Serum Antibodies against Helicobacter pylori Neutrophil Activating Protein in Carriers of IL-4 C-590T Genetic Polymorphism Amplify the Risk of Gastritis and Gastric Cancer

Background: Gastric cancer arises, mainly, on an inflammatory background. Helicobocter pylori neutrophil activating [HP-NAP] protein functions as a potent pro-inflammatory mediator. Similarly, IL-4 plays a critical role in the inflammation pathway, the levels of which are altered by C to T transition at position -590 in its promoter region. Here, we have aimed to assess the risk of gastritis and gastric cancer in the co-presence of these two inflammation modulating mediators

Methods: Gastritis [n=58] and gastric cancer [n=31] patients were evaluated and compared with H. py/or/-positive asymptomatic controls [n=46], for serum antibodies against recombinant HP-NAP and IL-4 C-590T single nucleotide polymorphism using immunoblotting and PCR-RFLP, respectively. Multivariable logistic regression, adjusting for age, gender and ethnicity, was used for data analysis

Results: In terms of susceptibility to gastritis, seropositivity to HP-NAP projected a risk impact of 4.62 fold [OR=4.62, 95% Cl=l.50-14.22], which when present in IL-4 -590 T carriers augmented the risk up to 9.7 fold [OR=9.70, 95% CI=2.06-45.69]

A similar pattern, but of a stronger magnitude, occurred for the risk of gastric cancer, which was estimated at 9.07 fold [OR=9.07, 95% Cl=1.99-42.0] for HP-NAP-seropositive subjects and was drastically amplified [OR=33.64, 95% 0=2.06-548.68], when double-positive [HP-NAP seropositive/IL-4 -590 T carrier] subjects were examined against double negatives [HP-NAP seronegative/IL-4 -590 CC]

Conclusion: Our preliminary data indicate that serum antibodies against HP-NAP represent a state of risk, which is further exacerbated in IL-4 -590 T carriers. These biomarkers, if validated in larger prospective studies, can be used to screen for gastric cancer susceptibility

Age-specific gastric cancer risk indicated by the combination of Helicobacter pylori sero-status and serum pepsinogen levels

Serologic screening of gastric cancer [GC] by serum pepsinogens [sPG] levels and Helicobacter pylori [Hp] sero-status, though highly informative, has provided heterogeneous results. Here, we have evaluated the modifying effects of demographic factors on the risk impact of Hp sero-status/sPG levels in gastric cancer, with particular emphasis on age. A cross-sectional study was carried out on 1341 individuals [GC = 578, healthy = 763], who were stratified into two age groups: 35-59 years [middle-aged, n = 830] and >/= 60 years [60 years-plus, n = 511]. Demographic factors and serological states [Hp sero-staus and sPG levels] were recorded by subject interview and serum ELISAs, respectively. Covariate-specific odds ratios were calculated by multivariable logistic regression. Hp infection was consistently associated with increased sPGI and sPGII levels in the 60 year-plus, but not the middle-aged group. The joint examination of the variable states of the three serum biomarkers [Hp serology, sPGI, and sPGI/II ratio], in the 60 year-plus age group, demonstrated a stepwise escalation of risk from the single [sPGI[low]; OR = 2.6], to double [sPGI[low]/sPGI/II[low]; OR = 3.55, and Hp[positive]/sPGI[low]; OR = 5.0] and ultimately triple [Hp[positive]/PGI[low]/PGI/II[low]; OR = 10.48] positive states, in reference to the triple negatives. However, this pattern was not exhibited in the middle-aged subjects. Age was clearly identified as a modifying factor on the risk projection of the combined states of Hp serology and sPG levels in gastric cancer screening, reflected by the augmented [tilde10.5 fold] risk of GC in the triple positive [Hp[positive]/sPGI[low]/sPGI/II[low]] 60 year-plus subjects, which was not evident in the middle-aged group

Impact of methylenetetrahydrofolate reductase C677T polymorphism on the risk of gastric cancer and its interaction with helicobacter pylori infection

Attempts for early detection of gastric cancer have recently focused on host's genetic susceptibility factors and gene-environment interactions. We have, herein, studied the association of MTHFR C677T single nucleotide polymorphism [SNP] and its interaction with Helicobacter pylori infection, smoking, age and gender on the risk of gastric cancer among an Iranian population. Gastric cancer patients [n = 450] and cancer-free controls [n = 780] were studied for serum H. pylori-specific IgG antibodies by ELISA and MTHFR C677T polymorphism [SNP] by PCR-RFLP. Demographic and life style data were collected through patient interviews. Unconditional logistic regression model estimated odds ratio [OR] and the corresponding 95% confidence intervals [CI]. The interactions of MTHFR genotype with H. pylori infection [P = 0.03], age [P = 0.049] and gender [P = 0.007] were statistically significant. Accordingly, MTHFR C677T carriers who were also positive for H. pylori infection exhibited 80% [OR = 1.8, 95% CI = 1.0-2.9] significant excess risk of non-cardia gastric cancer. Furthermore, subjects over the age of 50 or female subjects carrying MTHFR C677T SNP showed 40 [OR = 1.4, 95% CI = 1.0-2.0] and 100 [OR = 2.0, 95% CI = 1.2-3.2] percent increased risk of gastric cancer, respectively. MTHFR C677T SNP seems to increase the risk of gastric cancer and the effect is significantly inflated by interactions with H. pylori infection, age and gender