or a fine of up to € 3,750 at the time of the present
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study).24 It is worthwhile to explore the determinants of smoking/cannabis use among CCS from a population
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with high rates of tobacco smoking and cannabis use to determine whether these determinants are similar to
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those reported among CCS from countries with lower rates of tobacco smoking and cannabis use.
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In this context, we aimed (a) to compare cigarette smoking and cannabis consumption between survivors of
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childhood cancer and controls from the general population, and (b) to identify demographic, socioeconomic and
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clinical risk factors associated to these unhealthy behaviors.
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METHODS
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Study population
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This study is based on data of the FCCSS (French Childhood Cancer Survivor Study) cohort which aims to
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investigate the overall long-term outcomes of children and adolescents treated for cancer.25,26 Eligible subjects
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were five-year cancer survivors treated before reaching age 18 for a solid tumour or a lymphoma in five French
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centers between 1945 and 2000.
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The FCCSS cohort currently includes 7,670 subjects. Data on tumour type and treatment were extracted from
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medical records, as well as gender, date of birth and date of diagnosis. Second cancer and cardiovascular
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diseases (myocardial infarction, angina, heart failure, valvular diseases, cardiac arrhythmia, conduction disorder,
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and pericardial diseases) were ascertained from physician’s report or medical records. Epidemiological data,
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including health behavior (smoking and cannabis use), health-related quality of life (QOL) and demographic and
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socioeconomic characteristics were collected using a self-administered questionnaire derived from the US and
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the UK survivors’ cohorts.8,10 Questionnaires were sent in two waves: the first one, from 2005 onwards, involved
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survivors treated before 1985, and the second one, from 2010 onwards, involved survivors treated from 1986 to
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2000. Three-quarters of the questionnaires (75.5%) were filled between 2005 and 2011. Among the FCCSS
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subjects, 802 died before the 1st wave of questionnaires was sent out, 248 died before the 2nd wave of
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questionnaires was sent out and 1,697 had unknown current postal address. As a result, 5,023 subjects were
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contacted by postal mail to complete this questionnaire; of these, 3,293 (65.6%) answered the questionnaire, and
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2,887 (59.7%) answered all the items related to current smoking, current cannabis use, health-related QOL, and
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demographic and socioeconomic characteristics (Figure 1).
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The FCCSS study has been approved by the INSERM national ethics committee and the French National
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Agency regulating Data Protection (CNIL N°902287). Written informed consent was obtained from patients,
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parents or guardians according to national recognized ethical guidelines.
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Control population
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Control population data were extracted from the 2010 Health Barometer, a cross-sectional general population
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survey conducted in France between October 2009 and July 2010, as described elsewhere.27 Briefly, a
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representative random sample of the general population was drawn by randomly generating phone numbers to
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contact households then selecting one eligible individual aged 15-85 years within each household. Data on health
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behaviors and sociodemographic background were anonymously collected during a phone interview with a
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trained interviewer. The sample, which is representative of the French general population, accounted for 27,653
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persons. Smoking status was available for the entire sample, whereas information related to cannabis use was
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available for 22,736 persons (82.2%).
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To assure that FCCSS participants (“case group”) and general population sample (“control group”) were
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comparable regarding distributions by gender, age group (< 25, 25-29, 30-39, ≥ 40 years), educational level (less
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than High School, High School graduate, College graduate) and marital status (married,
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single/divorced/widowed), a frequency matching program28 using these four variables as matching factors was
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performed. As we selected a 1:1 case-control ratio, 2,887 persons from the general population survey were
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defined as “controls” and were included in this study.
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Outcome variables: Smoking status and cannabis use
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Ever smoking was defined as a binary variable (yes, no) using the question Have you ever smoked cigarettes
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regularly?”. Current smoking was defined as a binary variable (yes, no) using the question “Do you currently
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smoke cigarettes regularly?”. Subjects who had ever smoked cigarettes regularly but who did not currently
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smoke were considered as those who quit smoking. Current smokers were asked how many cigarettes they
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smoke per day, and their age at initiation; number of cigarettes smoked per day was considered as a discrete
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variable (< 10, 10-20, > 20) or as a continuous variable, and the age in years at smoking initiation as a discrete
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variable (< 14, 14-17, 18-21, 22) or as a continuous variable. Current cannabis use was defined as a binary
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variable “smoking regularly cannabis” (yes, no).
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Correlates under study
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Clinical predictors were childhood cancer type (classified according to the International Classification of
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Childhood Cancer29), decade of childhood cancer diagnosis (divided into four categories: < 1975, 19751984,
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19851994, 1995), age at childhood cancer diagnosis, chemotherapy (no, yes), thoracic radiation therapy (no,
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yes), second cancer (no, yes) and cardiovascular disease (no, yes).
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Demographic predictors included age (< 30, 30-39, ≥ 40 years) and marital status (being married, being
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single/divorced/widowed). Socioeconomic predictors included employment status and educational level, which
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was defined as the highest diploma obtained: below High School, High School graduate, or College graduate
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(bachelor or higher).
