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Developmental biology - Ancestral Genes

Ancestor Genes May Trigger Breast Cancer

Threat of malaria left its mark on our immune system...


Threat of malaria left its mark in people with African ancestry researchers discover and publish in the journal PLOS Genetics. In the new study published June 7th, 2018, Christine Ambrosone of Roswell Park Comprehensive Cancer Center, and colleagues, identified a genetic difference between African and European ancestry which triggers unique immune inflammation responses. Researchers suspect this gene became rooted in our immune systems as people acclamated to malaria while living in Africa.

Our immune system continually evolves to fight off the constant threat of local infectious agents, tailoring its response to routine assaults. Thanks to modern hygiene, we now faces far fewer attacks, but ancestral gene differences remain within our genomes, demonstrated by differing disease rates between populations.

Malaria amongst red blood cells

Malaria amongst red blood cells

To better understand how different immune systems respond to current lifestyles, researchers combined genetic, molecular and epidemiological data from 914 people of African ancestry and compared that data to 855 people with European ancestry. The data originated from the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium.
Researchers analyzed the AMBER blood samples and detected 14 different chemical messengers which initiate or support inflammation, identifying significant differences between the 2 groups in seven of those chemical messengers.

Lifestyle factors such as age, level of education, obesity, smoking and alcohol use — account for many of these. But, researchers also identified a genetic variant that occurred primarily in people of African ancestry. This variant controls the level of two key chemical messengers which recruit white blood cells to inflammation sites. Previous studies suggested chemical messengers evolved to protect Africans from contracting malaria. But, verification of this idea suggests other health issues may deserve follow up.
Inflammation is a response to injury and infection but, is also implicated in several types of cancer and chronic disease. Ancestral footprints such as malaria, may exist in other human groups.

Researchers based their research upon the hypothesis that viral adaptation over millennia protected people from infectious diseases — but may also stimulate a more more aggressive breast cancer in our modern environment.
"When we compared levels of certain inflammatory markers between women of African and European descent, we noted many differences. After we ruled out the effects of lifestyle factors, we found that much of these differences could be tied to the Duffy antigen receptor a genotype that helps protect from malaria."

"These findings indicate evolutionary adaptation many thousands of years ago shaped our immune systems, and may still have considerable influences on immune function today. The next research question we are pursuing is whether those evolutionary marks play any significant role in affecting breast cancer disparities."


Song Yao PhD, Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA and first author.

Abstract
Selection pressure due to exposure to infectious pathogens endemic to Africa may explain distinct genetic variations in immune response genes. However, the impact of those genetic variations on human immunity remains understudied, especially within the context of modern lifestyles and living environments, which are drastically different from early humans in sub Saharan Africa. There are few data on population differences in constitutional immune environment, where genetic ancestry and environment are likely two primary sources of variation. In a study integrating genetic, molecular and epidemiologic data, we examined population differences in plasma levels of 14 cytokines involved in innate and adaptive immunity, including those implicated in chronic inflammation, and possible contributing factors to such differences, in 914 AA and 855 EA women. We observed significant differences in 7 cytokines, including higher plasma levels of CCL2, CCL11, IL4 and IL10 in EAs and higher levels of IL1RA and IFN?2 in AAs. Analyses of a wide range of demographic and lifestyle factors showed significant impact, with age, education level, obesity, smoking, and alcohol intake, accounting for some, but not all, observed population differences for the cytokines examined. Levels of two pro-inflammatory chemokines, CCL2 and CCL11, were strongly associated with percent of African ancestry among AAs. Through admixture mapping, the signal was pinpointed to local ancestry at 1q23, with fine-mapping analysis refined to the Duffy-null allele of rs2814778. In AA women, this variant was a major determinant of systemic levels of CCL2 (p = 1.1e-58) and CCL11 (p = 2.2e-110), accounting for 19% and 40% of the phenotypic variance, respectively. Our data reveal strong ancestral footprints in inflammatory chemokine regulation. The Duffy-null allele may indicate a loss of the buffering function for chemokine levels. The substantial immune differences by ancestry may have broad implications to health disparities between AA and EA populations.

Authors: Citation: Yao S, Hong C-C, Ruiz-Narváez EA, Evans SS, Zhu Q, Schaefer BA, et al. (2018) Genetic ancestry and population differences in levels of inflammatory cytokines in women: Role for evolutionary selection and environmental factors. PLoS Genetics. Other authors: Deborah Karasek, Kristina Dang and Paula Braveman of UC San Francisco, Elizabeth Ogburn of the Johns Hopkins University Bloomberg School of Public Health in Baltimore and Dana Goin of UC Berkeley.

Competing Interests: The authors have declared that no competing interests exist.

Acknowledgements
Funding: This work was supported by the National Cancer Institute (grant number P01CA151135 to C.B.A, J.R.P., and A.F.O, R01CA058420 to L.R., UM1CA164974 to L.R., R01CA098663 to J.R.P., R01CA100598 to C.B.A., P50CA58223 to M.A.T. and A.F.O.); the University Cancer Research Fund of North Carolina (M.A.T. and A.F.O.); and the Breast Cancer Research Foundation (C.B.A.). Roswell Park Cancer Institute (RPCI) Data Bank and Biorepository and the Flow Cytometry Shared Resource are Cancer Center Support Grant (CCSG) Shared Resource supported by the National Cancer Institute (grant number P30CA16056 to Johnson CS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Jun 13, 2018   Fetal Timeline   Maternal Timeline   News   News Archive




African American/Black women under the age of 40 have more aggressive and deadly tumors, need earlier, more frequent breast cancer screenings, and aggressive medical treatment to increase their survival advantages. African American Breast Cancer Alliance. Image: Public Domain.


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