Investigation of Fusobacterium Nucleatum in saliva and colorectal mucosa: a pilot study.

As evidence has been linking the oral bacterium Fusobacterium nucleatum (F. nucleatum) to colorectal tumorigenesis, we aimed to produce preliminary data on the expression of F. nucleatum in both oral and colorectal body sites in cases diagnosed with colorectal neoplasms (CRN) and CRN-free controls. We conducted a pilot hospital-based case-control study among patients who underwent colonoscopy examination. Saliva samples and biopsies from healthy colon mucosa from CRN cases and CRN-free controls, and from tumors in cases, were collected, as well as data on periodontal condition and potential CRN risk factors. A total of 22 CRN cases and 21 CRN-free controls participated in this study, with a total of 135 biospecimens collected and analyzed by qPCR for detection and quantification of F. nucleatum. The detection rate of F. nucleatum was 95% in saliva samples and 18% in colorectal mucosa specimens. The median (95% CI) salivary F. nucleatum level was 0.35 (0.15-0.82) and 0.12 (0.05-0.65) in case and control groups, respectively, with a Spearman correlation of 0.64 (95% CI 0.2-0.94) between F. nucleatum level in saliva and healthy colorectal mucosa in controls. Our study results support the need for and the feasibility of further studies that aim to investigate the association between oral and colorectal levels of F. nucleatum in CRN cases and controls.Clinical Relevance: Considering the current evidence linking F. nucleatum to colorectal carcinogenesis, investigating the role of oral F. nucleatum expression in its colorectal enrichment is crucial for colorectal cancer screening and prevention avenues.

Targeting cancer stem cells with antibiotics inducing mitochondrial dysfunction as an alternative anticancer therapy.

Traditional cancer treatments based on chemo- and/or radiotherapy effectively kill only differentiated cancer cells, while metastasis and recurrences are caused by surviving cancer resistant cells (CRC) or a special subpopulation of cancer cells known as cancer stem cells (CSC). Both of these cell types compromise anticancer treatment through various mechanisms, including withdrawal of the anticancer drug through ATP-binding cassette transporters, increased expression of DNA repair genes, or transition to a quiescent phenotype. In contrast to many cancers, where energy consumption is due to glycolysis (Warburg effect), the bioenergetics of CSC and CRC is most often related to oxidative phosphorylation, that is, dependent on mitochondrial function. Therefore, compounds that induce mitochondrial dysfunction (MDF), such as some antibiotics, may represent an alternative approach to anticancer therapy. This review summarizes the major recent works on the use of antibiotics to target tumors via CSC and suggests next steps for developing this approach.

Periodontal disease as a risk factor for sporadic colorectal cancer: results from COLDENT study.

Colorectal cancer remains the top leading cancer worldwide. Accumulating evidence suggests periodontal pathogens are involved in colorectal carcinogenesis, indicating the need for high-quality epidemiological evidence linking periodontal disease (PD) and colorectal cancer (CRC). Thus, we conducted the first population-based case-control study that was specifically designed to investigate the association between compromised oral health and sporadic CRC. A total of 348 incident cases of colon or rectal cancer, and 310 age and sex frequency-matched controls, from the Montreal island and Laval population participated in the study. Data were collected on PD and on several CRC risk factors using validated questionnaires. A life-course approach was used to document long-term history regarding lifestyle factors. Multivariable unconditional logistic regression analysis was used to estimate the rate ratio (RR) quantifying the association between CRC and PD. Results showed that the rate of new diagnosis of CRC in persons with a positive history of PD was 1.45 times higher than in those with a negative history of PD adjusting for age, sex, BMI, education, income, diabetes, family history of CRC, regular use of non-steroidal anti-inflammatory drugs, lifetime cumulative smoking, lifetime consumption of red meats, processed meats, and alcoholic drinks, and lifetime total physical activity score (adjusted RR = 1.45; 95% CI 1.04-2.01; p = 0.026). Our results support the hypothesis of an association between PD and sporadic CRC risk.

Propensity score matching versus coarsened exact matching in observational comparative effectiveness research.