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Health-related QOL was assessed using the Medical Outcomes Short Form-36 (SF-36 version 2), for which
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validity and reliability in CCS has been previously established.30 Briefly, this questionnaire is made of eight
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physical and mental health subscales (physical functioning, bodily pain, role limitations caused by physical
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health problems, role limitations caused by personal or emotional health problems, general mental health, social
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functioning, vitality and general health perception) which can be summarized with a Physical and a Mental
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Component Summary score (PCS and MCS, respectively).31 Scores ranged from 0 to 100, with higher scores
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representing better levels of health. Based on a similar previous work,15 we categorized PCS and MCS scores
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into quartiles.
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Statistical analysis
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First, demographics, socioeconomics and clinical characteristics of CCS who answered the self-administered
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questionnaire were compared to those of non-respondents using chi-square tests. We compared health behavior
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characteristics of participants (smoking prevalence, number of cigarettes smoked per day, age at smoking
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initiation, and prevalence of current cannabis use) with those of sex-, age-, educational level- and marital status-
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matched controls from the general population, using chi-square tests and Mann-Whitney U tests.
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We compared the prevalence of current smoking/cannabis use between each type of childhood cancer group
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using a chi-square test of independence. We used modified Poisson regression models with robust errors to
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estimate relative risks (RRs) and 95% confidence intervals (CI) for current smoking and cannabis use in
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survivors of each childhood cancer type versus controls from the general population, with adjustment for
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demographic and socioeconomic variables (sex, age, educational level and marital status). We used modified
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Poisson regression rather than logistic regression because current smoking was common.32
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Then, factors associated with current smoking, smoking cessation and cannabis use among childhood cancer
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survivors were investigated using multivariate modified Poisson regression models with robust errors.
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Socioeconomic characteristics (gender, age, marital status, educational level, employment status), health-related
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QOL (MCS and PCS scores) and clinical features (childhood cancer type, age at diagnosis, cancer treatments,
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second cancer, cardiovascular disease) were all included as predictive variables to explore their associations with
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current smoking and cannabis use. To take into account the possible non-response bias, the models were also
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adjusted for a propensity score that estimated the propensity of response to the questionnaire within the FCCSS
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cohort: characteristics that differed between responders and non-responders (sex, childhood cancer type, age in
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years at first cancer, decade of diagnosis at first cancer, radiation therapy) were incorporated into this propensity
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score through a logit model to calculate the probability of response of each participant.26,33
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In addition, possible effect modification by CNS (central nervous system) tumour and thoracic radiation therapy
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was tested using multiplicative interaction terms to explore whether CNS tumour survivors and survivors treated
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with thoracic radiation therapy had different risk factors for smoking and cannabis use compared to their
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counterparts, as they are known to adopt healthier behaviors than other survivors.8,10
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All analyses were conducted using SAS 9.4 software (SAS Institute Inc., Cary, NC, USA). All P-values were
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two-sided; P-values <0.05 were considered as statistically significant.
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RESULTS
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Characteristics of participants
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Overall, response to the questionnaire was significantly associated with gender, cancer type, age at cancer,
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decade of diagnosis and radiation therapy (Table 1). About half of the responders (48.0%) were diagnosed under
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5 years of age. Most responders were diagnosed before 1995 (86.3%) whereas 52.8% of the non-responders were
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diagnosed from 1995 onwards. The most prevalent diagnoses were Wilms tumour (18.4%) and Neuroblastoma
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(14.3%). Retinoblastoma was the less common diagnosis among responders (4.5%), but the most frequent
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among non-responders (20.2%). About half of non-responders (48.4%) received radiation therapy, against 57.0%
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among the responders (Table 1). Mean age at study was 33.4 years. Overall, 20.2% of participants had an
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educational level below High School and 79.9% were not married.
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Smoking status and cannabis use: comparison between childhood cancer survivors and controls from the
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general population
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Smoking status and cannabis use in FCCSS participants and sex-, age-, education level- and marital status-
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matched controls from the general population are described in Table 2. Prevalence of current smoking was lower
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in CSS than in controls (25.9% vs 40.7%, P < 0.001), as well as prevalence of ever smoking (49.4% vs 56.6%, P
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< 0.001). Age at smoking initiation was lower in survivors (17.5 vs 18.5 years, P < 0.001). Among CCS, 677 of
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those who have ever smoked have quit smoking (47.5%). When smoking, participants smoked slightly more
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cigarettes per day than controls from general population (11.6 vs 11.0, P=0.016). Prevalence of current cannabis
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use was similar among survivors (6.6%) and controls (6.8%, P=0.676). Using a chi-square test, current smoking
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and current cannabis use among survivors were strongly associated (p<0.001, Supplementary Table S1).
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Survivors of each type of cancer were significantly less likely to smoke than the general population (Table 3).
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Survivors of CNS tumour had the lowest risk of smoking compared to the general population (RR 0.31, 95% CI
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0.24 to 0.42), whereas survivors of soft tissue sarcoma had the highest risk (RR 0.76, 95% CI 0.64 to 0.90).
