Molecular landscape of esophageal cancer: implications for early detection and personalized therapy

Esophageal cancer (EC) is one of the most lethal cancers and a public health concern worldwide, owing to late diagnosis and lack of efficient treatment. Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are main histopathological subtypes of EC that show striking differences in geographical distribution, possibly due to differences in exposure to risk factors and lifestyles. ESCC and EAC are distinct diseases in terms of cell of origin, epidemiology, and molecular architecture of tumor cells. Past efforts aimed at translating potential molecular candidates into clinical practice proved to be challenging, underscoring the need for identifying novel candidates for early diagnosis and therapy of EC. Several major international efforts have brought about important advances in identifying molecular landscapes of ESCC and EAC toward understanding molecular mechanisms and critical molecular events driving the progression and pathological features of the disease. In our review, we summarize recent advances in the areas of genomics and epigenomics of ESCC and EAC, their mutational signatures and immunotherapy. We also discuss implications of recent advances in characterizing the genome and epigenome of EC for the discovery of diagnostic/prognostic biomarkers and development of new targets for personalized treatment and prevention

Global burden of disease due to smokeless tobacco consumption in adults : analysis of data from 113 countries

BACKGROUND: Smokeless tobacco is consumed in most countries in the world. In view of its widespread use and increasing awareness of the associated risks, there is a need for a detailed assessment of its impact on health. We present the first global estimates of the burden of disease due to consumption of smokeless tobacco by adults. METHODS: The burden attributable to smokeless tobacco use in adults was estimated as a proportion of the disability-adjusted life-years (DALYs) lost and deaths reported in the 2010 Global Burden of Disease study. We used the comparative risk assessment method, which evaluates changes in population health that result from modifying a population's exposure to a risk factor. Population exposure was extrapolated from country-specific prevalence of smokeless tobacco consumption, and changes in population health were estimated using disease-specific risk estimates (relative risks/odds ratios) associated with it. Country-specific prevalence estimates were obtained through systematically searching for all relevant studies. Disease-specific risks were estimated by conducting systematic reviews and meta-analyses based on epidemiological studies. RESULTS: We found adult smokeless tobacco consumption figures for 115 countries and estimated burden of disease figures for 113 of these countries. Our estimates indicate that in 2010, smokeless tobacco use led to 1.7 million DALYs lost and 62,283 deaths due to cancers of mouth, pharynx and oesophagus and, based on data from the benchmark 52 country INTERHEART study, 4.7 million DALYs lost and 204,309 deaths from ischaemic heart disease. Over 85 % of this burden was in South-East Asia. CONCLUSIONS: Smokeless tobacco results in considerable, potentially preventable, global morbidity and mortality from cancer; estimates in relation to ischaemic heart disease need to be interpreted with more caution, but nonetheless suggest that the likely burden of disease is also substantial. The World Health Organization needs to consider incorporating regulation of smokeless tobacco into its Framework Convention for Tobacco Control