Lymphotoxin-alpha polymorphisms and presence of cancer in 1,536 consecutive autopsy cases

LTA polymorphisms C804A (rs1041981, T60N) and T495C (rs2229094, C13R) were determined in 1,536 consecutive autopsy cases and were registered in the Japanese single-nucleotide polymorphisms (SNPs) for geriatric research (JG-SNP) Internet database. Tumors were systematically reviewed, pathologically confirmed, and assessed in relation to LTA genotype.The study population consisted of 827 males and 709 females, with a mean age of 80 years. Altogether, we studied 606 subjects without cancer and 930 subjects with cancer of the stomach (n = 183), lung (n = 164), colon or rectum (n = 143), or other sites. The presence of cancer was higher in males than in females. The C804A and T495C polymorphisms were associated with cancer in males (CA + AA: CC, adjusted OR = 0.72, 95% CI = 0.53 – 0.99; TC + CC: TT, adjusted OR = 1.45, 95% CI = 1.04 – 2.02; respectively) but not in females. In males, the C804A polymorphism was associated with lung cancer (CA + AA: CC, adjusted OR = 0.60, 95% CI = 0.37 – 0.97), whereas the T495C polymorphism was associated with gastric cancer (TC + CC: TT, adjusted OR = 1.68, 95% CI = 1.06 – 2.65).We found some evidence of an association between LTA polymorphisms and cancer risk in elderly Japanese men. Further studies in larger populations should examine this hypothesis.Elderly people often experience chronic and low-grade inflammation, whereupon the levels of certain inflammatory serum markers (e.g., C-reactive protein) and pro-inflammatory cytokines (e.g., tumor necrosis factor-alpha and interleukin-6) are elevated. However, increases in circulating inflammatory markers are often not noticeable in healthy elderly persons and are much below the levels experienced during acute infections [1,2]. Moreover, it is well known that the prevalence of cancer increases sharply with age, and that the majority of cancer cases occur in patients over the age of 65 [3]. Persistent inflammation is thought to trigger certain cancers, particularly those of the stomach, c