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Regarding cannabis use, only the CNS tumour survivors were significantly less likely to consume cannabis than
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the general population (RR 0.35, 95% CI 0.17 to 0.71), while survivors of soft tissue sarcoma had the highest
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odds (RR 1.36, 95% CI 0.94 to 1.99) (Table 3).
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Factors associated with smoking among childhood cancer survivors
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Results of multivariable analysis examining associations between current smoking and clinical, demographic,
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socioeconomic and QOL predictors among survivors are presented in Table 4. Survivors of CNS tumour had a
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significantly lower risk of being current smokers compared to survivors of Wilms Tumour (RR 0.43, 95% CI
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0.31 to 0.59). Survivors who had received chemotherapy (RR 0.85, 95% CI 0.73 to 0.99), those who had
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received thoracic radiation therapy (RR 0.80, 95% CI 0.64 to 0.99), those who had a second cancer (RR 0.65,
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95% CI 0.44 to 0.96) and those who had a cardiovascular disease (RR 0.72, 95% CI 0.52 to 0.99) were less
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likely to be current smokers. No differences were found between smokers and non-smokers regarding age at first
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cancer. Current smokers were more likely to be males (RR 1.40, 95% CI 1.23 to 1.59) and less likely to be
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married (RR 0.82, 95% CI 0.69 to 0.97). Older survivors ( 40 years) were less likely to smoke than younger
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ones (< 30 years) (RR 0.78, 95% CI 0.62 to 0.99). Survivors who graduated from College were less likely to be
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current smokers than those who dropped out before High School (RR 0.59, 95% CI 0.50 to 0.70). Participants
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with a poor score for physical QOL (< 1st quartile) were less likely to be current smokers compared to others
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(RR 0.84, 95% CI 0.71 to 0.98). Conversely, survivors with a poor score for mental QOL (< 1st quartile) were
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more likely to smoke compared to those with a high score for mental QOL (> 3rd quartile) (RR 1.60, 95% CI
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1.34 to 1.91). We did not find any effect modification by CNS tumour or thoracic radiation therapy. Males where
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less likely to quit smoking (RR 0.82, 95% CI 0.73 to 0.92), whereas survivors who were married (RR 1.23, 95%
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CI 1.09 to 1.38), those with a high educational level (RR 1.45, 95% CI 1.24 to 1.70) and those who had a second
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cancer (RR 1.27, 95% CI 1.04 to 1.55) were more likely to quit.
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Factors associated with current cannabis use among childhood cancer survivors
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Survivors of CNS tumour had a significantly lower risk of being current cannabis users compared to survivors of
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Wilms Tumour (RR 0.35, 95% CI 0.16 to 0.80) (Table 4). No differences were found regarding thorax radiation
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therapy, chemotherapy, age at first cancer, second cancer and cardiovascular diseases. Cannabis users were more
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likely to be males (RR 2.81, 95% CI 2.06 to 3.82) and unemployed (RR 1.58, 95% CI 1.08 to 2.30). Cannabis
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use decreased with age: CCS aged 30-39 years and those aged 40 years or older were less likely to be current
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cannabis users than those under 30 years of age (RR 0.60, 95% CI 0.42 to 0.87, and RR 0.31, 95% CI 0.17 to
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0.57, respectively). Compared to survivors who dropped out before High School, those who graduated from
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College were less likely to be current cannabis users (RR 0.62, 95% CI 0.41 to 0.93). Participants with a poor
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score for mental health (< 1st quartile) were more likely to be current cannabis users compared to those with a
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high score for mental QOL (> 3rd quartile) (RR 1.95, 95% CI 1.20 to 2.92). We did not find any effect
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modification by CNS tumour or thoracic radiation therapy.
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DISCUSSION
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In this multicenter cohort study including a large number of long-term childhood cancer survivors, we found that
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the prevalence of current smoking in survivors (26%) was lower than in sex-, age-and educational level-matched
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controls from the general population (41%). However, survivors who smoked were prone to start at a younger
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age and to smoke more cigarettes per day than smokers from the general population. Prevalence of current
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cannabis use was similar in survivors and controls. We also identified several risk factors associated with current
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smoking and cannabis use.
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About half of survivors (49%) in the FCCSS study had ever smoked and 25% were current smokers, which is
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higher than the prevalence found in other cohorts of survivors. Indeed, prevalence of ever and current smoking
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were lower in the North American cohort (27% and 17%, respectively)8 and in the British cohort (30% and 20%,
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respectively).10 These differences may reflect substantial discrepancies in smoking habits between countries, as
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suggested by WHO data showing that age-standardized prevalence of tobacco smoking is much higher in France
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than in the U.K., the U.S. or Canada.23 Nevertheless, in our study, survivors smoked less than controls, which is
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in line with what have been found in the North American and the British cohorts,8,10 and in most of the previous
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studies.11,12,14,16 Conversely, two other U.S. studies17,18 reported that survivors were more likely to be current
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smokers than controls and had especially high smoking rates (35-37%). It should be noted that, in these studies,
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the current smoking group included both regular and occasional smokers. Overall, differences in survivors’
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characteristics (e.g., nationality, age, socioeconomic status) and in smoking status definition could contribute to
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conflicting results between studies regarding smoking rates.