Aim & methods: We compared propensity score matching (PSM) and coarsened exact matching (CEM) in balancing baseline characteristics between treatment groups using observational data obtained from a pan-Canadian prostate cancer radiotherapy database. Changes in effect estimates were evaluated as a function of improvements in balance, using results from randomized clinical trials to guide interpretation. Results: CEM and PSM improved balance between groups in both comparisons, while retaining the majority of original data. Improvements in balance were associated with effect estimates closer to those obtained in randomized clinical trials. Conclusion: CEM and PSM led to substantial improvements in balance between comparison groups, while retaining a considerable proportion of original data. This could lead to improved accuracy in effect estimates obtained using observational data in a variety of clinical situations.

Detection of Fusobaterium nucleatum in feces and colorectal mucosa as a risk factor for colorectal cancer: a systematic review and meta-analysis.

BACKGROUND: Colorectal cancer (CRC) is a major cause of cancer deaths worldwide. Accumulating evidence suggests a potentially important role of colorectal infection with Fusobacterium nucleatum (F. nucleatum) in colorectal carcinogenesis. We conducted a systematic review, including both a qualitative synthesis and a meta-analysis, to synthesize the evidence from the epidemiological literature on the association between F. nucleatum detection in the colon/rectum and CRC. METHODS: A systematic literature search of Ovid MEDLINE(R), Embase, Web of Science Core Collection, EBM Reviews-Cochrane Database of Systematic Reviews, and CINAHL Plus with Full Text was conducted using earliest inclusive dates up to 4 October 2020. Eligible studies were original, comparative observational studies that reported results on colorectal F. nucleatum detection and CRC. Two independent reviewers extracted the relevant information. Odds ratio (OR) estimates were pooled across studies using the random effects model. Newcastle-Ottawa scale was used to critically appraise study quality. RESULTS: Twenty-four studies were included in the systematic review, of which 12 were included in the meta-analysis. Studies investigated F. nucleatum in feces, colorectal tissue samples, or both. In most studies included in the systematic review, the load of F. nucleatum was higher, on average, in specimens from CRC patients than in those from CRC-free controls. Meta-analysis showed a positive association between F. nucleatum detection in colorectal specimens and CRC (OR = 8.3; 95% confidence interval (95% CI) 5.2 to 13.0). CONCLUSIONS: The results of this systematic review suggest that F. nucleatum in the colon/rectum is associated with CRC. SYSTEMATIC REVIEW REGISTRATION: This systematic review protocol has been registered with the International Prospective Register of Systematic Reviews (PROSPERO) on July 10, 2018 (registration number CRD42018095866).

Is a fusobacterium nucleatum infection in the colon a risk factor for colorectal cancer?: a systematic review and meta-analysis protocol.

BACKGROUND: Despite a considerable amount of epidemiological research for identification of risk factors involved in the development of colorectal cancer, the current understanding of the etiology of this disease remains rather poor. Accumulating evidence suggests a potentially important role of infection with Fusobacterium nucleatum in the colon in colorectal carcinogenesis. The objective of this systematic review is to synthesize the epidemiological evidence on the association between infection with Fusobacterium nucleatum in the colon and colorectal cancer. METHODS: This systematic review will include observational studies (cohort, case-control, cross-sectional) in humans in which the role of Fusobacterium nucleatum in the etiology of colorectal cancer was investigated. MEDLINE, EMBASE, Web of Science, and Cochrane Database of Systematic Reviews will be searched using a comprehensive search strategy and manual screening of references. Two reviewers will independently identify eligible studies and extract the data from the included studies. The quality of studies will be assessed by using the Newcastle-Ottawa scale. Random-effects models will be used to estimate pooled measures of association (where feasible). Meta-regression and subgroup analyses will be conducted to explore the potential sources of heterogeneity. The Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement will be followed for reporting. DISCUSSION: Deepening knowledge regarding the etiology of colorectal cancer and the potential implications of Fusobacterium nucleatum in this disease is instrumental for prevention, diagnosis, and treatment of this often-fatal disease. This review will produce summarized current evidence on this topic. SYSTEMATIC REVIEW REGISTRATION: This systematic review protocol has been registered with the International Prospective Register of Systematic Reviews (PROSPERO) on 10 July 2018 (registration number CRD42018095866).

Does the use of incretin-based medications increase the risk of cancer in patients with type-2 diabetes mellitus?

