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Background: The MHC class I chain-related protein A (MICA) and protein B (MICB) participate in tumor immunosurveillance and may be important in colorectal cancer, but have not been examined in colorectal cancer development. Methods: sMICA and sMICB blood levels were measured by SomaScan in Visit 2 (1990–92, baseline) and Visit 3 (1993–95) samples in cancer-free participants in the Atherosclerosis Risk in Communities Study. We selected rs1051792, rs1063635, rs2516448, rs3763288, rs1131896, rs2596542, and rs2395029 that were located in or in the vicinity of MICA or MICB and were associated with cancer or autoimmune diseases in published studies. SNPs were genotyped by the Affymetrix Genome-Wide Human SNP Array. We applied linear and Cox proportional hazards regressions to examine the associations of preselected SNPs with sMICA and sMICB levels and colorectal cancer risk (236 colorectal cancers, 8,609 participants) and of sMICA and sMICB levels with colorectal cancer risk (312 colorectal cancers, 10,834 participants). In genetic analyses, estimates adjusted for ancestry markers were meta-analyzed. Results: Rs1051792-A, rs1063635-A, rs2516448-C, rs3763288-A, rs2596542-T, and rs2395029-G were significantly associated with decreased sMICA levels. Rs2395029-G, in the vicinity of MICA and MICB, was also associated with increased sMICB levels. Rs2596542-T was significantly associated with decreased colorectal cancer risk. Lower sMICA levels were associated with lower colorectal cancer risk in males (HR = 0.68; 95% confidence interval, 0.49–0.96) but not in females (Pinteraction = 0.08). Conclusions: Rs2596542-T associated with lower sMICA levels was associated with decreased colorectal cancer risk. Lower sMICA levels were associated with lower colorectal cancer risk in males. Impact: These findings support an importance of immunosurveillance in colorectal cancer.

Supplemental Table 2 shows the associations between pre-selected SNPs and Visit 2 sMICA and sMICB levels (continuous variables) stratified by sex, race, or diabetes status.

Supplemental Table 4 shows the associations of Visit 2 sMICA and sMICB levels (in quartiles) with CRC risk.

Supplemental Table 3 shows the associations between pre-selected SNPs and CRC risk stratified by sex, race, or diabetes status.

Supplemental Table 8 shows the associations of pre-selected SNPs with Visit 2 sMICA and sMICB levels and CRC risk without adjustment for ancestry markers.

Background:The MHC class I chain-related protein A (MICA) and protein B (MICB) participate in tumor immunosurveillance and may be important in colorectal cancer, but have not been examined in colorectal cancer development.Methods:sMICA and sMICB blood levels were measured by SomaScan in Visit 2 (1990–92, baseline) and Visit 3 (1993–95) samples in cancer-free participants in the Atherosclerosis Risk in Communities Study. We selected rs1051792, rs1063635, rs2516448, rs3763288, rs1131896, rs2596542, and rs2395029 that were located in or in the vicinity of MICA or MICB and were associated with cancer or autoimmune diseases in published studies. SNPs were genotyped by the Affymetrix Genome-Wide Human SNP Array. We applied linear and Cox proportional hazards regressions to examine the associations of preselected SNPs with sMICA and sMICB levels and colorectal cancer risk (236 colorectal cancers, 8,609 participants) and of sMICA and sMICB levels with colorectal cancer risk (312 colorectal cancers, 10,834 participants). In genetic analyses, estimates adjusted for ancestry markers were meta-analyzed.Results:Rs1051792-A, rs1063635-A, rs2516448-C, rs3763288-A, rs2596542-T, and rs2395029-G were significantly associated with decreased sMICA levels. Rs2395029-G, in the vicinity of MICA and MICB, was also associated with increased sMICB levels. Rs2596542-T was significantly associated with decreased colorectal cancer risk. Lower sMICA levels were associated with lower colorectal cancer risk in males (HR = 0.68; 95% confidence interval, 0.49–0.96) but not in females (Pinteraction = 0.08).Conclusions:Rs2596542-T associated with lower sMICA levels was associated with decreased colorectal cancer risk. Lower sMICA levels were associated with lower colorectal cancer risk in males.Impact:These findings support an importance of immunosurveillance in colorectal cancer.

Supplemental Table 1 shows the results from previous studies that found significant associations between the pre-selected SNPs and risk of cancers or autoimmune diseases.

Supplemental Table 7 shows the association of sMICA and sMICB levels (continuous variables) and pre-selected SNPsa with risk of CRC stratified by family history of CRC.

Supplemental Table 9 shows the associations between pre-selected SNPs and mean of Visit 2 and Visit 3 sMICA and sMICB levels (continuous variables).

Supplemental Table 6 shows the associations of sMICA and sMICB levels (continuous variables) and pre-selected SNPsb with risk of CRC and subtypes of CRC.

Supplemental table 5 shows the associations between pre-selected SNPs and risk of CRC with and without adjustment for sMICA and sMICB levels.

Background: Several bacterial taxa that are consistently enriched in the gut microbiome of CRC cases are also found in the oral cavity. They exhibit phenotypic traits such as adherence to host epithelial cells, mucus degradation, and biofilm formation, which promote bacterial survival in the colon and may play a role in both oral disease and colorectal carcinogenesis by stimulating an inflammatory response. We evaluated the effect of a 6-week aspirin intervention on the relative abundance of oral bacterial taxa in a randomized placebo-controlled trial. Methods: Fifty healthy subjects, 50-75 years old, were randomized to receive either aspirin (N=30) or placebo (N=20) for 6 weeks. Oral samples were collected at baseline and after treatment (6 weeks) and amplicon sequencing of the V4 region of the 16S rRNA gene was done using Illumina MiSeq technology. The data were analyzed using the standard DADA2 workflow. We used linear regression analysis, PERMANOVA, and negative binomial regressions (DESeq2 package) to assess the association between intervention assignment (aspirin vs. placebo) and α-diversity, β-diversity, and fold change in specific taxa, after adjustment for age, gender, and BMI at baseline and postintervention. Intervention assignment was hypothesized to influence the following bacterial taxa a priori: Fusobacterium, Porphyromonas, Prevotella, Gemella, Neisseria, Streptococcus, Haemophilus, Campylobacter, Veillonella, Actinomyces based on previous studies. We estimated the association between aspirin use and the changes in the relative abundance of the specified taxa from pre- to post-treatment (baseline to week 6) using a mixed-effect regression model (lme4 package) with a binomial distribution in which the log of odds ratio (β estimate) for the interaction term compared aspirin to placebo intervention for post- versus pretreatment. Results: Aspirin treatment was not associated with α- or β- diversity at baseline or postintervention. However, the change in relative abundance of 8 out of the 10 prespecified taxa over time differed between the aspirin and placebo groups. In the aspirin group, there were greater increases in the relative abundances of Neisseria, Streptococcus, Actinomyces, and greater decreases in the relative abundance of Prevotella, Veillonella, Fusobacterium, and Porphyromonas. Conclusions: These preliminary findings suggest that aspirin may change the relative abundance of oral taxa associated with oral dysbiosis or CRC. Further studies are needed to understand the impact that the duration and dosage of the aspirin intervention may have on the oral microbiome. Citation Format: Guillaume C. Chinedu, Christopher M. Staley, Ryan T. Demmer, Shaukat Aasma, Tim R. Church, Anna E. Prizment. Effects of aspirin intervention on health and disease-associated oral bacterial taxa [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr A04.