## 4 Discussion
On the other hand, there are also studies in the literature showing that ultraviolet B (UVB) radiation can directly induce hBD secretion from keratinocytes [45; 46; 47; 48]. When our study's findings are evaluated together with the literature data, it becomes clear that radiation creates a complex background that can affect oral hBD-1 expression by changing the host-microbial balance and through direct effects on tissues. Considering the anti-tumorigenic effects of hBD-1 [49], there is a need for further studies investigating the radiotherapy-stimulated hBD-1 activation as part of cancer treatment. According to our findings, there were a high number of samples that were under the LOD of the applied analysis protocols (hBD-1 28.7%, hBD-2 28.7%, and hBD-3 76.3%). hBDs are the predominant form of antimicrobial peptides found in periodontal tissues. The quantitative detection of hBDs in oral fluids has been applied in various oral conditions, and the loss of hBD is not routinely encountered [41; 50; 51; 52; 53; 54; 55]. Studies have shown that individuals with periodontitis could have higher levels of hBDs in their saliva compared to individuals without periodontitis [52; 53; 54; 56; 57]. Additionally, research has also shown that there is a positive correlation between the severity of periodontitis in diabetic individuals and hBD levels, meaning that as the severity of periodontitis increases, so do hBD levels [56; 57]. [PERSON] et al. found that patients with periodontitis displayed elevated levels of HBD-2 and hBD-3 in their oral fluids compared to healthy individuals [52; 53]. [PERSON] et al. also reported that mRNA gene expression of hBD-1 is up-regulated in patients with chronic periodontitis [54]. When we evaluate together the literature data and the periodontal condition of our own study group, we are interpreting the values detected below the LOD as being a loss (absence or very low levels of hBD expression). Our study raises the potential that the loss of hBD in oral fluids, including before radiotherapy, may be caused by cancer. There are various studies showing that there is a loss of hBD in oral cancers [18; 29; 30; 40; 58; 59; 60; 61]. It was demonstrated that hBD-1 expression is significantly lower in oral squamous cell carcinoma, a common type of head and neck cancer, compared to healthy gingival tissue [18; 29; 30; 60]. Besides oral cancer, hBD-1 release was found to be significantly down-regulated in epithelial renal cancer, prostate cancers, hepatocellular cancer, lung cancer, cutaneous squamous cell carcinoma, and other cancer types including basal cell of the skin [40; 58; 61; 62; 63; 64]. [PERSON] et al., 2003 concluded that hBD-1 is not expressed in 90% of renal cancer patients and 82% of prostate cancer patients [40]. hBD-1 mRNA is known to be ubiquitously actively secreted in healthy individuals including mucosal tissues [34; 65]. Similar to hBD-1, hBD-2 has also been shown to have lower expression in oral squamous cell carcinoma (OSCC) than in healthy oral cells [30]. [PERSON] et al., 2004 found that hBD-2 concentrations may decrease in patients with tonsillar cancer in the head and neck cancer group when compared to normal tissues in a study on patients with tonsillar cancer in the head and neck cancer group [59]. On the other hand, the expression of hBD-3 in cancer cases is contradictory. Although some studies involving squamous cell oral cancers have shown that hBD-3 is released more than hBD-1 and hBD-2, there are also opposite findings in the literature. [20; 28; 29; 30; 31]. Among the study participants of ours, a significant loss of hBD-3 was found (76.3%) in the pre-radiotherapy stage. It is suggested that human hBD-3 helps to facilitate communication between the gingival epithelium and connective tissue, as well as plays a role in linking innate and acquired immunity [45]. It has been shown that hBD-3 can inhibit the development of periodontitis by suppressingthe inflammatory response in macrophages and reducing cytokine secretion [45; 64; 65].