Adriana Lori

Objective To compare use of electronic nicotine delivery systems (ENDS) with nicotine replacement therapies (NRTs) on risk of cigarette smoking relapse by people who had already quit cigarettes. Design Prospective cohort study. Setting The American Cancer Society Cancer Prevention Study-3, a nationwide US cohort with follow-up every 3 years beginning in 2015. Participants Adults who in 2015 had already quit smoking (n=3112) or were smoking (n=1018) and who in 2018 reported past or current exclusive use of ENDS or NRT and provided smoking status. Outcome measures Relapse to cigarette smoking in 2018 among people who were already quit in 2015, and abstinence from cigarettes in 2018 among people who were smoking in 2015. Results Among respondents who had already quit in 2015, the unadjusted risk of relapse in 2018 was approximately three times greater for those who reported past exclusive ENDS versus past exclusive NRT use (11.2% vs 3.9%; relative risk (RR)=2.90, 95% CI 2.12 to 3.98). This association remained significant in a multivariable-adjusted model (RR=2.09, 95% CI 1.49 to 2.92). Among those smoking in 2015, the unadjusted likelihood of abstinence in 2018 was higher for those who reported current ENDS versus NRT use (RR=1.35, 95% CI 1.01 to 1.80), but the multivariable model adjusted for smoking frequency indicated no difference in abstinence (RR=1.38; 95% CI 0.93 to 2.05). Conclusions ENDS use was associated with greater relapse risk than NRT among people who had already quit. Although ENDS may support shorter-term cessation, further long-term observational research is needed to clarify relapse risks associated with ENDS relative to NRT.

Characteristics of 12 case-control datasets from the ENIGMA consortium partners.

Detail description of the functional categorization of analyzed CHEK2 missense variants.

Frequencies of all reported germline CHEK2 variant carriers and carriers of variants concordantly categorized by functional our kinase assays in breast cancer patients and controls in 12 analyzed population datasets.

List of all analyzed CHEK2 variants with results of KAP1/CHK2 kinase and localization assays and the results from recent previously published functional analyses of the CHEK2 VUS.

Osteosarcoma, the most common childhood bone tumor, can occur in rare cancer predisposition syndromes; however, most are sporadic with no known predisposing factors. We investigated the frequency of SMARCAL1 putative pathogenic variants in our large ongoing study of 2119 osteosarcoma patients, their relation to patient characteristics, and the population prevalence. Our analysis uncovered a higher frequency of SMARCAL1 pathogenic variants across 3 osteosarcoma patient sets (1.8%, n = 2119) than in 2625 comparably sequenced cancer-free individuals (0.3%; P < .001). Patients with SMARCAL1 pathogenic variants had statistically significantly improved overall survival compared with patients without these variants (hazard ratio [HR] = 0.36, 95% confidence interval [CI] = 0.14 to 0.96; P = .034). In the UK Biobank (469 557 exomes), there was a 33-fold increased risk of osteosarcoma in individuals with SMARCAL1 pathogenic variants. These results identify SMARCAL1 as a new osteosarcoma predisposition gene and thus warrant follow-up to identify the mechanisms by which SMARCAL1 contributes to the etiology of osteosarcoma.

Supplementary Figure S1 shows predicted lifetime risks of breast cancer based on carrier status and PRS, without and with ERS

Supplementary Table S5 shows discrimination of models with different combinations of risk factors with controls and invasive breast cancer cases

Supplementary Table S4 shows discrimination and fit of models with different combinations of risk factors with controls and all breast cancer cases

Supplementary Table S2 shows breast cancer risk factors and relative risks in the iCARE-Lit breast cancer risk prediction model