Overall weight gain with smoking
Overall, weight gain with smoking cessation may attenuate to the health benefits of smoking cessation for cancer prevention. Substantial evidence from large cohort studies such as Korea National Health Insurance Corporation cohort  and cohort of Swedish men  and meta-analyses of prospective observational studies  suggest a positive association between excess body weight and increased risk of a wide range of cancer types. Although the biological mechanisms by which weight gain accelerates cancer develop may vary by cancer sites, excessive adipose tissue, if accumulated after smoking cessation, may induce insulin resistance, chronic hyperinsulinemia, and localized L-Glutamine that contribute to increased cancer risk [39,40]. Despite these plausible mechanism, further studies are necessary to examine the composite health benefits and harms of smoking cessation in relation to several cancer types.
A notable strength of this study is its large size of study population including more than 1 million young men with reliable information on health examination, medical claims, and death records. Another strength is that we were able to collect data on sociodemographic factors, health status, comorbidities, and family history from a linked database for adjustment in risk estimates for cancer. Also, classification of cancer types in the NHIS database was based on reliable medical claims and relevant codes among the participants , and did not rely on the secondary data source. Furthermore, we were able to conduct several sensitivity analyses with different categorization of weight change that were generally consistent with the main analysis.
Role of the sponsor
Authorship contribution statement
Conflict of interest
Acknowledgement We would like to thank the National Health Insurance Service for providing the dataset (NHIS-2017-1-143). Kyuwoong Kim received a scholarship from the BK21-plus education program provided by the National Research Foundation of Korea. This research was supported by the Ministry of Health and Welfare in the Republic of Korea (Grant No: 20170322652-00).
Introduction Cancer of unknown primary site (CUP) is a high-burden malignancy, with high mortality rates and marginal advances in survival over time [, , ]. The clinical presentation of CUP is highly heterogeneous, ranging from a single metastatic site to disseminated disease. The primary site is classified as unknown after clinically indicated investigations, either exhaustive if the cancer is considered treatable, or limited in advanced disease where ongoing diagnostic investigations is considered unlikely to improve patient survival or quality of life . Indeed, only a minority of CUP cases notified to population-based cancer registries have histological confirmation of metastatic cancer [3,5]. The risk factors for CUP are poorly defined. Older age is a consistently strong risk factor, while male gender, socio-economic deprivation, black race, distance from medical services, and non-migrant populations have been shown to increase risk in one or more studies [3,, , , , ]. In two prospective cohort studies, an increased risk of CUP was observed for smokers [10,11], but no other lifestyle factors. There have been no assessments of the association between a cancer registry notification of CUP and social connectedness. Furthermore, no prior studies have comprehensively adjusted for potential confounders, such as comorbid disease. We sought to identify the independent demographic, social and lifestyle-related risk factors for a cancer registry notification of CUP in a prospective Australian cohort study.
Discussion Our findings confirm the previously reported strong association between a cancer registry notification of CUP and older age [5,6,8,9] and smoking [10,11], and indicate these factors increase risk independent of overall health. As for previous studies, we did not observe an association with body fatness or alcohol consumption [10,11]. Whilst several descriptive studies have pointed to an increased risk of a CUP notification in association with measures of deprivation associated with living in a particular neighbourhood, including low socio-economic position [6,9] and low educational status , this is the first time self-reported educational attainment has been observed to independently predict a cancer registry notification of CUP. Whilst a number of other characteristics related to deprivation were associated with CUP in our cohort, petiole did not remain associated after adjustment. The only previous cohort study to examine self-reported level of education observed no association with risk of CUP, either before or after adjustment for smoking . The reasons for this variation are uncertain, as the categorisation of education levels was similar for the two cohorts. The European Prospective Investigation into Cancer and Nutrition (EPIC) cohort enrolled 35–70 year olds between 1992 and 2000 and, unlike the 45 and Up Study, excluded individuals with a history of cancer at the time of recruitment .