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Early onset of smoking is of particular concern since it increases the risk for developing related morbidities
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(such as cardiovascular diseases and lung cancer) and affects all-cause mortality.34 In our study, age of smoking
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initiation among childhood cancer survivors was 17.5 years. Similar age of initiation (17.4 years) was reported in
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the British cohort.10 Alarmingly, we found that survivors initiated smoking at a younger age than controls from
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the general population, which differ from results of British and Swiss studies.10,16 It is well-known that an early
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age of smoking initiation is associated with a heavier smoking in adulthood;35 thus, it is not surprising that we
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also reported that FCCSS survivors smoked more cigarettes per day than controls (11.3 vs 9.3). However,
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survivors from the British cohort smoked less cigarettes than controls from the general population (11.8 vs
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14.3).10
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Overall, determinants of tobacco smoking among French survivors from our study were also reported in other
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studies from other countries with different rates of smoking, suggesting that risk factors for smoking in CCS may
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be similar across countries, regardless of the country's smoking pattern. We found that the survivors of
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childhood CNS tumors had a lower risk of being current smokers, as previously suggested in other cohort
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studies.8,10 Since survivors of CNS malignancies are prone to suffer from permanent neurocognitive
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impairment,36 partly because of their treatment, it has been hypothesized that these survivors must be very
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dependent on others, which should prevent them from having the opportunity to initiate smoking.8,10
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The risks of second cancer and chronic health conditions are known to be increased by radiation therapy and
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chemotherapy2 and must be further multiplied by health behaviors, including current smoking.7 Therefore, it is
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reassuring that FCCSS survivors who underwent thoracic radiation therapy and chemotherapy were less likely to
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be current smokers, consistently with findings reported by Frobisher et al.10 It is possible that the “cancer
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experience” of these survivors was more intense, and thus they may be more engaged with cancer survivorship
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and its emphasis of healthier lifestyles. Our results regarding demographic and socioeconomic factors associated
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with smoking among childhood cancer survivors indicated that women, college graduates, older (≥ 40 years old),
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and married participants were less likely to be current smokers. Similar relationships were reported in several
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other studies,15,17 including the North American8 and the UK10 cohorts. Sociodemographic predictors of current
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smoking reported in survivors also corresponded to those found in the French population,37 and it has been
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recognized that survivors are no different from their peers in regard to sociodemographic factors associated with
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being a smoker.8,10,15,16
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To our knowledge, only one study investigated the association between QOL and smoking in survivors, and this
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study found no significant associations.15 We showed that poorer mental health was related to smoking, which
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echoes what has been found in the general population.37,38 Nevertheless, the direction of the relationship is
315
difficult to determine because we only had SF-36 measures at the time of the questionnaire, and not at the time
316
of smoking initiation. In general population, several studies reported that baseline depression or anxiety was
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associated with later smoking, while some others supported the alternative hypothesis that smoking at baseline
318
increases susceptibility to poor mental health condition.39
319
More surprisingly, FCCSS survivors with a poor physical score (PCS score < 1st quartile) were less likely to
320
being current smokers than survivors with greater physical health. This finding may be the consequence of
321
serious and disabling sequelae of cancers such as bone sarcomas or CNS tumors which may keep them from
322
having unhealthy behaviors (e.g., amputation or psychomotor disorders). Furthermore, we found that survivors
323
with comorbidities such as second cancer and cardiovascular were less likely to be current smokers, which
324
supports the hypothesis that poor health condition may prevent current smoking.
325
Compared to tobacco use, cannabis use is poorly documented among childhood cancer survivors. Few authors
326
reported that survivors were less likely to consume cannabis but these studies were conducted only in
327
adolescents/young adults11,22 or among a very small number of participants.19,22 We did not find any difference
328
between FCCSS participants and controls from general population concerning current cannabis use. Predictors
329
related to cannabis use in our study were very similar to those related to current smoking. Poor mental health
330
condition was strongly associated with being current cannabis users, in line with findings from Milam et al.22
331
showing that higher depressive symptoms were related to marijuana use in survivors.
