Risk factors for gastroesophageal reflux disease and analysis of genetic contributors

Gastroesophageal reflux disease(GERD) is a common gastrointestinal disorder with an increasing prevalence. GERD develops when the reflux of stomach contents causes troublesome typical and atypical symptoms and/or complications. Several risk factors of GERD have been identified and evaluated over the years, including a considerable amount of genetic factors. Multiple mechanisms are involved in the pathogenesis of GERD including:(1) motor abnormalities, such as impaired lower esophageal sphincter(LES) resting tone, transient LES relaxations, impaired esophageal acid clearance and delayed gastric emptying; and(2) anatomical factors, such as hiatal hernia and obesity. Genetic contribution seems to play a major role in GERD and GERD-related disorders development such Barrett's esophagus and esophageal adenocarcinoma. Twin and family studies have revealed an about 31% heritability of the disease. Numerous single-nucleotide polymorphisms in various genes like FOXF1, MHC, CCND1, anti-inflammatory cytokine and DNA repair genes have been strongly associated with increased GERD risk. GERD, Barrett'sesophagus and esophageal adenocarcinoma share several genetic loci. Despite GERD polygenic basis,specific genetic loci such as rs10419226 on chromosome 19, rs2687201 on chromosome 3, rs10852151 on chromosome 15 and rs520525 on the paired related homeobox 1 gene have been mentioned as potential risk factors. Further investigation on the risk genes may elucidate their exact function and role and demonstrate new therapeutic approaches to this increasingly common disease.

Oxidative imbalance increases the risk for colonic polyp and colorectal cancer development

BACKGROUND The role of oxidative stress in the pathogenesis of colorectal carcinoma(CRC)has garnered considerable interest recently.Specific oxidative factors have been implicated in the pathogenesis of adenomatous polyps and ultimately adenocarcinoma.AIM To evaluate the effect of oxidative imbalance as quantified by specific serological markers in the development of sporadic colon adenocarcinoma.METHODS A total of 170 patients that underwent endoscopy of the lower gastrointestinal tract in a tertiary center within 3 years were included in the study.They were allocated in three groups;those with sporadic colon adenocarcinoma(n=56,32.9%),those with colonic polyps(n=33,19.4%)and healthy controls(n=81,47.7%).All patients were evaluated for oxidant activity and antioxidant capacity with serum measurements of specific markers such as vitamins A,25(OH)D3,E,C,B12,folic acid,glutathione,selenium(Se),zinc(Zn),free iron(Fe^(2+)),and malondialdehyde and results were compared between groups.RESULTS Serum levels of vitamins C,E,D,Se,Zn,vitamin B12 and total antioxidant capacity were significantly lower in the combined neoplasia/polyp group than in the control group(P=0.002,P=0.009,P<0.001,P<0.001,P<0.001,P=0.020 and P<0.001,correspondingly).Increased levels of vitamin E(P=0.004),vitamin D(P<0.001),Se(P<0.001)and Zn(P<0.001)seem to bestow a protective effect on the development of CRC.For vitamin D(P<0.001)and Zn(P=0.036),this effect seems to extend to the development of colon polyps as well.On the other hand,elevated serum levels of malondialdehyde are associated with a higher risk of CRC(OR=2.09 compared to controls,P=0.004).Regarding colonic polyp development,increased concentrations of vitaminΑand Fe^(2+) are associated with a higher risk,whereas lower levels of malondialdehyde with a lower risk.CONCLUSION Increased oxidative stress may play an important role in the pathogenesis and progression of CRC.Antioxidants’presence may exert a protective effect in the very early stages of colon carcinogenesis.