Background: There are limited numbers of reports on the association of lymphotoxin-alpha (LTA) genotypes with gastric cancer.
Methods: A nested case-control study was carried out in the longitudinal cohort of atomic bomb survivors using stored sera before diagnosis (mean, 2.3 years) and blood cells. Enrolled were 287 cases with noncardia gastric cancer of diffuse and intestinal types and three controls per case selected from cohort members matched on age, gender, city, and time and type of serum storage and counter-matched on radiation dose.
Results: LTA 252GG and GA genotypes were associated with the prevalence of Helicobacter pylori IgG seropositivity and higher antibody titer against H. pylori cytotoxin-associated gene A (CagA) protein in controls and they were an independent risk factor for noncardia gastric cancer of diffuse type (RR = 2.8 (95% CI: 1.3-6.3), p = .01, and RR = 2.7 (95% CI: 1.5-4.8), p < .001), but not for intestinal type, after adjusting for H. pylori IgG seropositivity, CagA antibody titers, chronic atrophic gastritis, smoking, and radiation dose. Cessation of smoking (RR = 0.4 (95% CI: 0.2-0.7), p < .001) and never smoking (RR = 0.4 (95% CI: 0.3-0.6), p < .001) were both protective for future noncardia gastric cancer. Radiation dose was associated with noncardia gastric cancer in subjects with both the LTA 252G-allele and never smoking/quit smoking histories (RR = 3.8 (95% CI: 1.7-5.9), p = .009).
Conclusion: The LTA 252 genotype is associated with noncardia gastric cancer of diffuse type in Japan and interacted with radiation dose.