Body fatness as a cause of cancer: epidemiologic clues to biologic mechanisms

Abstract

Carrying excess body fat is a leading cause of cancer. Epidemiologic evidence gives strong clues about the mechanisms that link excess adiposity to risk for several cancer sites. For postmenopausal breast cancer and endometrial cancer, the hyper-estrogenic state that is induced by excess body fatness is the likely cause. For esophageal cancer and gallbladder cancer, chronic local inflammation induced by acid reflux and gallstones is the likely cause, and for liver cancer, local inflammation induced by hepatic fatty infiltration is the likely cause. However, for several other cancers known to be associated with excess adiposity, including cancers of the colon, pancreas, ovary, kidney, and prostate, specific causes are not known. Possible candidates include elevated systemic or local tissue inflammation induced by adiposity and effects of the elevated levels of leptin, insulin, IGFs, and depressed immune function that are seen with excess adiposity. There is growing evidence that intentional weight loss not only reduces circulating levels of cancer-associated factors but that it also reduces cancer incidence and recurrence. Better research is needed to understand the mechanisms that link excess body fat to cancer risk as well as to understand the amount of weight loss needed for substantial cancer risk reduction. Finally, as we develop better understanding of the mediators of the effects of excess body fatness on cancer risk, we should identify pharmacologic interventions that target those mediators so that they can be used to complement weight loss in order to reduce cancer risk.

Identification of Novel SNPs Associated with Risk and Prognosis in Patients with Castration-Resistant Prostate Cancer

“…There is strong evidence that sterol/androgen disposition [1,2], obesity [3,4] and carcinogen activation [5] are related to prostate carcinogenesis and/or disease progression. The liver is central to regulation of each of these processes, and variation in geneencoding enzymes and polypeptides that metabolize and transport endogenous and environ mental carcinogens may explain why some are predisposed to cancer, or a poor prog nosis.…”

Why Are Women with Obesity More Likely to Develop Breast Cancer

“…Breast cancer is classified into two subtypes: ER-positive (+) type and ER-negative (-) type depending on ER abundance within cells [5]. Approximately 70-80% of breast cancers are estrogen-sensitive and clinical evidence shows that ER(+) cancer responds to antiestrogen therapy and has better prognosis, whereas ER(-) cancer is more aggressive and resistant to treatment [15].…”

“…Recently, Park et al investigated the risks of metabolic disorder and obesity phenotypes in breast cancer participants 35-74 years in age [21]. A comprehensive review on application of meta-analysis to BMI and breast cancer was performed [5,6].…”

Adipokines, myokines and cytokines in endometrial cancer patients: relations to obesity phenotype of excessive body mass and features of the tumor

“…В этом плане обращает на себя внимание в частности тот факт, что ожидаемый прирост заболеваемости РЭ и ожире-нием на северо-американском континенте к 2030 г. по отношению к 2005 г. практически совпадает, будучи равным соответственно 59% и 63% [1,4]. К числу фак-торов, опосредующих часто обсуждаемую связь между ожирением и злокачественными новообразованиями, иногда относят некоторые пептиды, выполняющие (несмотря на несомненные терминологические и сущ-ностные перекресты) более общие или более специали-зированные функции и обозначаемые как адипокины, миокины и цитокины [5], причем взаимоотношения по крайней мере части из них (за исключением леп-тина и адипонектина) с опухолевым ростом, включая РЭ, практически не изу чались (как в случае преадипо-цитарного фактора, Pref-1) или изучались (как в слу-чае миостатина), скорее, применительно к кахексии, а не к ожирению. В отношении онкологических про-блем [6,7] весьма редко до настоящего времени учиты-вается также тот факт, что ожирение по своей природе, по крайней мере фенотипически, гетерогенно.…”