332
The present study had a few limitations. The FCCSS did not include survivors of leukemia; survivors of solid
333
tumors or lymphoma were recruited in five French centers, therefore proportion of each type of cancer in our
334
sample may not fully represent the proportion of each type of cancer in the whole French population. Despite the
335
fact that about one third of the eligible survivors in FCCSS did not answer the questionnaire, almost 3,000
336
participants have been involved in the present study. Several differences were found between responders and
337
non-responders regarding gender and clinical characteristics which could slightly distort the prevalence of
338
smoking and cannabis use reported in this study. Nevertheless, this potential non-response bias was taken into
339
account in our etiological analyses since the models investigating risk factors of current smoking/cannabis use
340
and smoking cessation were adjusted for a propensity score that estimated the propensity of response to the
341
questionnaire within the FCCSS cohort.26,33
342
Smoking status and cannabis use were self-reported using a questionnaire and thus were subject to reporting
343
bias. As a result, prevalence of smoking and number of cigarettes smoked per day may have been somewhat
344
underestimated due to a known tendency to underreport unhealthy behaviors (or over report healthy behaviors)
345
in health surveys.40 However, studies conducted elsewhere also relied on responses to questionnaire rather than
346
on biomarkers measurements, which allows comparison across studies. Smoking and cannabis prevalence data in
347
FCCSS was collected from 2005 to the mid-2010s, whereas health behaviors data in general population was
348
from a large nationally representative survey conducted during the year 2010. Fortunately, prevalence of
349
smoking and cannabis use over the period of data collection remained relatively stable in France.41,42
350
One strength of this work was that controls from the general population were sex-, age-, educational level- and
351
marital status-matched with FCCSS participants. Matching by gender and/or by age was common in other
352
similar studies, unlike matching on educational level and marital status, although these two sociodemographic
353
predictors are highly correlated to tobacco or cannabis use, in the general population43,44 as well as in childhood
354
cancer survivors.10 Our study is one of the few to compare simultaneously smoking prevalence, age at initiation
355
and number of cigarettes smoked per day between survivors and controls from the general population. Another
356
strength was that physical and mental health-related QOL were considered as potential predictors of health
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10
behaviors in our analyses using the SF-36, a validated measure of QOL, which was the case in only one other
358
study.15
359
In conclusion, this large study brings important information about smoking and cannabis use among childhood
360
cancer survivors. Overall, survivors of childhood cancer had lower smoking rates than the general population,
361
whereas cannabis use prevalence was similar among survivors and the general population. Especially, survivors
362
who received chemotherapy and/or thoracic radiation therapy, and therefore had an increased risk of second
363
cancer and chronic health conditions, were less likely to be smokers. Nevertheless, smokers among survivors
364
started smoking at a younger age and smoked more cigarettes per day than smokers from the general population.
365
Thus, it is crucial to identify them at early age and to implement strategies to help them quit smoking, as well as
366
to carry out preventive interventions as early as possible in survivors’ life. The identification of factors
367
associated with these health behaviors gives clinicians few keys to adapt their recommendations to the profile of
368
their patients: young survivors, males, those with low socioeconomic status and those with poor mental health
369
condition must be especially targeted by multiple interventions to reduce smoking and cannabis use.
370
371
ACKNOWLEDGEMENTS
372
We thank the patients and all the clinicians and research staff who participated in the study. We are grateful to
373
Françoise Terrier, Isao Kobayashi, Amel Boumaraf and Martine Labbé for their contribution to this work.
374
375
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TABLES
516
517
Table 1. Demographic, socioeconomic and clinical characteristics of responders (N=3,293) and non-responders
(N=1,730) in the FCCSS cohort.
Non-responders
n (%)
p-valuea
Clinical characteristics
Childhood cancer type
Wilms Tumour
173 (10.0%)
< 0.001
Neuroblastoma
212 (12.3%)
Hodgkin's lymphoma
99 (5.7%)
Non-Hodgkin's lymphoma
137 (7.9%)
Soft tissue sarcoma
151 (8.7%)
Bone sarcoma
157 (9.1%)
CNS tumour
237 (13.7%)
Retinoblastoma
350 (20.2%)
Other solid cancersb
214 (12.4%)
Age in years at first cancer
< 5
957 (55.3%)
< 0.001
5-9
320 (18.5%)
10-14
306 (17.7%)
≥ 15
147 (8.5%)
Decade of diagnosis of first cancer
< 1975
57 (3.3%)
< 0.001
1975 - 1984
104 (6.0%)
1985 - 1994
656 (37.9%)
≥ 1995
913 (52.8%)
Chemotherapy
No
400 (23.1%)
0.156
Yes
1,330 (76.9%)
Thoracic radiation therapy
No
1,569 (90.7%)
< 0.001
Yes
161 (9.3%)
Second cancer
No
-
Yes
-
Cardiovascular
disease
No
-
Yes
-
Demographic and socioeconomic characteristics
Sex
Males
963 (55.7%)
< 0.001
Females
767 (44.3%)
Age in years at the questionnaire
< 25
-
25-29
-
30-39
-
≥ 40
-
Educational level
Less than High School
-
High School graduate
-
College graduate
-
Unemployed and seeking work
No
-
Yes
-
Marital status
Single, divorced or widowed
-
Married
-
CNS, central nervous system.
a Chi-square test.
b Gonadal tumour, thyroid tumour and other types of carcinoma.
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519
Table 2. Smoking status and cannabis use in childhood cancer survivors from the FCCSS cohort (N=2,887)
compared with sex-, age-, education level- and marital status-matched controls from the general population.
