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

Gastrointestinal tumor board: an evolving experience in Tehran Cancer Institute

Gastrointestinal [GI] cancers are a significant source of morbidity and mortality in Iran, with stomach adenocarcinoma as the most common cancer in men and the second common cancer in women. Also, some parts of Northern Iran have one of the highest incidences of esophageal cancer in the world. Multi-disciplinary organ-based joint clinics and tumor boards are a well-recognized necessity for modern treatment of cancer and are routinely utilized in developed countries, especially in major academic centres. But this concept is relatively new in developing countries, where cancer treatment centres are burdened by huge loads of patients and have to cope with a suboptimum availability of resources and facilities. Cancer Institute of Tehran University of Medical Sciences is the oldest and the only comprehensive cancer treatment centre in Iran, with a long tradition of a general tumor board for all cancers. But with the requirements of modern oncology, there has been a very welcome attention to sub-specialized organ-based tumor boards and joint clinics here in the past few years. Considering this, we started a multi-disciplinary tumor board for GI cancers in our institute in early 2010 as the first such endeavor here. We hereby review this 2-year evolving experience. The process of establishment of a GI tumor board, participations from different oncology disciplines and related specialties, the cancers presented and discussed in the 2 years of this tumor board, the general intents of treatment for the decisions made and the development of interest in this tumor board among the Tehran oncology community will be reviewed. The GI tumor board of Tehran Cancer Institute started its work in January 2010, with routine weekly sessions. A core group of 2 physicians from each surgical, radiation and medical oncology departments plus one gastroenterologist, GI pathologist and radiologist was formed, but participation from all interested physicians was encouraged. An electronic database was kept from the beginning. The number of patients presented in the tumor board increased from 4 in January 2010 to 16 in December 2011. Most patients were presented by radiation oncology department [38%] and then surgical [36%] and medical oncology [20%] departments. Physicians' participation also grew from an average of 8 each session to 12 in the same months, with a number of cancer specialists taking part from other university hospitals in Tehran. A total number of 225 patients were presented with a treatment decision made in this 2-year period. The majority of cases were colorectal [32%], stomach [23%], and esophageal [17%] cancers. The number of pancreatic [7%] and hepatobiliary [6%] cancers were much smaller. Most decisions were for a primary treatment [surgery or radiochemotherapy] and then a neoadjuvant approach. Tehran Cancer Institute's GI tumor board is one of the first multi-disciplinary organ-based tumor boards in Iran, and as such has made a successful start, establishing itself as a recognized body for clinical decisions and consultations in GI oncology. This experience is growing and evolving, with newer presentation and discussion formats and adapted guidelines for treatment of GI cancers in Iran sought

[Association between human papillomavirus [HPV] and breast cancer in Iranian patients]

Viruses, such as human Papillomavirus [HPV], have been detected in benign breast tissues and breast tumors and are considered to be involved in the etiology of breast cancer, but there are controversial data on the meaning of viral induction of breast cancer. The aim of this study was to investigate the presence of human Papillomavirus [HPV] in Iranian patients with breast carcinoma. In this case- control study, paraffin-embedded sections from 64 female patients with breast carcinoma and 53 breast tissues from patients with fibrocystic disease, as control, were analyzed for presence of HPV DNA. Real-Time PCR was used to amplify consensus GP5+/GP6+ HPV sequences. HPV DNA sequences were detected in 3 of the 53 benign breast tissue samples, but none of the breast carcinoma samples was identified. Our analysis could not confirm a role of HPV in breast cancer

Menetrier's disease presenting with ulcerative colitis: a case report and review of the literature

Menetrier's disease or hypertrophic gastritis is a premalignant rare disease that often presents with hypertrophy in the gastric folds, hypoalbuminemia and decreased acid secretion. There are a few papers worldwide that report concomitant Menetrier's disease and ulcerative colitis [U. C], however none are from Iran. This is the first case reported in Iranian literature. The pathogenesis of this coexistence is unknown. We report the case of a 28-year-old woman with intermittent bilateral edema of the lower extremities, weight loss and epigastric pain associated with chronic intermittent diarrhea and one episode of nocturnal dysentery. Paraclinical evaluations showed hypoalbuminemia, low serum protein level, severe 25 OH vitamin D deficiency, a positive Helicobacter pylori urea breath test and negative cytomegalovirus [CMV] IgM antibody. Histologic, radiologic and endoscopic findings were consistent with Menetrier's disease associated with U. C. The patient was prescribed mesalazine, asacol suppositories and pantoprazole. During a follow up visit the patient noted improvement in her symptoms. She was referred to a surgeon to discuss additional possible therapeutic treatments

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