PURPOSE: Incretin-based medications are a novel class of agents for the treatment of type-2 diabetes mellitus (DM2). The safety profile of these medications is not firmly established, and concerns have been raised about their potential carcinogenicity. The objective of our study was to produce new evidence on the effect of incretin-based medications on cancer risk in patients with DM2. METHODS: We conducted a "retrospective cohort" study with data from the Clinical Practice Research Datalink and the Hospital Episodes Statistics in the UK. New users of either an incretin-based medication (n = 18 885) or a sulfonylurea medication (n = 36 929) between 2007 and 2013 were identified and followed for up to 8 years. Cox proportional-hazards models were used to estimate the quasi-intention-to-treat and quasi-per-protocol hazard-ratios for the association between incretin-based medications with cancer while adjusting for potential confounders. RESULTS: The adjusted hazard ratio (95% confidence interval) for use of incretin-based medications versus use of sulfonylurea medications for the overall-cancer outcome was 0.97 (0.90, 1.05) in the quasi-intention-to-treat analysis and 0.90 (0.81, 1.00) in the quasi-per-protocol analysis. In both analyses, the hazard-ratio functions over the 8-year follow-up seemed fairly constant, and the 8-year cumulative-risk functions in the two subcohorts were similar. CONCLUSIONS: Our study suggests that the use of incretin-based medications in patients with DM2 does not increase the risk of cancer relative to the use of sulfonylurea medications, at least in the first several years of the use. Further research is needed to assess long-term effects of the use of incretin-based medications on cancer risk.

The consumption of coffee and black tea and the risk of lung cancer.

PURPOSE: Coffee and black tea are among the most consumed beverages worldwide. Although their potential role in lung cancer occurrence has been investigated in several studies, results have been inconclusive. We investigated the associations between intake of coffee and black tea with lung cancer in a population-based case-control study in Montreal, Canada. METHODS: These analyses included 1130 cases and 1483 controls. Adjusted odds ratios (ORs) were estimated between four metrics of coffee and black tea consumption (frequency, average daily amount, duration, and cumulative amount) and lung cancer, using unconditional logistic regression. RESULTS: The adjusted ORs (95% confidence intervals) for lung cancer comparing daily to never consumers were 0.73 (0.49-1.10) for coffee and 1.05 (0.85-1.31) for black tea. Analyses of other metrics did not reveal any clear patterns of increasing or decreasing risk with increasing amounts or duration of consumption. There was no strong evidence of OR modification by sex or smoking level. The OR estimates did not materially differ by histological subtype for either of the beverages. CONCLUSION: Our results do not provide strong support for associations between consumption of coffee and black tea and lung cancer.

Bridging the etiologic and prognostic outlooks in individualized assessment of absolute risk of an illness: application in lung cancer.

Assessment of individual risk of illness is an important activity in preventive medicine. Development of risk-assessment models has heretofore relied predominantly on studies involving follow-up of cohort-type populations, while case-control studies have generally been considered unfit for this purpose. To present a method for individualized assessment of absolute risk of an illness (as illustrated by lung cancer) based on data from a 'non-nested' case-control study. We used data from a case-control study conducted in Montreal, Canada in 1996-2001. Individuals diagnosed with lung cancer (n = 920) and age- and sex-matched lung-cancer-free subjects (n = 1288) completed questionnaires documenting life-time cigarette-smoking history and occupational, medical, and family history. Unweighted and weighted logistic models were fitted. Model overfitting was assessed using bootstrap-based cross-validation and 'shrinkage.' The discriminating ability was assessed by the c-statistic, and the risk-stratifying performance was assessed by examination of the variability in risk estimates over hypothetical risk-profiles. In the logistic models, the logarithm of incidence-density of lung cancer was expressed as a function of age, sex, cigarette-smoking history, history of respiratory conditions and exposure to occupational carcinogens, and family history of lung cancer. The models entailed a minimal degree of overfitting ('shrinkage' factor: 0.97 for both unweighted and weighted models) and moderately high discriminating ability (c-statistic: 0.82 for the unweighted model and 0.66 for the weighted model). The method's risk-stratifying performance was quite high. The presented method allows for individualized assessment of risk of lung cancer and can be used for development of risk-assessment models for other illnesses.

Sex differences in health behavior change after premature acute coronary syndrome.

