Oral microbiome may play an important role in cancer pathogenesis. However, no study has prospectively investigated the association of the oral microbiome with subsequent risk of developing colorectal cancer (CRC). We conducted a nested case–control study including 231 incident CRC cases and 462 controls within the Southern Community Cohort Study with 75% of the subjects being African‐Americans. The controls were individually matched to cases based on age, ethnic group, smoking, season‐of‐study enrollment and recruitment method. Oral microbiota were assessed using 16S rRNA gene sequencing in pre‐diagnostic mouth rinse samples. Multiple bacterial taxa showed an association with CRC risk at p <0.05. Oral pathogens Treponema denticola and Prevotella intermedia were associated with an increased risk of CRC, with odds ratios (ORs) and 95% confidence intervals (CIs) of 1.76(1.19–2.60) and 1.55(1.08–2.22), respectively, for the individuals carrying these bacteria compared to non‐carriers. In the phylum Actinobacteria, Bifidobacteriaceae was more abundant among CRC patients than among controls. In the phylum Bacteroidetes, Prevotella denticola and Prevotella sp. oral taxon 300 were associated with an increased CRC risk, while Prevotella melaninogenica was associated with a decreased risk of CRC. In the phylum Firmicutes, Carnobacteriaceae, Streptococcaceae, Erysipelotrichaceae, Streptococcus, Solobacterium, Streptococcus sp. oral taxon 058 and Solobacterium moorei showed associations with a decreased risk of CRC. Most of these associations were observed among both African‐ and European‐Americans. Most of the associations were not significant after Bonferroni correction for multiple testing, which may be conservative. Our study suggests that the oral microbiome may play a significant role in CRC etiology.

Known risk variants explain only a small proportion of breast cancer heritability, particularly in Asian women. To search for additional genetic susceptibility loci for breast cancer, here we perform a meta-analysis of data from genome-wide association studies (GWAS) conducted in Asians (24,206 cases and 24,775 controls) and European descendants (122,977 cases and 105,974 controls). We identified 31 potential novel loci with the lead variant showing an association with breast cancer risk at P < 5 × 10 −8. The associations for 10 of these loci were replicated in an independent sample of 16,787 cases and 16,680 controls of Asian women (P < 0.05). In addition, we replicated the associations for 78 of the 166 known risk variants at P < 0.05 in Asians. These findings improve our understanding of breast cancer genetics and etiology and extend previous findings from studies of European descendants to Asian women.

Background DNA methylation plays a critical role in breast cancer development. Previous studies have identified DNA methylation marks in white blood cells as promising biomarkers for breast cancer. However, these studies were limited by low statistical power and potential biases. Using a new methodology, we investigated DNA methylation marks for their associations with breast cancer risk. Methods Statistical models were built to predict levels of DNA methylation marks using genetic data and DNA methylation data from HumanMethylation450 BeadChip from the Framingham Heart Study (n = 1595). The prediction models were validated using data from the Women’s Health Initiative (n = 883). We applied these models to genomewide association study (GWAS) data of 122 977 breast cancer patients and 105 974 controls to evaluate if the genetically predicted DNA methylation levels at CpG sites (CpGs) are associated with breast cancer risk. All statistical tests were two-sided. Results Of the 62 938 CpG sites CpGs investigated, statistically significant associations with breast cancer risk were observed for 450 CpGs at a Bonferroni-corrected threshold of P less than 7.94 × 10–7, including 45 CpGs residing in 18 genomic regions, that have not previously been associated with breast cancer risk. Of the remaining 405 CpGs located within 500 kilobase flaking regions of 70 GWAS-identified breast cancer risk variants, the associations for 11 CpGs were independent of GWAS-identified variants. Integrative analyses of genetic, DNA methylation, and gene expression data found that 38 CpGs may affect breast cancer risk through regulating expression of 21 genes. Conclusion Our new methodology can identify novel DNA methylation biomarkers for breast cancer risk and can be applied to other diseases.

Few studies have evaluated the relationship of oral microbiome with obesity. We investigated the oral microbiome among 647 obese and 969 non-obese individuals from the Southern Community Cohort Study, through 16S rRNA gene sequencing in mouth rinse samples. We first investigated 16 taxa in two probiotic genera, Bifidobacterium and Lactobacillus . Among them, eight showed nominal associations with obesity ( P < 0.05). Especially, Bifidobacterium (odds ratio [OR] = 0.67, 95% confidence interval [CI]:0.54, 0.83) and Bifidobacterium longum (OR = 0.57, 95% CI: 0.45, 0.73) were significantly associated with decreased obesity prevalence with false-discovery rate (FDR)-corrected P of 0.01 and 5.41 × 10 −4 , respectively. Multiple other bacterial taxa were also significantly associated with obesity prevalence at FDR-corrected P < 0.05. Among them, five in Firmicutes and two respectively in Actinobacteria and Proteobacteria were significantly associated with increased obesity prevalence. Significant associations with decreased obesity prevalence were observed for two taxa respectively in Actinobacteria and Firmicutes . Most of these taxa were associated with body mass index at study enrollment and weight gain during adulthood. Also, most of these associations were observed in both European- and African-Americans. Our findings indicate that multiple oral bacterial taxa, including several probiotic taxa, were significantly associated with obesity.

Background Few population-based studies have evaluated the influence of long-term diet on the gut microbiome, and data among Asian populations are lacking. Objective We examined the association of long-term diet quality, comprising 8 food groups (fruit, vegetables, dairy, fish/seafood, nuts/legumes, refined grains, red meat, and processed meat), with gut microbiome among Chinese adults. Methods Included were 1920 men and women, enrolled in 2 prospective cohorts (baseline 1996–2006), who remained free of cardiovascular diseases, diabetes, and cancer at stool collection (2015–2018) and had no diarrhea or antibiotic use in the last 7 d before stool collection. Microbiome was profiled by 16S rRNA sequencing. Long-term diet was assessed by repeated surveys at baseline and follow-ups (1996–2011), with intervals of 5.2 to 20.5 y between dietary surveys and stool collection. Associations of dietary variables with microbiome diversity and composition were evaluated by linear or negative binomial hurdle models, adjusting for potential confounders. False discovery rate (FDR) &lt;0.1 was considered significant. Results The mean ± SD age at stool collection was 68 ± 1.5 y. Diet quality was positively associated with microbiome α-diversity (P = 0.03) and abundance of Firmicutes, Actinobacteria, Tenericutes, and genera/species within these phyla, including Coprococcus, Faecalibacterium/Faecalibacterium prausnitzii, Bifidobacterium / Bifidobacterium adolescentis, and order RF39 (all FDRs &lt;0.1). Significant associations were also observed for intakes of dairy, fish/seafood, nuts/legumes, refined grains, and processed meat, including a positive association of dairy with Bifidobacterium and inverse associations of processed meat with Roseburia /Roseburia faecis. Most associations were similar, with or without adjustment for BMI and hypertension status or excluding participants with antibiotic use in the past 6 mo. Conclusion Among apparently healthy Chinese adults, long-term diet quality is positively associated with fecal microbiome diversity and abundance of fiber-fermenting bacteria, although magnitudes are generally small. Future studies are needed to examine if these bacteria may mediate or modify diet–disease relations.