The association of lymphotoxin-beta receptor with the subsequent diagnosis of incident gastrointestinal cancer: results from the Dallas Heart Study

Background: Lymphotoxin-beta receptor (LTbetaR) is an immunological protein associated with inflammation, and from preclinical studies is implicated in tumorigenesis. The epidemiological relationships with cancer are unknown, hence this study investigated their associations. Methods: From a multiethnic population-based cohort, 3,032 participants without a prevalent cancer (a diagnosis prior to or within one year of enrollment) at baseline underwent measurement of plasma LTbetaR. These participants were followed for incident cancer using the Texas Cancer Registry (TCR). Results: Over a median follow-up of 12.1 years, 178 participants developed incident cancer, of which 30 participants developed incident gastrointestinal (GI) cancer. Median plasma LTbetaR (1.10 vs. 1.00 ng/mL, P<0.02) levels were higher in individuals with overall incident cancer compared to those without cancer. After adjustments for age, sex, and race/ethnicity, these relationships were no longer significant. When analyses were stratified by cancer type, LTbetaR was positively associated with GI cancer after adjustments: HR, 95% CI per 1-standard deviation increase in concentration 2.64 (1.23-5.68), P=0.013. LTbetaR stratified by quartiles was significantly associated temporally with the risk of incident GI cancer, log-rank: P=0.011. The median interval to incident GI cancer diagnosis was 5.9 years. Conclusions: Increased plasma levels of LTbetaR are associated with the development of GI cancer. The antecedent findings years prior to a subsequent diagnosis of incident GI cancer suggest a role for LTbetaR in the pathogenesis of GI cancer. Further studies are needed to determine if LTbetaR can serve as an immune biomarker for GI cancer, in particular hepatocellular and colorectal cancers.