BACKGROUND: Limited information is available on the health behavior profile of patients with premature acute coronary syndrome (ACS). The purpose of this study is to desribe the health bahvior of young patients with ACS at the baseline and 1 year post-ACS and examine sex differences. METHODS: GENESIS-PRAXY is a prospective cohort study of adults (18-55 years old) hospitalized with ACS from 26 centers located in Canada, United States, and Switzerland. Data on diet, physical activity, smoking, alcohol consumption, and recreational drug use were collected through self-administered questionnaires at baseline and 1 year post-ACS. RESULTS: Our analysis included 740 patients with complete data. At baseline, the health behavior profile of young patients with ACS was worse than that of the general population. Men had a lower fruit and vegetable intake, consumed alcohol more, and used recreational drugs more than women. Conversely, fewer men than women were smokers (34% vs 42%). At 1 year post-ACS, the proportion of those consuming ≥5 daily servings of fruits and vegetables increased modestly (+5% vs +1%, for men vs women) but remained lower than the general population. Among women, the prevalence of smoking remained about twice as high as the general population. Recreational drug use also remained higher than in the general population. CONCLUSIONS: Despite small improvements at 1 year post-ACS, the health behavior profile of young patients remained worse than that of the general population. Greater efforts to improve health behaviors post-ACS among young patients are needed, and a sex-based approach may be required to ensure successful behavioral changes.

Cigarette smoking may modify the association between cannabis use and adiposity in males.

INTRODUCTION: The few population-based studies that investigate the association between cannabis use and adiposity are inconclusive possibly because nicotine moderates the effect of cannabis on adiposity. The objective was to test the hypotheses that the association between cannabis use and adiposity in young men and women is modified by cigarette smoking. METHODS: Data were drawn from the Nicotine Dependence in Teens (NDIT) study, a 13-year prospective cohort investigation of the natural course of nicotine dependence. A total of 271 males and 319 females aged 12-13years at cohort inception provided data on past-year cannabis use and number of cigarettes smoked per day in the past three months, at age 20years. Outcomes included change in body mass index (BMI) and in waist circumference (WC) from ages 17 to 24years. The hypothesis was tested in multiple linear regression models that included interaction terms for cannabis use and cigarette smoking and controlled for physical activity, sedentary behavior, alcohol use, and level of the outcome at baseline. RESULTS: The association between cannabis use and change in adiposity was U-shaped in male non-smokers and in females, and an inverted U-shape in male smokers. In males, the interaction between cannabis use and cigarette smoking was significant in both the models for change in BMI (p=0.004; n=271) and change in WC (p=0.04; n=250). In females, the interaction between cannabis use and cigarette smoking was not significant. CONCLUSION: Smoking cigarettes appears to modify the association between cannabis use and adiposity in young men.

Cohort Profile: The Nicotine Dependence in Teens (NDIT) Study.

The Nicotine Dependence in Teens (NDIT) study is a prospective cohort investigation of 1294 students recruited in 1999-2000 from all grade 7 classes in a convenience sample of 10 high schools in Montreal, Canada. Its primary objectives were to study the natural course and determinants of cigarette smoking and nicotine dependence in novice smokers. The main source of data was self-report questionnaires administered in class at school every 3 months from grade 7 to grade 11 (1999-2005), for a total of 20 survey cycles during high school education. Questionnaires were also completed after graduation from high school in 2007-08 and 2011-12 (survey cycles 21 and 22, respectively) when participants were aged 20 and 24 years on average, respectively. In addition to its primary objectives, NDIT has embedded studies on obesity, blood pressure, physical activity, team sports, sedentary behaviour, diet, genetics, alcohol use, use of illicit drugs, second-hand smoke, gambling, sleep and mental health. Results to date are described in 58 publications, 20 manuscripts in preparation, 13 MSc and PhD theses and 111 conference presentations. Access to NDIT data is open to university-appointed or affiliated investigators and to masters, doctoral and postdoctoral students, through their primary supervisor (www.nditstudy.ca).

Genetic variants and early cigarette smoking and nicotine dependence phenotypes in adolescents.

