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Background: Macrophage capping protein (CAPG), an actin filament end-capping protein, plays an important role in regulation of cellular motility and structural rearrangement within cells and has been implicated with development of various types of cancer. Recent study demonstrated that a CAPG variant was associated with a rare fallopian tube tumor, albeit with a small sample size. The present study aimed to determine the association of CAPG variants with cancer susceptibility. Methods: Four non-synonymous single nucleotide variations (NSVs), rs2229668 (p.V41I), rs117284777 (p.K227R), rs200233412 (p.A229T) and rs6886 (p.R335H), in CAPG were retrieved from genotyping, by an exome-chip, in 2,317 consecutive autopsy cases (1,284 men and 1,033 women, mean age 80.7 years), in which the presence or absence of cancer was verified pathologically. The association of CAPG variants with presence of cancer and with different types of cancer was determined. Interaction with smoking was also determined. Results: There were 1,446 cancer-bearing and 897 cancer-free subjects. Among four SNVs, only p.R335H (c.1004C>T) was associated with the presence of cancer (adjusted OR=1.49, 95% CI=1.23-1.81, P=5.08 × 10-5). The association was found in men (adjusted OR=1.64, 95% CI=1.26-2.14, P=2.25 × 10-4), but not in women. Investigation with different types of cancer revealed that gastric cancer showed a positive association (adjusted OR=1.61, 95% CI=1.16-2.24, P=0.005) in men. The effect size of CAPG variants showed no difference between smokers and nonsmokers. Conclusions: Our study suggests that a non-synonymous SNV of CAPG, p.R335H, affects cancer susceptibility in men without interaction with smoking habit and that the SNV is associated with gastric cancer in men.

Association of Macrophage Capping Protein (CAPG) Arg335 his Polymorphism and Cancer Susceptibility in the Elderly Japanese