Background: Colorectal cancer is common worldwide and chemoprevention has the potential of reducing the number of individuals who may suffer and perish from this disease. Methods: A randomized placebo controlled pilot study in colorectal cancer patients was performed using calcium carbonate as the test agent in a multi-institutional oncology study group. Results: Two hundred twenty volunteers were randomized in the study. The primary goals of compliance, accrual, and toxicity monitoring are presented. Presence of multiple adenomas at study entry and subsequent development of metachronous adenomas were recorded and found to be associated with synchronous adenomas. The secondary endpoint of recurrent adenomas indicated lower rates of new adenoma in the volunteers randomized to the calcium group. Conclusion: This pilot study indicates the feasibility of enrolling survivors of colorectal cancer as study volunteers in a colorectal neoplasm chemoprevention clinical trial and oral calcium continues to be a potentially effective drug in reducing colorectal adenomas. © 2011 Elsevier Inc. All rights reserved.

Background

While strong evidence supports adverse maternal and offspring consequences of air pollution, mechanisms that involve the placenta, a key part of the intrauterine environment, are largely unknown. Previous studies of air pollution and placental gene expression were small candidate gene studies that rarely considered prenatal windows of exposure or the potential role of offspring sex. We examined overall and sex-specific associations of prenatal exposure to fine particulate matter (PM_2.5) with genome-wide placental gene expression.

Methods

Participants with placenta samples, collected at birth, and childhood health outcomes from CANDLE (Memphis, TN) (n = 776) and GAPPS (Seattle, WA) (n = 205) cohorts of the ECHO-PATHWAYS Consortium were included in this study. PM_2.5 exposures during trimesters 1, 2, 3, and the first and last months of pregnancy, were estimated using a spatiotemporal model. Cohort-specific linear adjusted models were fit for each exposure window and expression of >11,000 protein coding genes from paired end RNA sequencing data. Models with interaction terms were used to examine PM_2.5-offspring sex interactions. False discovery rate (FDR < 0.10) was used to correct for multiple testing.

Results

Mean PM_2.5 estimate was 10.5-10.7 μg/m³ for CANDLE and 6.0-6.3 μg/m³ for GAPPS participants. In CANDLE, expression of 13 (11 upregulated and 2 downregulated), 20 (11 upregulated and 9 downregulated) and 3 (2 upregulated and 1 downregulated) genes was associated with PM_2.5 in the first trimester, second trimester, and first month, respectively. While we did not find any statistically significant association, overall, between PM_2.5 and gene expression in GAPPS, we found offspring sex and first month PM_2.5 interaction for DDHD1 expression (positive association among males and inverse association among females). We did not observe PM_2.5 and offspring sex interactions in CANDLE.

Conclusion

In CANDLE, but not GAPPS, we found that prenatal PM_2.5 exposure during the first half of pregnancy is associated with placental gene expression.