ABSTRACT
The prevalence of obesity has seen a significant rise over recent years, making it a global health concern. This surge has been linked to a higher risk of several metabolic disorders and cancers. This article aims to review the latest evidence highlighting the connection between an increased Body Mass Index (BMI) and the incidence of cancer, focusing on the critical biological mechanisms and pathways, such as the interplay of adipokines, cytokines, and growth factors. Additionally, it offers insights into obesity’s impact on cell proliferation and metastasis. The article underscores the necessity of a comprehensive strategy to combat the obesity epidemic, which includes lifestyle changes and routine cancer screenings, to improve life quality.
INTRODUCTION
Obesity causes a shift in the body’s metabolic state from normal to abnormal, a key contributor to various metabolic syndromes (Bitzur et al., 2016). The fat stored in the body serves not only as an energy source but also aids in the secretion of various hormones, which can cause harmful metabolic effects ranging from insulin resistance to chronic metabolic syndromes. Past understanding suggested obesity’s implications were limited to hyperinsulinemia, hyperglycemia, hypertension, and cardiovascular diseases. However, recent research has revealed the presence of specific molecular mechanisms related to adipose tissues in obese individuals that can lead to different types of cancers (Nimptsch, Pischon, & investigation, 2015).
THE ROLE OF OBESITY IN VARIOUS CANCERS
There is a growing consensus in the scientific community that obesity significantly contributes to the pathophysiology of diverse cancers, including liver, prostate, breast, and colorectal cancer (Saitta, Pollicino, & Raimondo, 2019; N. Tzenios, M. E. Tazanios, & M. J. M. Chahine, 2022b; Kang, LeRoith, & Gallagher, 2018; Dai, Xu, & Niu, 2007).
THE IMPACT OF OBESITY ON LIVER CANCER
Non-alcoholic fatty liver disease (NAFLD), a critical liver health concern in the 21st century, is predominantly caused by the rising prevalence of obesity. NAFLD is characterized by an excessive accumulation of triglycerides (≥ 5% TGs) in liver tissues, independent of excessive alcohol intake or other liver diseases such as chronic hepatitis B or C. The disease may progress to a severe stage known as Non-alcoholic steatohepatitis (NASH) (Chalasani et al., 2018). NAFLD is considered a hepatic manifestation of metabolic syndrome, associated with various metabolic comorbidities such as Type 2 diabetes mellitus (T2DM), hyperlipidemia, and arterial hypertension, in addition to obesity (Cholongitas et al., 2021). In terms of epidemiology, NAFLD affects about a quarter of the world’s population, a figure expected to rise to 56% within the next decade. NAFLD is also seen as a significant cause of hepatocellular carcinoma (HCC) (de Hoon, Eichenberger, & Vitkup, 2010).
THE IMPACT OF OBESITY ON PROSTATE CANCER
Obesity is a substantial public health concern, affecting over 30% of individuals in the United States, driven by various external (environmental) and internal (psychological, neuroendocrine, and genetic) factors (Tzenios, Tazanios, et al., 2022a). Globally, prostate cancer is the second most prevalent cancer type and the second leading cause of cancer-related death in men (Jemal et al., 2011). The connection between a higher BMI and the pathophysiology of prostate cancer remains somewhat unclear; however, numerous studies have identified a significant association between obesity and prostate cancer prognosis (Guerrios-Rivera et al., 2017). Research has shown that obesity in early life stages negatively impacts the prognosis of prostate cancer (Möller et al., 2016). Further studies indicated that a higher BMI is associated with an increased mortality rate due to prostate cancer (Taghizadeh et al., 2015). Analysis from the Prostate Cancer Prevention Trial (PCPT) demonstrated that obesity increases the risk of high-grade prostate cancer (Gong et al., 2006). Consequently, the progression of cancer mediated by obesity is a significant concern. Obesity is linked to lower disease-free survival rates and overall survival across all subtypes of breast cancer (Lohmann et al., 2021).
THE IMPACT OF OBESITY ON BREAST CANCER
Breast cancer is the most commonly diagnosed cancer in women, and according to the Global Cancer Statistics 2020, its prevalence has overtaken that of lung cancer globally (Sung et al., 2021). An elevated BMI, a key factor in the pathophysiology of postmenopausal breast cancer, can be mitigated by adopting a healthier and more active lifestyle (Clinton, Giovannucci, & Hursting, 2020).
For premenopausal women, ovaries are the primary source of estrogen. Post-menopause, however, adipose tissue becomes the main site for estrogen production. Consequently, obese women possess higher postmenopausal estrogen levels, making them more susceptible to estrogen’s pro-tumorigenic effects (Bhardwaj et al., 2019).
