Dietary Patterns and Risk of Colorectal Cancer Subtypes Classified by Fusobacterium nucleatum in Tumor Tissue

Importance—Fusobacterium nucleatum appears to play a role in colorectal carcinogenesis through suppression of host immune response to tumor. Evidence also suggests that diet influences intestinal F. nucleatum. However, the role of F. nucleatum in mediating the relationship between diet and the risk of colorectal cancer is unknown. Objective—To test the hypothesis that the associations of prudent diets (rich in whole grains and dietary fiber) and Western diets (rich in red and processed meat, refined grains, and desserts) with colorectal cancer risk may differ according to the presence of F. nucleatum in tumor tissue. Design—Prospective cohort study. Setting—The Nurses’ Health Study (1980–2012) and the Health Professionals Follow-up Study (1986–2012). Participants—121,700 US female nurses and 51,529 US male health professionals aged 30 to 55 years and 40 to 75 years, respectively, at enrollment. Exposures—Prudent and Western dietary patterns. Main Outcomes and Measures—Incidence of colorectal carcinoma subclassified by F. nucleatum status in tumor tissue, determined by quantitative polymerase chain reaction. Results—We documented 1,019 incident colon and rectal cancer cases with available F. nucleatum data among predominantly white 137,217 individuals over 26–32 years of follow-up encompassing 3,643,562 person-years. The association of prudent diet with colorectal cancer significantly differed by tissue F. nucleatum status (Pheterogeneity = .01). Prudent diet score was associated with a lower risk of F. nucleatum-positive cancers [Ptrend = .003; multivariable hazard ratio of 0.43 (95% confidence interval 0.25–0.72) for the highest vs. the lowest prudent score quartile], but not with F. nucleatum-negative cancers (Ptrend = .47). Dietary component analyses suggested possible differential associations for the cancer subgroups according to intakes of dietary fiber (Pheterogeneity = .02). There was no significant heterogeneity between the subgroups according to Western dietary pattern scores (Pheterogeneity = .23). Conclusions and Relevance—Prudent diets rich in whole grains and dietary fiber are associated with a lower risk for F. nucleatum-positive colorectal cancer but not F. nucleatum-negative cancer, supporting a potential role for intestinal microbiota in mediating the association between diet and colorectal neoplasms

Analysis of the transcriptome in molecular epidemiology studies

The human transcriptome is complex, comprising multiple transcript types, mostly in the form of non-coding RNA (ncRNA). The majority of ncRNA is of the long form (lncRNA, ≥200bp), which plays an important role in gene regulation through multiple mechanisms including epigenetics, chromatin modification, control of transcription factor binding, and regulation of alternative splicing. Both mRNA and ncRNA exhibit additional variability in the form of alternative splicing and RNA editing. All aspects of the human transcriptome can potentially be dysregulated by environmental exposures. Next-generation RNA sequencing (RNA-Seq) is the best available methodology to measure this although it has limitations, including experimental bias. The third phase of the MicroArray Quality Control Consortium project (MAQC-III), also called Sequencing Quality Control (SeQC), aims to address these limitations through standardization of experimental and bioinformatic methodologies. A limited number of toxicogenomic studies have been conducted to date using RNA-Seq. This review describes the complexity of the human transcriptome, the application of transcriptomics by RNA-Seq or microarray in molecular epidemiology studies, and limitations of these approaches including the type of cell or tissue analyzed, experimental variation, and confounding. By using good study designs with precise, individual exposure measurements, sufficient power and incorporation of phenotypic anchors, studies in human populations can identify biomarkers of exposure and/or early effect and elucidate mechanisms of action underlying associated diseases, even at low doses. Analysis of datasets at the pathway level can compensate for some of the limitations of RNA-Seq and, as more datasets become available, will increasingly elucidate the exposure-disease continuum