Survivors
Controls
p-value
Ever smoking, n (%)
< 0.001a
No
1,459 (50.6%)
1,253 (43.4%)
Yes
1,424 (49.4%)
1,633 (56.6%)
Current smoking, n (%)
< 0.001a
No
2,140 (74.1%)
1,711 (59.3%)
Yes
747 (25.9%)
1,176 (40.7%)
- Age in years at smoking initiation, mean ± SD
17.5 ± 3.6
18.5 ± 4.0
< 0.001b
- Age in years at smoking initiation, n (%)
< 0.001a
< 14
35 (4.9%)
32 (3.4%)
14-17
406 (56.3%)
378 (40.1%)
18-21
213 (29.5%)
403 (42.7%)
22
67 (9.3%)
130 (13.8%)
- Number of cigarettes smoked per day, mean ± SD
11.6 ± 7.8
11.0 ± 8.9
0.016b
- Number of cigarettes smoked per day, n (%)
0.028a
<10
284 (39.1%)
503 (43.0%)
10-20
391 (53.9%)
561 (47.9%)
>20
51 (7.0%)
107 (9.1%)
Current cannabis use, n (%)
0.676a
No
2,698 (93.5%)
2,539 (93.2%)
Yes
189 (6.6%)
186 (6.8%)
SD, standard deviation.
a Chi-square test.
b Mann-Whitney U Test.
520
521
522
523
524
525
526
527
528
529
530
531
532
533
534
535
536
537
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16
Table 3. Prevalence and odds ratios for being current smoker and current cannabis user among childhood
cancer survivors (overall and by cancer type) from the FCCSS cohort (N=2,887) compared to the general
population.
Current smokers
Current cannabis users
%
RRa [95% CI]
%
RRa [95% CI]
FCCSS overall
25.9%
0.64 [0.59-0.68]
6.6%
1.00 [0.82-1.21]
Wilms Tumour
27.8%
0.70 [0.60-0.80]
5.9%
0.93 [0.65-1.33]
Neuroblastoma
28.8%
0.68 [0.58-0.80]
8.0%
1.04 [0.74-1.48]
Hodgkin's lymphoma
21.7%
0.55 [0.42-0.73]
5.7%
1.02 [0.57-1.84]
Non-Hodgkin's lymphoma
28.6%
0.70 [0.59-0.83]
7.6%
1.11 [0.76-1.64]
Soft tissue sarcoma
29.9%
0.76 [0.64-0.90]
8.1%
1.36 [0.94-1.99]
Bone sarcoma
25.2%
0.66 [0.54-0.81]
5.8%
1.10 [0.68-1.79]
CNS tumour
14.3%
0.31 [0.24-0.42]
2.8%
0.35 [0.17-0.71]
Retinoblastoma
22.7%
0.51 [0.37-0.70]
7.0%
0.80 [0.42-1.54]
Other solid cancers
26.4%
0.69 [0.58-0.82]
7.4%
1.32 [0.90-1.95]
Chi-square test of independence
p<0.001
p=0.159
CNS, central nervous system; FCCSS, French childhood cancer survivor study; RR, relative risk.
a Relative risks ratios were adjusted for sex, age, educational level and marital status.
538
539
540
541
542
543
544
545
546
547
548
549
550
551
552
553
554
555
556
557
558
559
560
561
562
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17
563
Table 4. Demographic, socioeconomic, health-related quality of life, and clinical factors related to current smoking,
smoking cessation and current cannabis use in childhood cancer survivors from the FCCSS cohort.
Current smoking
Smoking cessation
Current cannabis use
N=2,887
N=1,424
N=2,887
RRa [95% CI]
RRa [95% CI]
RRa [95% CI]
Clinical characteristics
Childhood cancer
type
Wilms Tumour
1
1
1
Neuroblastoma
1.00 [0.81-1.22]
0.90 [0.75-1.09]
1.22 [0.77-2.95]
Hodgkin's lymphoma
1.03 [0.72-1.45]
0.91 [0.70-1.19]
1.07 [0.49-2.31]
Non-Hodgkin's lymphoma
1.02 [0.81-1.28]
0.85 [0.68-1.07]
1.09 [0.66-1.80]
Soft tissue sarcoma
1.13 [0.91-1.40]
0.86 [0.71-1.06]
1.46 [0.90-2.37]
Bone sarcoma
1.08 [0.82-1.42]
0.99 [0.79-1.24]
1.19 [0.62-2.30]
CNS tumour
0.43 [0.31-0.59]
1.05 [0.80-1.37]
0.35 [0.16-0.80]
Retinoblastoma
0.73 [0.51-1.04]
1.25 [0.91-1.72]
0.94 [0.43-2.06]
Other solid cancersb
0.96 [0.75-1.23]
0.95 [0.77-1.18]
1.39 [0.82-2.37]
Age in years at
first cancer
< 5
1
1
1
5-9
0.88 [0.73-1.05]
1.08 [0.92-1.27]
1.06 [0.72-1.56]
10
0.96 [0.79-1.17]
1.13 [0.94-1.35]
1.09 [0.70-1.70]
Chemotherapy
No
1
1
1
Yes
0.85 [0.73-0.99]
0.98 [0.86-1.13]
1.08 [0.73-1.60]
Thoracic radiation
therapy
No
1
1
1
Yes
0.80 [0.64-0.99]
1.09 [0.94-1.28]
0.89 [0.54-1.47]
Second cancer
No
1
1
1
Yes
0.65 [0.44-0.96]
1.27 [1.04-1.55]
1.12 [0.55-2.25]
Cardiovascular
disease
No
1
1
1
Yes
0.72 [0.52-0.99]
