Lifestyle Factors, Colorectal Tumor Methylation, and Survival Among African Americans and European Americans

Evan L Busch,Robert S Sandler,Temitope O Keku,Joseph A Galanko,Ajay Goel

doi:10.1038/s41598-018-27738-x

Abstract

Differences in tumor characteristics might partially account for mortality disparities between African American (AA) and European American (EA) colorectal cancer patients. We evaluated effect modification by race for exposure and patient-outcomes associations with colorectal tumor methylation among 218 AA and 267 EA colorectal cancer cases from the population-based North Carolina Colon Cancer Study. Tumor methylation was assessed in CACNA1G, MLH1, NEUROG1, RUNX3, and SOCS1. We used logistic regression to assess whether associations between several lifestyle factors—intake of fruits, vegetables, folate, and non-steroidal anti-inflammatory drugs—and tumor methylation were modified by race. Proportional hazards models were used to evaluate whether race modified associations between tumor methylation and time to all-cause mortality. Greater fruit consumption was associated with greater odds of high NEUROG1 methylation among EA at methylation cut points of 15–35% (maximum OR 3.44, 95% CI 1.66, 7.13) but not among AA. Higher folate intake was associated with lower odds of high CACNA1G methylation among EAs but not AAs. Tumor methylation was not associated with all-cause mortality for either group. Race might modify associations between lifestyle factors and colorectal tumor methylation, but in this sample did not appear to modify associations between tumor methylation and all-cause mortality.

Highlights

Another possible source of CRC tumor variation is differences in epigenetic profiles
For associations between dichotomous lifestyle factors and CACNA1G methylation (Table 2), among AA, higher vegetable consumption was associated with greater odds of a high methylation tumor when high methylation was defined by a cut point of 15% (OR = 2.95, 95% CI 1.10, 7.94) but not at other cut points
Higher intake of non-steroidal anti-inflammatory drugs (NSAIDs) among AA was associated with greater odds of a high methylation tumor at a methylation cut point of 5% (OR = 0.42, 95% CI 0.18, 0.97), but among European American (EA) we did not observe an association between NSAIDs intake and CACNA1G methylation

Summary

Introduction

Another possible source of CRC tumor variation is differences in epigenetic profiles. Lifestyle and dietary exposures such as fiber intake and smoking have been associated with CRC methylation in humans[8,9], and exposure to non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with CRC status of the CpG island methylator phenotype (CIMP)[10]. It is not clear whether associations between lifestyle and dietary exposures with methylation markers are modified by race, nor whether differences in CRC methylation by race might contribute to survival differences. In analyzing the methylation data, we used cut point analyses[13] to evaluate the etiologic and survivorship implications of different definitions of high versus low methylation for each marker

Methods

Results

Conclusion