Colorectal cancer (CRC) is the fourth most commonly diagnosed gastrointestinal (GI) malignancy and the third leading cause of cancer-related death worldwide [1–3]. It occurs in 5% of the general population at any given time [1]. According to GLOBOCAN 2018, it is the third common cancer in Iran with 9864 new cases in 2018 [4]. The mean direct medical cost of CRC per patient in Iran is more than 16,000 US dollars [5] and thus,it is estimated that its economic burden will range from 175,000,000 to 250,000,000 US dollars in 2019.
The incidence rate of CRC has increased in both developing and Western countries over the last decades [6–8]. The global burden of CRC is expected to increase by 60% to more than 2.2 million new cases and 1.1 million deaths by 2030 [9]. Each year, over 132.000 new cases of CRC are diagnosed in the United States, and approximately fifty thousand patients will pass away from this cancer [10]. The five-year survival rate is above 90% for first stage of the disease [11]. A large number of evidence has revealed that environmental and modifiable factors such as smoking, alcohol, obesity, unhealthful dietary habits, diabetes and physical inactivity have a major impact on the development of CRC [2, 6, 8, 12, 13]. Based on the diabetes country profiles of the World Health Organization (WHO) in 2016, the prevalence rates of physical inactivity, overweight, and obesity in Iran were 31.9%, 60.5%, and 24.9%, respectively [14]. Generally, unhealthy lifestyles might accounts for up to 70% of CRC etiology [15, 16]. It has been reported that obesity, particularly central obesity is one of the most significant predisposing factors for numerous cancers and chronic diseases [3]. Moreover, it has been shown that obesity is a meaningful contributor to CRC and is considered as a poor prognosis factor in cancer development [11, 17, 18]. On the other hand, losing weight might have desirable effects on the prognosis of the disease [19]. According to the WHO, obesity is defined as a body mass index (BMI): normal weight (BMI: 18.5–24.9 kg/m2), overweight (BMI: 25.0–29.9 kg/m2), obesity (BMI: 30.0–34.9 kg/m2), severe obesity (BMI: 35.0–39.9 kg/m2) and for morbid obesity (BMI ≥40 kg/m2) [1, 2, 20]. Approximately 30% of the American population is classified in the overweight or obese category [21]. Obesity could be associated with obesity-related cancers such as breast, liver, gynaecological, oesophagus, kidney, lung, pancreatic, thyroid, gallbladder and CRC [6, 21]. It initiates different cellular and molecular pathways, which eventually lead to tumor formation. Adipose tissue produces many kinds of hormones and pro-inflammatory cytokines, among them, interleukin 6, tumor necrosing factor-α, leptin and adiponectin provide desirable inflammatory microenvironment conditions for cancerous cells [22, 23]. Current studies have revealed that adipose tissue stimulates proliferation, migration, angiogenesis and oxidative stress induction [21]. In a recent meta-analysis by Dong et al., it was demonstrated that abdominal obesity is highly associated with an increased relative risk of CRC [6].
In addition to obesity, insulin resistance and hyper-insulinaemia, are also associated with CRC [17, 24]. Insulin resistance and insulin response are highly correlated since majority of the insulin-resistant individuals are either in the highest insulin response quartile or the second highest [25]. Besides, numerous epidemiological studies depict that CRC is more prevalent among diabetic patients as compared to non-diabetic ones [26]. Several observations have elucidated that there is an association between diabetes and an elevated incidence ratio of cancer in specific organs such as liver, pancreas, endometrial, breast, bladder, and colon. Aberration in insulin regulation underlies both diabetes and obesity-related tumorigenesis through several signalling pathways such as insulin-like growth factor (IGF)–1 receptors [27, 28].
In the current study, we investigated an association between diagnosis of CRC, obesity and diabetes in the selected group of CRC patients.