Papers of the Month
By Robin Arnette, Ernie Hood, Prashant Rai, Saniya Rattan, and Nancy Urbano
Study finds eating processed meat increases colorectal cancer risk in women
Scientists from the Division of the National Toxicology Program and the NIEHS intramural program reported that increased intake of processed meat and use of high temperature to cook red meats increased the risk of colorectal cancer in women. This study supported previous hazard assessments on processed meat and added information on colorectal cancer (CRC) risks associated with specific processed meat products and cooking practices.
Among 48,704 women in the Sister Study, followed for a median of 8.7 years, 216 developed CRC. Women in the highest quartile of processed meat consumption had a 50% increase in risk of CRC compared to women in the lowest quartile. Bacon was found to be associated with the highest risk of getting CRC, with a twofold increase in risk, followed by consumption of breakfast sausages. In terms of cooking practices reported for steaks and burgers, grilling/barbequing was associated with elevated risk of cancer.
Nitrates and nitrites used in curing processed meats are known to be mutagenic. Use of high heat and direct flame while cooking red meat may lead to formation of hydrocarbons, which can also increase chances of cancer-forming mutations. Information on associations between specific dietary factors and cancer risk may aid in CRC prevention. (PR)
Citation: Mehta SS, Arroyave WD, Lunn RM, Park YM, Boyd WA, Sandler DP. 2019. A prospective analysis of red and processed meat consumption and risk of colorectal cancer in women. Cancer Epidemiol Biomarkers Prev; doi: 10.1158/1055-9965.EPI-19-0459 [Online 1 October 2019].
Double-strand break repairs may lead to cancerous mutational clusters
Using a method called mutation cluster analysis, NIEHS scientists and their collaborators showed that bursts of double-strand breaks (DSBs) can lead to non-random clustered mutations in yeast and human cancers. They identified three potential sources that enable cluster formation associated with repairing bursts of DSBs: 5' to 3' bidirectional resection, unidirectional resection, and break-induced replication (BIR). They concluded that a BIR-like mechanism is most responsible for cluster formation in cancers.
The scientists generated multiple simultaneous DSBs scattered throughout the yeast genome in the presence of a single-strand, DNA-specific apolipoprotein-B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) cytosine deaminase. This approach allowed them to determine whether the yeast genome could withstand multiple stretches of single-strand DNA, which could lead to many mutations. They used more than 10,000 mutation clusters in cancers with high APOBEC mutagenesis.
In addition to finding the three independent sources of single-strand DNA that produce clustered mutations, the researchers found that bursts of DSBs can happen in clustered mutations that occurred in a single cell. This work adds to a basic understanding of the molecular origins of carcinogenesis. (EH)
Citation: Sakofsky C, Saini N, Klimczak LJ, Chan K, Malc EP, Mieczkowski PA, Burkholder AB, Fargo D, Gordenin DA. 2019. Repair of multiple simultaneous double-strand breaks causes bursts of genome-wide clustered hypermutation. PLoS Biol 17(9):e30000464. (Story)
Study finds possible association between talc and uterine cancer
Using data from 33,609 women enrolled in the Sister Study, NIEHS scientists saw a positive association between genital talc use and the risk of uterine cancer. The researchers found the association was stronger among women who reported frequent talc use, compared to those who never used talc or only applied it sometimes. Team members said the findings do not mean that talc use causes uterine cancer but noted the result was consistent with other studies that observed an association between talc use and elevated incidence of uterine cancer. The researchers stressed that more comprehensive studies are needed to confirm the association. They did not observe an association between douching and risk of uterine cancer.
At enrollment, participants completed a self-reported questionnaire about their use of a wide range of personal care products, including douche and talcum powder applied to the genital area. The questionnaire did not ask about specific brand name products but asked whether the women used these products in the 12 months prior to enrollment and when they were aged 10-13 years. Twenty-six percent of the women in the study reported ever using talc in their genital area and 15% reported they had ever douched. During the average follow-up period of 8 years, 271 participants developed uterine cancer. (NU)
Citation: O’Brien KM, D’Aloisio AA, Shi M, Murphy JD, Sandler DP, Weinberg CR. 2019. Perineal talc use, douching and the risk of uterine cancer. Epidemiology 30(6):845−852.
Geographically specific air pollution associated with breast cancer
NIEHS researchers, along with collaborators, observed an association between residential exposure to air pollution and breast cancer risk, which varied based on geographic region and the composition of the air pollution particles. They found that air pollution was associated with the risk of both invasive breast cancer and ductal carcinoma in situ. This new research suggested that variability in air pollution composition could explain differences across studies that evaluated the association between particulate matter (PM) and breast cancer.
Sister Study participants provided information on their residence at time of enrollment, as well as demographic and lifestyle factors. They were followed for breast cancer over an average of 8 years. The researchers estimated residential exposure to PM less than 2.5 micrometers, PM less than 10 micrometers, and nitrogen dioxide. PM is a complex mixture of different types of particles, and these patterns vary geographically. Among women in the western U.S. and with certain patterns of PM composition, greater exposure to air pollution was associated with higher risk of breast cancer. These results emphasize the importance of continued reduction in air pollution levels. (SR)
Citation: White AJ, Keller JP, Zhao S, Carroll R, Kaufman JD, Sandler DP. 2019. Air pollution, clustering of particulate matter components, and breast cancer in the Sister Study: a U.S.-wide cohort. Environ Health Perspect 127(10):107002.
Estrogen made by fat in overweight girls does not cause early puberty
Research led by NIEHS scientists and their collaborators dispelled the notion that overweight girls undergo puberty earlier than normal weight girls because of estrogen made by excess fat tissue. The work helps researchers, clinicians, and parents better understand how body weight affects puberty in girls.
The ovaries produce estrogen, which induces breast development in girls. Fat tissue can also produce small amounts of estrogen. Other researchers proposed that overweight girls may develop breasts earlier than normal weight girls because of estrogen made by fat tissue within the breast or other parts of the body. The research team enrolled 54 normal weight girls and 26 overweight girls and measured percent body fat using dual energy x-ray absorptiometry, determined amount of breast tissue using breast ultrasound, and measured blood estrogen levels using mass spectrometry.
The team found no difference in blood estrogen levels between the two groups, which suggested that earlier breast development in overweight girls is not due to estrogen made by excess fat. Instead, the brain region that controls puberty may turn on earlier in overweight girls. The girls in the study are being followed for 2-3 years to see how body weight affects the timing and pace of puberty. (RA)
Citation: Carlson L, Flores Poccia V, Sun BZ, Mosley B, Kirste I, Rice A, Sridhar R, Kangarloo T, Vesper HW, Duke L, Botelho JC, Filie AC, Adams JM, Shaw ND. 2019. Early breast development in overweight girls: does estrogen made by adipose tissue play a role? Int J Obes (Lond) 43(10):1978−1987. (Story)
(Ernie Hood is a contract writer for the NIEHS Office of Communications and Public Liaison. Prashant Rai, Ph.D., is a visiting fellow in the NIEHS Clinical Investigation of Host Defense Group. Saniya Rattan, Ph.D., is an Intramural Research Training Award [IRTA] fellow in the NIEHS Reproductive Developmental Biology Group. Nancy Urbano is an IRTA postbaccalaureate fellow in the Predictive Toxicology and Screening Group of the National Toxicology Program.)