BACKGROUND: While the heritability of cigarette smoking and nicotine dependence (ND) is well-documented, the contribution of specific genetic variants to specific phenotypes has not been closely examined. The objectives of this study were to test the associations between 321 tagging single-nucleotide polymorphisms (SNPs) that capture common genetic variation in 24 genes, and early smoking and ND phenotypes in novice adolescent smokers, and to assess if genetic predictors differ across these phenotypes. METHODS: In a prospective study of 1294 adolescents aged 12-13 years recruited from ten Montreal-area secondary schools, 544 participants who had smoked at least once during the 7-8 year follow-up provided DNA. 321 single-nucleotide polymorphisms (SNPs) in 24 candidate genes were tested for an association with number of cigarettes smoked in the past 3 months, and with five ND phenotypes (a modified version of the Fagerstrom Tolerance Questionnaire, the ICD-10 and three clusters of ND symptoms representing withdrawal symptoms, use of nicotine for self-medication, and a general ND/craving symptom indicator). RESULTS: The pattern of SNP-gene associations differed across phenotypes. Sixteen SNPs in seven genes (ANKK1, CHRNA7, DDC, DRD2, COMT, OPRM1, SLC6A3 (also known as DAT1)) were associated with at least one phenotype with a p-value <0.01 using linear mixed models. After permutation and FDR adjustment, none of the associations remained statistically significant, although the p-values for the association between rs557748 in OPRM1 and the ND/craving and self-medication phenotypes were both 0.076. CONCLUSIONS: Because the genetic predictors differ, specific cigarette smoking and ND phenotypes should be distinguished in genetic studies in adolescents. Fifteen of the 16 top-ranked SNPs identified in this study were from loci involved in dopaminergic pathways (ANKK1/DRD2, DDC, COMT, OPRM1, and SLC6A3). IMPACT: Dopaminergic pathways may be salient during early smoking and the development of ND.

Estimating the proportion of cases of lung cancer legally attributable to smoking: a novel approach for class actions against the tobacco industry.

OBJECTIVES: The plaintiffs' lawyers for a class action suit, which was launched in Quebec on behalf of all patients with lung cancer whose disease was caused by cigarette smoking, asked us to estimate what proportion of lung cancer cases in Quebec, if they hypothetically could be individually evaluated, would satisfy the criterion that it is "more likely than not" that smoking caused the disease. METHODS: The novel methodology we developed is based on the dose-response relationship between smoking and lung cancer, for which we use the pack-years as a measure of smoking, and the distribution of pack-years of smoking among cases. RESULTS: We estimated that the amount of smoking required to satisfy the "more likely than not" criterion is between 3 and 11 pack-years. More than 90% of the Quebec cases satisfied even the most conservative of these thresholds. CONCLUSIONS: More than 90% of cases of lung cancer in Quebec are legally attributable to smoking. The methodology enhances the ability to conduct class action suits against the tobacco industry.

Predictors of the occurrence of smoking discontinuation in novice adolescent smokers.

BACKGROUND: While long-term cessation is an outcome of interest in adult smokers, little is known about discontinuing smoking in adolescent smokers. The objective was to identify the predictors of the occurrence of smoking discontinuation in novice smokers. METHODS: Data were available for 620 adolescent smokers participating in a longitudinal study on the natural course of nicotine dependence. Data on smoking discontinuation (i.e., stopping smoking for ≥12 consecutive months) were collected in 20 cycles over five years from grade 7 to 11 (1999-2005). Data on 37 potential predictors representing a wide range of demographic, psychosocial, health, lifestyle, smoking-related, and context-related characteristics were collected once, 2 to 3 times, or 20 times. Pooled logistic regression was used to test the association between each potential predictor and smoking discontinuation, adjusting for potential confounders. RESULTS: Forty percent of 620 participants discontinued smoking during follow up. Male sex [OR (95% confidence interval), 1.8 (1.3-2.4)], age [1.3 (1.1-1.5)], cigarette package warnings [0.6 (0.5-0.9)], team sports participation [1.4 (1.1-1.9)], family stress [0.7 (0.6-1.0)], worrying about weight [0.6 (0.5-0.9)], overweight [0.7 (0.5-1.0)], illicit drugs use [0.5 (0.4-0.7)], tolerance [0.6 (0.4-1.0)], and other nicotine dependence symptoms [1.0 (0.9-1.0)] were statistically significantly associated with smoking discontinuation. CONCLUSIONS: Both individual and context-level factors were associated with smoking discontinuation. IMPACT: Programs and policy targeting novice adolescent smokers may be more effective if factors associated with long-term smoking discontinuation are taken into consideration. In particular, young smokers may need help with dependence symptoms, body weight issues, family functioning, and polysubstance use. Cigarette package warnings may be effective in helping adolescents discontinue smoking. Cancer Epidemiol Biomarkers Prev; 23(6); 1090-101. ©2014 AACR.