The scientific evidence linking obesity and breast cancer is complex and varies by subtype and menopausal status. Obesity in postmenopausal women increases the overall relative risk of developing breast cancer to 1.33, primarily due to higher incidences of estrogen receptor (ER)+ breast cancers. Obesity is also associated with the onset and progression of postmenopausal triple-negative breast cancer (TNBC).
Genetic markers of a higher BMI, such as various single nucleotide polymorphisms linked to fasting glucose and insulin, correlate with breast cancer risk, independent of familial background, age, or menopausal status. This underscores the importance of the relationship between obesity, breast cancer risk, and genetics (Devericks, Carson, McCullough, Coleman, & Hursting, 2022).
Obesity is also associated with metabolic changes and a chronic inflammatory state, evidenced by an increase in inflammatory cells and markers (Shoelson, Herrero, & Naaz, 2007). Obesity directly impacts the progression of breast cancer due to the higher BMI and the corresponding increase in peripheral estrogen production in adipose tissues.
Patients with high BMI exhibit reduced concentrations of sex hormone-binding globulin, which may contribute to poorer breast cancer prognosis. A significant increase in estrogen production and aromatase activity is associated with uncontrolled breast cancer cell growth (Shoelson et al., 2007). However, it remains unclear whether the heightened levels of insulin, insulin growth factor, and sex hormones typically found in overweight breast cancer patients could cause substantial mitogenic activity (Stephenson, Rose, & cancer, 2003).
THE CONNECTION BETWEEN OBESITY AND COLORECTAL CANCER
Colorectal cancer (CRC) stands as the third most common cancer type and the third leading cause of cancer-related mortality among both genders in the United States. The steady rise in CRC cases seen in recent epidemiological studies highlights an ongoing need to explore factors that could contribute to this increase. One of the risk factors showing a consistent and progressive growth in the contemporary world is obesity. Obesity, a multifaceted condition characterized by numerous metabolic and physiological alterations, is known to foster carcinogenesis. The gut microbiome, which undergoes modifications in obesity, has also been implicated in CRC (Goldbaum, 2022). A higher Body Mass Index (BMI) is the fifth leading cause of adult mortality, responsible for at least 2.8 million deaths annually. In Europe, overweight and obesity have been associated with 11% of CRC incidences. Moreover, some research projects that higher BMI can increase the risk of colorectal cancer by 30-70% in men, a pattern less evident in women (Bardou, Barkun, & Martel, 2013). Even though visceral and subcutaneous areas serve as the primary storage for excess fat, a recent study reported a higher prevalence of abdominal obesity (27.8% in men and 45.9% in women) (Abajo et al., 2012). Metabolic Syndrome (MS) only impacts about two-thirds of obese individuals, while some maintain normal metabolism. MS plays a key role in linking obesity to most of its complications, including diabetes, cardiovascular disease, and an increased risk of cancer, although this association may vary across different ethnicities (Wildman et al., 2008). In conclusion, a handful of studies suggest that weight loss might reduce the risk of cancer development (Tzenios, Tazanios, Poh, & Chahine, 2022), specifically colorectal cancer. Weight loss, achieved through a healthy diet or potentially with bariatric surgery, can disrupt the interplay between gut microbiota and host metabolic and physiological functions, which in turn decreases the prevalence of metabolic syndrome and maintains appropriate levels of growth factors, inflammatory cytokines, and adipokines.
CONCLUSION
Obesity represents a considerable public health concern, impacting a substantial percentage of the global population. As illustrated above, its impact is not only restricted to direct health outcomes such as cardiovascular disease and diabetes, but it also plays a significant role in the incidence and prognosis of several types of cancer, including prostate, breast, and colorectal cancer.
There is an increasing body of evidence suggesting that obesity fosters an environment conducive to carcinogenesis, through a variety of mechanisms, including hormonal imbalances, chronic inflammation, and disruptions to the gut microbiome. These alterations can potentially lead to the development and progression of cancer. Despite some variations observed in different populations and across genders, obesity has been generally linked with an elevated risk of these cancers, underlining the urgency of effective interventions targeting obesity.
Moreover, the interplay between obesity and cancer is complex and multi-dimensional. Therefore, further research is crucial to elucidate the underlying molecular mechanisms and pathways. This knowledge can guide the development of targeted prevention strategies and novel therapeutics. The emerging evidence pointing towards the beneficial effects of weight loss on cancer risk also warrants more attention. Comprehensive weight management strategies, including a balanced diet, regular exercise, and potentially bariatric surgery, can be critical in mitigating cancer risk in obese individuals.
In conclusion, addressing obesity is not only a strategy to combat a widespread health issue but is also a potential pathway to reducing the global burden of cancer. Public health efforts should continue to emphasize healthy lifestyle choices, early intervention in individuals with obesity, and further research into the mechanistic links between obesity and cancer.
Resource: http://eprajournals.net/index.php/IJRD/article/view/1503/1514
