The most important questions in cancer research and clinical oncology Question 2-5.Obesity-related cancers:more questions than answers

Obesity is recognized as the second highest risk factor for cancer. The pathogenic mechanisms underlying tobaccorelated cancers are well characterized and efective programs have led to a decline in smoking and related cancers, but there is a global epidemic of obesity without a clear understanding of how obesity causes cancer. Obesity is heterogeneous, and approximately 25% of obese individuals remain healthy(metabolically healthy obese, MHO), so which fat deposition(subcutaneous versus visceral, adipose versus ectopic) is "malignant"? What is the mechanism of carcinogenesis? Is it by metabolic dysregulation or chronic inflammation? Through which chemokines/genes/signaling pathways does adipose tissue influence carcinogenesis? Can selective inhibition of these pathways uncouple obesity from cancers? Do all obesity related cancers(ORCs) share a molecular signature? Are there common(overlapping) genetic loci that make individuals susceptible to obesity, metabolic syndrome, and cancers? Can we identify precursor lesions of ORCs and will early intervention of high risk individuals alter the natural history? It appears unlikely that the obesity epidemic will be controlled anytime soon; answers to these questions will help to reduce the adverse efect of obesity on human condition.

The most important questions in cancer research and clinical oncology

Specific research foci:(1) Mouse models of gamma-herpes virus-68(γHV-68) and polyomavirus(Py V) infections during neonatal versus adult life.(2) For human papilloma virus(HPV)-positive oropharyngeal carcinoma(OPC)—(a) Asking the question: Is oral sex a powerful carcinogen?(b) Examining the evidence for the vertical transmission of HPV infection.(c) Examining the relationship between HPV and Epstein–Barr virus(EBV) infections and nasopharyngeal cancer(NPC) in West European, East European, and East Asian countries.(d) Examining the association between HPVpositive OPC and human leukocyte antigen(HLA).(3) For non-smoking East Asian female lung adenocarcinoma—(a) Examining the incidence trends of HPV-positive OPC and female lung adenocarcinoma according to birth cohorts.(b) Examining the association between female lung adenocarcinoma and HPV.(c) Examining the associations of lung adenocarcinoma with immune modulating factors.(4) For triple-negative breast carcinoma(TNBC) in East Asians—(a) Examining the association between TNBC and HPV.(b) Examining the unique epidemiological characteristics of patients with TNBC. A summary "epidemiological" model tying some of these findings together.