1.17 [0.95-1.43]
0.82 [0.42-1.58]
Demographic and socioeconomic characteristics
Sex
Females
1
1
1
Males
1.40 [1.23-1.59]
0.82 [0.73-0.92]
2.81 [2.06-3.82]
Age in years at
the questionnaire
< 30
1
1
1
30-39
0.98 [0.82-1.16]
1.09 [0.92-1.28]
0.60 [0.42-0.87]
40
0.78 [0.62-0.99]
1.19 [0.97-1.46]
0.31 [0.17-0.57]
Educational level
Less than High School
1
1
1
High School graduate
0.88 [0.75-1.03]
1.09 [0.92-1.29]
0.94 [0.65-1.37]
College graduate
0.59 [0.50-0.70]
1.45 [1.24-1.70]
0.62 [0.41-0.93]
Unemployed and
seeking work
No
1
1
1
Yes
1.20 [0.99-1.45]
1.07 [0.89-1.28]
1.58 [1.08-2.30]
Marital status
Single, divorced or widowed
1
1
1
Married
0.82 [0.69-0.97]
1.23 [1.09-1.38]
0.72 [0.48-1.08]
Health-related quality of life
SF-36 MCS score
< Q1 (38.7)
1.60 [1.34-1.91]
0.86 [0.74-1.00]
1.95 [1.30-2.92]
Q1 (38.7) median (46.8)
1.26 [1.05-1.51]
0.93 [0.80-1.08]
1.54 [1.03-2.29]
Median (46.8) Q3 (53.0)
1.13 [0.94-1.37]
0.98 [0.85-1.15]
1.21 [0.79-1.85]
> Q3 (53.0)
1
1
1
SF-36 PCS score
< Q1 (46.4)
0.84 [0.71-0.98]
1.12 [0.99-1.27]
0.86 [0.60-1.24]
> Q1 (46.4)
1
1
1
CI, confidence interval; CNS, central nervous system; MCS, Mental Component Summary; PCS, Physical Component Summary;
Q1, 1st quartile; Q3, 3rd quartile; RR, relative risk.
a Relative risks were adjusted for all the covariates presented in the table and for the propensity of response to the questionnaire.
b gonadal tumour, thyroid tumour and other types of carcinoma.
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18
565
FIGURES
566
567
Figure 1. Flow-chart of the FCCSS cohort subjects participating in the present study.
568
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Published OnlineFirst July 28, 2021.Cancer Epidemiol Biomarkers Prev
Nicolas Bougas, Brice Fresneau, Sandrine Pinto, et al.
Study
survivors: results of the French Childhood Cancer Survivor
Smoking and cannabis use among childhood cancer
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Only a few small studies have assessed the long-term morbidity that follows the treatment of childhood cancer. We determined the incidence and severity of chronic health conditions in adult survivors. The Childhood Cancer Survivor Study is a retrospective cohort study that tracks the health status of adults who received a diagnosis of childhood cancer between 1970 and 1986 and compares the results with those of siblings. We calculated the frequencies of chronic conditions in 10,397 survivors and 3034 siblings. A severity score (grades 1 through 4, ranging from mild to life-threatening or disabling) was assigned to each condition. Cox proportional-hazards models were used to estimate hazard ratios, reported as relative risks and 95% confidence intervals (CIs), for a chronic condition. Survivors and siblings had mean ages of 26.6 years (range, 18.0 to 48.0) and 29.2 years (range, 18.0 to 56.0), respectively, at the time of the study. Among 10,397 survivors, 62.3% had at least one chronic condition; 27.5% had a severe or life-threatening condition (grade 3 or 4). The adjusted relative risk of a chronic condition in a survivor, as compared with siblings, was 3.3 (95% CI, 3.0 to 3.5); for a severe or life-threatening condition, the risk was 8.2 (95% CI, 6.9 to 9.7). Among survivors, the cumulative incidence of a chronic health condition reached 73.4% (95% CI, 69.0 to 77.9) 30 years after the cancer diagnosis, with a cumulative incidence of 42.4% (95% CI, 33.7 to 51.2) for severe, disabling, or life-threatening conditions or death due to a chronic condition. Survivors of childhood cancer have a high rate of illness owing to chronic health conditions.
