Faculty Bibliography

In a cohort of 29,584 residents of Linxian, China, followed from 1985 to 2001, we conducted a case-cohort study of the magnitude of the association of Helicobacter pylori seropositivity with cancer risk in a random sample of 300 oesophageal squamous cell carcinomas, 600 gastric cardia adenocarcinomas, all 363 diagnosed gastric non-cardia adenocarcinomas, and a random sample of the entire cohort (N=1050). Baseline serum was evaluated for IgG antibodies to whole-cell and CagA H. pylori antigens by enzyme-linked immunosorbent assay. Risks of both gastric cardia and non-cardia cancers were increased in individuals exposed to H. pylori (Hazard ratios (HRs) and 95% confidence intervals=1.64; 1.26-2.14, and 1.60; 1.15-2.21, respectively), whereas risk of oesophageal squamous cell cancer was not affected (1.17; 0.88-1.57). For both cardia and non-cardia cancers, HRs were higher in younger individuals. With longer time between serum collection to cancer diagnosis, associations became stronger for cardia cancers but weaker for non-cardia cancers. CagA positivity did not modify these associations. The associations between H. pylori exposure and gastric cardia and non-cardia adenocarcinoma development were equally strong, in contrast to Western countries, perhaps due to the absence of Barrett's oesophagus and oesophageal adenocarcinomas in Linxian, making all cardia tumours of gastric origin, rather than a mixture of gastric and oesophageal malignancies.

BACKGROUND: Single nucleotide polymorphism association studies among cases and controls have been widely used for genetic analysis. The pyrosequencing method is based on indirect luminometric quantification of the pyrophosphate that is released as a result of nucleotide incorporation onto an amplified template. It has the advantages of accuracy, flexibility, automatization and speed when compared with PCR-RFLP method. AIM: To develop a protocol for allele frequency determination using pyrosequencing technology in the detection of the polymorphism at position -31 of the interleukin-1beta (IL-1beta) gene. METHODS: 162 patients (F/M = 0.93) who were enrolled at the Hospital Universitario Dr 'Jose Eleuterio Gonzalez' were studied. 123 patients had non-ulcer dyspepsia and 39 had histologically confirmed gastric cancer (GC). The polymorphism of IL-1beta -31 was determined by both RFLP and pyrosequencing methods. PCR-RFLP method used Alul restriction endonuclease. The same specific primers for PCR-RFLP and pyrosequencing were used for initial amplification and an additional biotinylated specific primer was designed for sequencing. RESULTS: 157 (96.9%) samples were clearly typed by the pyrosequencing method and the results were in accordance with the results of the PCR-RFLP method. The results of 5 samples (3.1%) were not in accordance between both methods. Two of them were T/T and 2 were C/T by sequencing method and all four were C/C by RFLP. Another sample was C/ C by sequencing and T/T by RFLP. CONCLUSION: The pyrosequencing method is not only suitable for the IL-1beta -31 genotyping but is a fast and unexpensive way of genotyping since requires smaller amounts of DNA, and required significantly less time in the generation of results than the RFLP technique. The protocol developed is useful for the typing of the IL-1beta -31 polymorphism

BACKGROUND: Cancer may follow exposure to an environmental agent after many decades. The bacterium Helicobacter pylori, known to be acquired early in life, increases risk for gastric adenocarcinoma, but other factors are also important. In this study, we considered whether early-life family structure affects the risk of later developing gastric cancer among H. pylori+ men. METHODS AND FINDINGS: We examined a long-term cohort of Japanese-American men followed for 28 y, and performed a nested case-control study among those carrying H. pylori or the subset carrying the most virulent cagA+ H. pylori strains to address whether family structure predicted cancer development. We found that among the men who were H. pylori+ and/or cagA+ (it is possible to be cagA+ and H. pylori- if the H. pylori test is falsely negative), belonging to a large sibship or higher birth order was associated with a significantly increased risk of developing gastric adenocarcinoma late in life. For those with cagA+ strains, the risk of developing gastric cancer was more than twice as high (odds ratio 2.2; 95% confidence interval 1.2-4.0) among those in a sibship of seven or more individuals than in a sibship of between one and three persons. CONCLUSIONS: These results provide evidence that early-life social environment plays a significant role in risk of microbially induced malignancies expressing five to eight decades later, and these findings lead to new models to explain these interactions

The mode of transmission of Helicobacter pylori infection is poorly characterized. In northern California, 2,752 household members were tested for H. pylori infection in serum or stool at a baseline visit and 3 months later. Among 1,752 person considered uninfected at baseline, 30 new infections (7 definite, 7 probable, and 16 possible) occurred, for an annual incidence of 7% overall and 21% in children <2 years of age. Exposure to an infected household member with gastroenteritis was associated with a 4.8-fold (95% confidence interval [CI] 1.4-17.1) increased risk for definite or probable new infection, with vomiting a greater risk factor (adjusted odds ratio [AOR] 6.3, CI 1.6-24.5) than diarrhea only (AOR 3.0, p = 0.65). Of probable or definite new infections, 75% were attributable to exposure to an infected person with gastroenteritis. Exposure to an H. pylori-infected person with gastroenteritis, particularly vomiting, markedly increased risk for new infection

