Pylori Infection and Colon Cancer J Clin Med Res • 2012;4(3):172-176 cancer patients (mean value: 51.6 pg/mL) and the control group (P = n.s.). The analysis showed that there was no statistically sig- nificant difference of the serum gastrin levels in the patients with colorectal malignancy in terms of the location of the pri- mary lesion. Similarly, no statistical significance was found when the TNM stage of colorectal cancer was correlated to serum gastrin levels (Fig. 1). On the contrary, patients with infiltrated lymph nodes had higher gastrin levels than the pa- tients without metastases, with the results reaching statistical significance (53.6 pg/mL vs 41.06 pg/mL, P = 0.025). Discussion The role of H. pylori infection and hypergastrinemia in the development of colorectal carcinogenesis has been a matter of scientific debate, with controversial findings up to pres- ent. Gastrin is a 17-aminoacid polypeptide, produced by the G-cells of the gastric antrum, duodenum and pancreas. The hormone is involved in the secretion of gastric acid from the parietal cells of the stomach, as well as in the regulation of pancreatic enzyme activity and also appears to play an im- portant role in the modulation of gastric emptying [6]. As it comes to colorectal cancer, hypergastrinemia has been re- ported to be associated with increased risk for colorectal ma- lignancy, as the hormone is considered to serve as a growth factor of normal colonic epithelium [7-9]. In addition, it appears that patients with elevated gastrin levels due to Zollinger-Ellison syndrome have higher markers of colonic proliferation [10]. On the other hand, in a study by Orbuch et al (1996), performed similarly in patients with Zollinger-El- lison syndrome, the results showed no significant correlation between hypergastrinemia and increased risk of colorectal cancer [11]. Moreover, Bombski et al (2003) have demon- strated a decline in preoperatively elevated serum gastrin levels after curative surgical operations in colorectal cancer patients [12]. The exact mechanism through which gastrin acts in the progress of colorectal carcinogenesis remains a mat- ter of dispute. Many authors have suggested that gastrin is produced and secreted by the malignant intestinal cells and demonstrate its growth stimulation effects via autocrine or paracrine pathways [13, 14]. Focusing in a more molecular basis, recent studies have proven that gastrin is related to upregulation of expression of inflammatory mediators, such as COX-2 and IL-8, whose inhibition can contribute in the prevention of colorectal cancer development [15]. In addi- tion, there seems to be a genetic bridge between hypergas- trinemia and colorectal cancer, as gastrin expression is in- duced by the k-ras oncogene [16]. Lastly, there is a mounting scientific debate concerning the role of gastrin precursors, such as gastrin-gly, which seem to upregulate proangiogenic factors, like VEGF in colon cancer cells [17]. Based upon these recent data, it is not surprising that gastrin precursors and not gastrin itself may be involved in colorectal cancer, bridging the gap regarding the presence of hypergastrinemia in colorectal cancer patients. Nevertheless, the exact signifi- cance of gastrin or its precursors in colorectal cancer is still a field of scientific investigation and safe conclusions cannot be reached yet. Our results did not demonstrate a statistically significant difference of serum gastrin levels in the colorectal cancer group compared to controls. However, we did show that there was a statistically significant increase of serum gastrin in patients with lymph node metastases. The measurement of gastrin as a predictor of colorectal metastatic lesions in the liver has been proposed by Kameyama et al (1993) [18]. Moreover, the same research group has reported positive ef- fect of administration of gastrin antagonists after liver resec- tion due to colorectal metastatic disease [19]. Another matter of conflict remains the possible correla- tion of gastrin levels and colorectal cancer stage. Our study results were not supportive of a positive correlation between gastrin serum levels and the TNM stage of the tumor, as proposed in some published studies [20-22]. Similar con- clusions with our results have reached the study groups of Fontanesi et al. and Vanderstraeten et al [23, 24]. However, the clinical significance of these findings cannot at present be safely interpreted, since the underlying pathophysiological pathways remain terra incognita. Helicobacter pylori infection is one of the most common causes of hypergastrinemia and chronic atrophic gastritis and also is firmly associated with gastroduodenal ulceration, gastric carcinoma and lymphoma, with about 50% of the worldwide population being carriers of the pathogen [23]. In addition, H. pylori strains that express the cytoxin-associated gene (CagA+) are considered to further induce the inflam- matory stress in the colonized gastric mucosa, compared to the CagA- H. pylori strains, leading more frequently to the development of chronic atrophic gastritis, condition di- rectly related to elevation of gastrin levels, through reverse feedback regulation [24-26]. Moreover, if chronic atrophic gastritis is established, the following hypochlorhydria may result in intestinal overgrowth of acid-sensitive microflora, which has also been implicated in colorectal cancer progres- sion [27], fact that also proposes a potential link between colorectal cancer and elevated gastrin levels. The main pathogenic mechanisms which are considered to be involved include the occurring hypergastrinemia in cases of atrophic gastritis, as described above, the increase of the intraluminal ammonia products, which can trigger intracellular tumori- genic mechanisms, and finally the promotion of systemic inflammation, through overexpression of proinflammatory cytokines (IL-1, IL-8, TNF-α, etc) and growth factors (EGF, TGF-α, etc) [28]. It is accepted that H. pylori strains that express the cytoxin-associated gene (CagA+) are associated to even greater increase of local and systemic inflammation 174 Articles © The authors | Journal compilation © J Clin Med Res and Elmer Press™ | www.jocmr.org