Article
Because of their increased risk for second cancers, childhood cancer survivors are people who really should not smoke, but available evidence suggests that they do. We studied the smoking habits of long-term childhood cancer survivors in data collected from 1289 adult survivors of childhood cancer and 1930 of their sibling controls. Survivors were diagnosed with cancer between 1945 and 1974 when they were less than 20 years old. Using matched analyses that controlled for the influence of family, survivors were 8% less likely than controls to be current smokers, 13% less likely to be eversmokers, but 12% less likely to have quit smoking; these differences were not statistically significant. In a logistic regression analysis there was a significant difference by year of diagnosis for current smoking rate ratios (RR); survivors were less likely to be current smokers if diagnosed in recent years (RR = 0.76; 95% confidence intervals = 0.58–0.98, between 1965–74) and quite similar to controls if diagnosed in earlier years (RR = 1.05 between 1945 and 1954). In our group of long-term cancer survivors, the reduction in current smoking came about because survivors were more inclined never to start smoking than controls. Once addicted to tobacco, they were less likely to quit. While the fact that survivors are less likely to start smoking is encouraging, the persistence of smoking habits strongly suggests the need for continuing efforts to prevent smoking in this most vulnerable group.
Article
Age-adjusted mortality rates are higher for the unmarried and nonparents than for the married and parents. The effects of marital and parental status on mortality are usually attributed to the positive effects of social integration or social support. The mechanisms by which social support or integration is linked to health outcomes, however, remain largely unexplored. One mechanism may involve health behaviors; the family relationships of marriage and parenting may provide external regulation and facilitate self-regulation of health behaviors which can affect health. The present study employs a national sample to examine the relationships of marital and parenting status to a variety of health behaviors. Results indicate that marriage and presence of children in the home have a deterrent effect on negative health behaviors. It is suggested, within the theoretical framework of social integration, that family roles promote social control of health behaviors which affect subsequent mortality.
Article
Survivors of childhood and adolescent cancer are at risk for long-term effects of disease and treatment. The Childhood Cancer Survivor Study assessed overall and cause-specific mortality in a retrospective cohort of 20,227 5-year survivors. Eligible subjects were individuals diagnosed with cancer (from 1970 to 1986) before the age of 21 who had survived 5 years from diagnosis. Underlying cause of death was obtained from death certificates and other sources and coded and categorized as recurrent disease, sequelae of cancer treatment, or non-cancer-related. Age and sex standardized mortality ratios (SMRs) were calculated using United States population mortality data. The cohort, including 208,947 person-years of follow-up, demonstrated a 10.8-fold excess in overall mortality (95% confidence interval, 10.3 to 11.3). Risk of death was statistically significantly higher in females (SMR = 18.2), individuals diagnosed with cancer before the age of 5 years (SMR = 14.0), and those with an initial diagnosis of leukemia (SMR = 15.5) or CNS tumor (SMR = 15.7). Recurrence of the original cancer was the leading cause of death among 5-year survivors, accounting for 67% of deaths. Statistically significant excess mortality rates were seen due to subsequent malignancies (SMR = 19.4), along with cardiac (SMR = 8.2), pulmonary (SMR = 9.2), and other causes (SMR = 3.3). Treatment-related associations were present for subsequent cancer mortality (radiation, alkylating agents, epipodophyllotoxins), cardiac mortality (chest irradiation, bleomycin), and other deaths (radiation, anthracyclines). No excess mortality was observed for external causes (SMR = 0.8). While recurrent disease remains a major contributor to late mortality in 5-year survivors of childhood cancer, significant excesses in mortality risk associated with treatment-related complications exist up to 25 years after the initial cancer diagnosis.
Article
This cross-sectional study collected baseline data on the health behaviours of a large population of survivors of childhood cancer in the UK, aged 18–30 years, compared with those of sex- and age-matched controls. Data from 178 young adult survivors of childhood cancer, diagnosed and treated at Bristol Children's Hospital, 184 peers from the survivors' GP practices and 67 siblings were collected by postal questionnaire. Conditional logistic regression analysis showed that, for matched sets of survivors and controls, survivors of a variety of childhood cancers reported lower levels of alcohol consumption (P=0.005), lower levels of cigarette smoking (P=0.027) and lower levels of recreational drug use (P=0.001) than controls. Analysis of matched sets of survivors and siblings showed similar trends but no significant differences. A health behaviour index for each participant was constructed from the data collected on five key health behaviours which influence future health status. Comparison of the means for each case group showed that survivors of childhood cancer were leading healthier lives than controls or siblings. This finding was expressed most clearly as the difference in the means of the health behaviour index for each case group, derived from five health behaviours (one-way ANOVA, P<0.001). British Journal of Cancer (2002) 87, 1204–1209. doi:10.1038/sj.bjc.6600632 www.bjcancer.com © 2002 Cancer Research UK
Epidemiology of childhood cancer
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Kaatsch P. Epidemiology of childhood cancer. Cancer Treat Rev 2010;36(4):912-918.
Cause-specific late 13
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Smoking and binge drinking 411
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Carswell K, Chen Y, Nair RC, Shaw AK, Speechley KN, Barrera M, et al. Smoking and binge drinking 411
among Canadian survivors of childhood and adolescent cancers: a comparative, population-based study
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