The well differentiated intestinal type is sporadic and highly associated with environmental exposures, especially H. pylori infection (13). There are also biologic differences between these subtypes of gastric cancer that may guide treatment approaches. H2N is over expressed more often in the intestinal vs the diffuse type, 30% vs 6% in Inhibitors,research,lifescience,medical one study (14). The Beta-catenin/Wnt signaling pathway is also recognized to play a large role in the molecular carcinogenesis of the intestinal type cancer (15). Despite the genetic heterogeneity of gastric cancer, several
biological determinants of risk and prognosis have been identified. Genetic polymorphisms of cytokines released with “oxidative stress” such as IL-Iβ, IL-10, and TNF-A have been associated with increased gastric cancer risk (16)-(18). Over expression of the oncogenes, tie-1, CMET and AKT have been found to confer a poor prognosis Inhibitors,research,lifescience,medical in both subtypes (19)-(21). Tumor expression of the isoenzyme COX-2 is an independent prognostic factor for gastric cancer survival (22). This benefit may be mediated by a reduction in lymphangiogenesis, another correlate of prognosis
(22),(23). Recently Her-2/Neu over expression, an important predictive and prognostic factor in breast cancer has been independently associated with a poor prognosis in gastric cancer (24),(25). Inhibitors,research,lifescience,medical The prognostic significance of age, gender, and ethnicity in metastatic gastric cancer is unclear. The prevailing belief that young patients with gastric cancer have a more aggressive disease has been recently called into question (26),(27). Several prospective and population studies since 1996 have Inhibitors,research,lifescience,medical consistently shown that age is not a prognostic factor for survival, despite the higher prevalence of “diffuse type” cancer which typically has a worse outcome (28),(29). However, according to a recent population-based study of gastric cancer, a significant impact of age on survival was found in patients with Inhibitors,research,lifescience,medical stage IV disease (30). As compared to women, men are twice as likely to develop and die from gastric cancer, in the US (1). Although this may
represent varying environmental exposures between genders, studies demonstrate that menstrual factors such as age of menopause and years of fertility are associated with gastric cancer incidence (31). Phosphoprotein phosphatase Interestingly, woman may be more likely to have a “diffuse type histology” (32). There are also significant ethnic and racial differences in gastric cancer incidence and survival. Asian patients consistently have increased survival rates compared to their western counterparts (33). Ethnic Asians living in the US share this benefit which suggests that these differences are not likely treatment related (34). Other racial differences in the US are MG-132 clinical trial notable as the incidence and mortality is 50% higher in African Americans than Caucasians (35).