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Environmental Factor, August 2015

Extramural papers of the month

By Nancy Lamontagne

Prenatal DDT exposure linked with increased breast cancer risk

A new study, funded in part by NIEHS, found that women exposed prenatally to higher levels of the pesticide dichlorodiphenyltrichloroethane (DDT) were nearly four times more likely to develop breast cancer as adults than women exposed to lower levels before birth. During the 1960s, DDT was used widely in the U.S., and women prenatally exposed during that time are now reaching the age of increased breast cancer risk.

The researchers conducted a follow-up of 9,300 daughters of women who participated in the Child Health and Development Studies, which tracked Kaiser Foundation Health Plan members who received obstetric care in Alameda County, California from 1959 to 1967. The researchers studied 103 women who were diagnosed with breast cancer by age 52, and 315 controls matched by birth year.

Independent of the mother's history of breast cancer, elevated levels of the DDT isomer o,p'-DDT in the mother's blood were associated with a nearly fourfold increase in the daughter's risk of breast cancer (odds ratio for fourth quartile vs. first = 3.7, 95 percent; confidence interval = 1.5–9.0 ). Levels of o,p-DDT in fourth quartile participants were double or triple that of women in the first quartile. Among the women diagnosed with breast cancer, 83 percent had estrogen receptor positive breast cancer.

The authors point out that experimental studies are necessary to confirm these findings and to understand the mechanisms involved. If confirmed, this research could lead to biomarkers and interventions targeting DDT-associated breast cancer.

Citation Cohn BA, La Merrill M, Krigbaum NY, Yeh G, Park JS, Zimmermann L, Cirillo PM . DDT exposure in utero and breast cancer. J Clin Endocrinol Metab; doi:10.1210/jc.2015-1841 [Online 16 June 2015].

Cinnamon-derived compound helps prevent colon cancer in mice

Researchers, funded in part by NIEHS, showed that adding a compound found in cinnamon to the diet of mice protected against colorectal cancer. They also revealed new information about the role that nuclear factor-E2-related factor 2 (Nrf2) plays in the compound’s protective effects.

The Nrf2 molecular pathway is a master regulator of the cellular antioxidant defense, and thus plays a key role in protecting cells against stressors, such as carcinogen exposure and environmental damage. Cinnamon is a rich dietary source of cinnamaldehyde, which brings about an Nrf2-regulated antioxidant response in human epithelial colon cells.

In the new study, the researchers first used human colon epithelial cells to better understand the molecular mechanisms involved in Nrf2 activation. They found that cinnamaldehyde-induced Nrf2 activation was largely dependent on the status of Kelch-like ECH-associated protein 1 (Keap1)-Cys151. Keap-1 is a stabilizer of Nrf2 that, together with other molecules, promotes antioxidant pathways. The scientists also compared the protective potential of the compound in a mouse colorectal cancer model with Nrf2 and without Nrf2. When the mice received cinnamaldehyde supplementation, only those expressing Nrf2 showed colorectal cancer suppression, providing evidence that cinnamaldehyde’s protective effects depend on Nrf2.

Together, the new findings suggest that cinnamaldehyde, an FDA-approved food additive, may be a feasible way to suppress colorectal cancer. However, the researchers said that more studies are needed to determine the cinnamaldehyde dose needed for Nrf2 activation, and to test the feasibility of using cinnamon powder as a source of cinnamaldehyde for dietary cancer prevention.

Citation Long M, Tao S, Rojo de la Vega M, Jiang T, Wen Q, Park SL, Zhang DD, Wondrak GT . 2015. Nrf2-dependent suppression of azoxymethane/dextran sulfate sodium-induced colon carcinogenesis by the cinnamon-derived dietary factor cinnamaldehyde. Cancer Prev Res (Phila.) 8(5):444-454.

Paper devices quantify metals in aerosols

NIEHS grantees developed a simple technique that uses microfluidic paper-based devices to quantify concentrations of nickel, copper, and iron in airborne particulate matter. Commercial techniques typically cost more than $100 per sample and require trained specialists for operation, so low-cost approaches that are applicable at the point-of-need would greatly improve exposure assessment for particulate metals.

The researchers used paper substrates to create devices that can determine the amount of a substance of interest in only a drop of sample. Unlike other colorimetric approaches, the new technology does not require an external optical device for analysis. Instead, it relies on distance-based detection, which can be visually read much like the temperature on a thermometer.

The researchers demonstrated that the paper analytical devices can achieve detection limits as low as 0.1 micrograms for individual measurements of nickel and copper, and 0.05 micrograms for iron. When analyzing all three metals simultaneously, the devices showed a detection limit of 1 microgram for nickel and iron, and 5 micrograms for copper. They further tested the method by measuring the three metals in samples of certified welding fumes and found that the levels measured with the paper devices matched known values determined with gravimetric analysis.

Citation Cate DM, Noblitt SD, Volckens J, Henry CS. . 2015. Multiplexed paper analytical device for quantification of metals using distance-based detection. Lab Chip 15(13):2808-2818.

Lower leukemia risk associated with day care attendance or prolonged breastfeeding

Findings from a large pooled analysis reinforced the hypothesis that day-care center attendance in infancy and breastfeeding for at least six months are both associated with a decreased risk of acute lymphoblastic leukemia (ALL). ALL accounts for 80 percent of childhood acute leukemia, which is the most common cancer for children under 15 years old.

The researchers used data from 11 case-control studies participating in the Childhood Leukemia International Consortium to examine the association between ALL and early stimulation of the immune system. To do this, they looked at day care attendance, birth order, breastfeeding, and maternally reported common infections in infancy. The study included 7,399 ALL cases and 11,181 controls aged 2-14.

The researchers found that attending day care during the first year of life was associated with a reduced risk of ALL (odds ratio = 0.77, 95 percent confidence interval: 0.71, 0.84). The earlier a child began day care, the lower the risk of ALL (P < 0.0001). The researchers also observed a reduced risk associated with breastfeeding for 6 months or more (odds ratio = 0.86, 95 percent confidence interval: 0.79, 0.94).

Although early exposure to common infections may be responsible for the association with day care, there was no significant relationship between ALL and common infections in infancy. Understanding the potential mechanisms involved in this association requires assessing both the severity and the timing of infections.

Citation Rudant J, Lightfoot T, Urayama KY, Petridou E, Dockerty JD, Magnani C, Milne E, Spector LG, Ashton LJ, Dessypris N, Kang AY, Miller M, Rondelli R, Simpson J, Stiakaki E, Orsi L, Roman E, Metayer C, Infante-Rivard C, Clavel J . 2015. Childhood acute lymphoblastic leukemia and indicators of early immune stimulation: a Childhood Leukemia International Consortium study. Am J Epidemiol 181(8):549-562.

(Nancy Lamontagne is a science writer with MDB Inc., a contractor for the NIEHS Division of Extramural Research and Training.)

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