Sex- and gender-related risk factor burden in patients with premature acute coronary syndrome.

BACKGROUND: Few contemporary data exist on traditional (TRF) and non-TRF (NTRF) burden in patients with premature acute coronary syndrome (ACS). METHODS: Prevalence of TRFs and NTRFs were measured in 1015 young (55 years old or younger) ACS patients recruited from 26 centres in Canada, the United States, and Switzerland. Risk factors were compared across sex and family history categories, and against a sample of the general Canadian population based on the 2000-2001 Canadian Community Health Survey. The 10- and 30-year risks of cardiovascular disease (CVD) were estimated using Framingham Risk Scores. RESULTS: Risk factors were more prevalent in premature ACS patients compared with the general population. Young women with a family history of coronary artery disease showed the greatest risk factor burden including TRFs of hypertension (67%), dyslipidemia (67%), obesity (53%), smoking (42%), and diabetes (33%), and NTRFs of anxiety (55%), low household income (44%), and depression (37%). The estimated median 10-year risk of CVD was 7% (interquartile range [IQR], 3%-9%) in women and 13% (IQR, 7%-17%) in men, whereas the 30-year risk of CVD was 36% (IQR, 22%-49%) in women and 44% (IQR, 31%-57%) in men. CONCLUSIONS: Patients with premature ACS, especially women with a positive family history, are characterized by a very high risk factor burden that is poorly captured by 10-year risk estimates but better captured by 30-year estimates. Consideration of NTRFs and use of 30-year risk estimates might better estimate risk in young individuals and improve the prevention of premature ACS.

Effects of antiperspirant aluminum percent composition and mode of application on mock microcalcifications in mammography.

OBJECTIVE: Active ingredients in antiperspirants - namely, aluminum-based complexes - can produce radiopaque particles on mammography, mimicking microcalcifications. The present study was designed to investigate whether the appearance of antiperspirant induced radiopaque particles observed on mammograms is dependent on the percentage of aluminum-based complexes in antiperspirants and/or on their mode of application. METHODS: A total of 43 antiperspirants with aluminum-based complex percentages ranging between 16% and 25% were tested. Each antiperspirant was applied to a single use plastic shield and then placed on an ultrasound gel pad, simulating breast tissue. Two experiments were performed, comparing antiperspirants based on (1) their percentage of aluminum-based complexes (20 antiperspirants) and (2) their mode of applications (solid, gel, and roll-on) (26 antiperspirants). Two experienced, blinded radiologists read images produced in consensus and assessed the appearance of radiopaque particles based on their density and shape. RESULTS: In experiment 1, there was no statistically significant association between the percent aluminum composition of invisible solid antiperspirants and the density or shape of the radiopaque particles (p-values>0.05). In experiment 2, there was a statistically significant association between the shape of the radiopaque particles and the mode of application of the antiperspirant (p-value=0.0015). CONCLUSIONS: Our study suggests that the mammographic appearance of the radiopaque antiperspirant particles is not related to their percent composition of aluminum complexes. However, their mode of application appears to influence the shape of radiopaque particles, solid antiperspirants mimicking microcalcifications the most and roll-on antiperspirants the least.

Incidence and determinants of cigarette smoking initiation in young adults.

PURPOSE: To describe the incidence and identify predictors of smoking initiation in young adults. METHODS: Data were collected in self-report questionnaires in 22 cycles over 13 years in a prospective cohort investigation of 1,293 students recruited in 1999-2000 from all grade 7 classes in a convenience sample of 10 high schools in Montreal, Canada. Participants were 12.7 years of age on average at cohort inception and 24.0 years of age in cycle 22. Independent predictors of smoking initiation in young adulthood (post-high school) were identified in multivariable logistic regression analysis using generalized estimating equations. RESULTS: Of 1,293 participants, 75% initiated smoking by cycle 22. Of these, 44%, 43%, and 14% initiated before high school, during high school, and in the 6 years after high school, respectively. The incidence density rate of initiation was .33, .13, .14, .11, and .12 initiation events per person-year in grade 7, 8, 9, 10, and 11, respectively, and .05 post-high school. Independent predictors of smoking initiation in young adults included alcohol use, higher impulsivity, and poor academic performance. CONCLUSIONS: A total of 14% of smokers who initiated smoking before age 24 years did so after high school. The predictors of initiation in young adults may provide direction for relevant preventive interventions.