BACKGROUND: Colonization with Helicobacter pylori is a risk factor for gastric adenocarcinoma, but the magnitude of this association and its relationship to anatomic location of the cancer, duration of follow-up, age at diagnosis, histologic subtype, and H. pylori strain differences are less clear. We conducted a prospective nested case-control study of H. pylori serology to address these questions. METHODS: Case and control subjects were selected from the 29,133 50- to 69-year-old males recruited into the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. At baseline, detailed demographic data and a serum sample were collected. From 1985 to 1999, 243 incident cases of gastric adenocarcinoma were diagnosed in cohort members. Serum samples from 234 case subjects (173 with noncardia gastric cancers and 61 with gastric cardia cancers) and 234 age-matched control subjects were assayed for antibodies against H. pylori whole-cell and CagA antigens. We fit conditional logistic regression models to estimate the unadjusted and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the association of H. pylori seropositivity, defined as seropositivity to either whole-cell or CagA antigens, with noncardia gastric and gastric cardia cancers. All statistical tests were two-sided. RESULTS: H. pylori seropositivity was strongly associated with the risk of noncardia gastric cancer (adjusted OR = 7.9, 95% CI = 3.0 to 20.9) but was inversely associated with the risk of gastric cardia cancer (adjusted OR = 0.31, 95% CI = 0.11 to 0.89). H. pylori seropositivity rates did not vary statistically significantly by length of follow-up, age at diagnosis, or histologic subtype. A calculation of rates showed that the absolute risks of noncardia gastric and cardia gastric adenocarcinomas in the H. pylori-positive participants of this cohort would be 63 and 12 per 100,000 person-years, respectively, whereas corresponding rates in H. pylori-negative participants would be 8 and 37 per 100,000 person-years, respectively. CONCLUSION: H. pylori is a strong risk factor for noncardia gastric cancer but is inversely associated with the risk of gastric cardia cancer. These findings bolster the hypothesis that decreasing H. pylori prevalence during the past century may have contributed to lower rates of noncardia cancer and higher rates of cardia cancer in Western countries

AIM: To determine prevalence of H pylori infection in symptomatic children in Buenos Aires, Argentina, and to investigate factors associated with H pylori positivity. METHODS: A total of 395 children with upper gastrointestinal symptoms referred to the Gastroenterology Unit of the Children Hospital 'Sor Maria Ludovica' were evaluated for the presence of H pylori by the (13)C-Urea Breath Test ((13)C-UBT). A questionnaire was applied to the recruited population. RESULTS: Prevalence of H pylori infection was 40.0% in this population (mean age 9.97 +/- 3.1 years). The factors associated with H pylori positivity were number of siblings (P < 0.001), presence of pet cats (P = 0.03) and birds (P = 0.04) in the household, and antecedents of gastritis among family members (P = 0.01). After multivariate analysis, number of siblings [Odds ratio (OR) = 1.39; 95% CI, 1.20-1.61] and contact with pet cats (OR = 1.76; 95% CI, 1.00-3.09) remained as variables associated with H pylori infection. CONCLUSION: The prevalence of H pylori infection in children with upper gastrointestinal symptoms in Argentina was similar to that reported in developed countries. Children from families with a higher crowding index and presence of pet cats have a higher risk of being colonized with H pylori

GOAL: To study the feasibility of using repeat esophagogastroduodenoscopy (EGD) to screen for Helicobacter pylori infection and gastric cancer in an Asian immigrant cohort. BACKGROUND: Immigrants in the United States (US) from countries with high per capita rates of gastric cancer remain at higher risk for gastric cancer. The existence of the possibly modifiable risk factor of H. pylori infection and the poor outcomes associated with late-stage disease make screening higher-risk groups with EGD an appealing possibility. It is unknown whether Asian immigrants in the US would accept an EGD-based strategy for gastric cancer screening. STUDY: Cross-sectional study of adult Chinese immigrants in New York City with dyspepsia who underwent EGD in an earlier gastric cancer detection study, who were offered a second EGD four years later. Our main outcome measure was acceptance or refusal of repeat EGD. RESULTS: Seventy-three of the 115 Chinese participants in the earlier study were successfully contacted for this current study. Twenty-three of 73 (32%) underwent repeat EGD. Leading reasons given for declining were lack of symptoms and lack of time. Significantly associated with acceptance of repeat EGD was the belief that EGD will find stomach cancer 'nearly always' in someone who has it (P=0.0054; odds ratio=14.0, 2.1 to 94.2 95% confidence interval). CONCLUSIONS: Acceptance of repeat EGD for gastric cancer detection in a cohort of Chinese immigrants was relatively low despite the mitigation of cost and language factors, 2 major barriers to healthcare access. Relocation seemed to be a factor as well. In this population, perceptions of the benefits of EGD may influence acceptance of testing for cancer detection purposes