Skin represents the largest barrier of the human body to external insults. Histologically, skin is divided into three distinct layers, namely, epidermis, dermis, and hypodermis [1] (Figure 1). In general, skin provides protection from external pressures, serves as a source of percutaneous absorption, and has a significant role in thermoregulation. It is also responsible for the synthesis of macromolecules and aesthetics. The hypodermis consists of subcutaneous fatty tissue along with connective tissue. The dermis exhibits vascularity, neuronal ending, receptors (touch, nociception, and proprioception), hair, and glands. The extracellular matrix of the dermis contains connective tissue rich in collagen and elastin. The epidermis is the outer skin layer which is in direct contact with the atmosphere [1,2]. Approximately 80% of epidermal cells are keratinocytes. Due to its contact with the external environment, these cells undergo continuous wear and tear with constant replacement by newer keratinocytes from the basal epidermal layer. The separation between the epidermis and dermis is through the basement membrane [3]. Other specialized cells in the epidermis include melanocytes (melanin producing), Merkel cells (sensory), and Langerhans cells (immune role). All the cells of the skin perform complex functions, working to achieve and maintain constant homeostasis against various internal and external stimuli. In the case of damage to the skin cells, connective tissue, and other macromolecules, normal processes are dysregulated and give rise to various diseases, including mycoses, inflammatory diseases, and neoplasms [1,4,5].

Neoplastic development and progression in the skin is a process consisting of three phases: initiation, followed by promotion and progression of tumor cells (Figure 2). The etiology of initiation may be either exogenous (chemicals, virus, ultraviolet (UV) radiation) or endogenous factors (inflammation). Damage caused by these factors to skin cells is irreparable when cells that cannot regain normal function advance to neoplastic progression [6]. Most ultraviolet B (UVB) radiation induces DNA damage that occurs as a transition from C to T or CC to TT in various genes including tumor suppressor gene p53 [7]. Ultraviolet A (UVA) radiation causes mutations via 8-oxodG. These are present as transitions from AT to CG in various genes that regulate cell cycle, apoptosis, and genomic stability (p53) [7,8]. Genetic mutation and continuous exposure to UV radiation leads to the advancement of initiated cells into the promotion stage [9]. Cells in the initiation stage replicate more vigorously and have less of a tendency to undergo apoptosis [9]. Actinic keratosis (AK) is an example of a precancerous lesion in humans that exhibits extensive mutations when compared with normal human skin cells [10].

Basal cell carcinoma (BCC), as well as squamous cell carcinoma (SCC), constitute the majority of non-melanoma skin cancers (NMSCs), with Caucasians being affected the most. Both arise from the cancerous transformation of normal keratinocytes [4,8]. Rogers et al. have estimated that approximately two million procedures in about 1.3 million individuals were carried out in 2012, and has increased in recent years [11]. Individuals usually develop invasive NMSCs in later stages of life due to its long latent period, even if the tumor-initiating mutations occurred during childhood. The incidence is less common at a younger age [11,12] and it is more frequent in men [13]. As the fifth most expensive cancer, NMSCs account for the expenditure of billions of dollars in health care and treatment [14]. Usually, patients diagnosed with NMSC die from secondary tumors in the lungs, prostate, or colon resulting from distant metastasis [15]. Therefore, early diagnosis and prompt treatment is highly recommended.

In the United States, most of the reported cases of BCC account for >3 million patients annually [11,12]. BCCs exhibit a slower growth rate with a rare chance of metastasis [16], though it does have a tendency to invade surrounding tissues [17]. In the US, SCC remains the second most prevalent skin cancer, accounting for 0.2–0.4 million cases each year. SCC has more of a tendency to metastasize, exhibiting a rate of approximately 4%. The annual number of deaths from metastatic disease is approximately 3000 [15,18,19]. The mortality rate increases in certain cases such as that of immunocompromised individuals [20]. Several studies have explored the transformation mechanism from normal keratinocytes to AK and finally, to SCC. It is believed that a greater period of latency occurs in SCC because AK is resistant to increases in harmful mutations that lead to SCC [10].

The current treatment for NMSCs includes complete eradication of the lesion while preserving the structural and functional architecture of the skin. Current treatment modalities involve surgical intervention including excision, curettage and electrodessication, cryosurgery, micrographic surgery, radiotherapy, and photodynamic therapy. Surgical procedures, such as the Mohs procedure, are preferred to other methods in cases of low-risk lesions [21]. However, the chance of recurrence is high with surgical procedures lacking a complete histological evaluation of the tumor to ensure its entire excision [22].

3. Role of Whole Fruits and Vegetables in Skin Cancer Prevention