Featured Research

from universities, journals, and other organizations

Excess estrogen in pregnancy can silence BRCA1 in daughters, increasing breast cancer risk

Date:
April 9, 2013
Source:
Georgetown University Medical Center
Summary:
Excess estrogen levels during pregnancy can disable, in their daughters, a powerful breast cancer tumor suppressor gene, say researchers. They found the DNA repair gene BRCA1 to be silenced in one year-old girls exposed to a high hormonal fetal environment.

Excess estrogen levels during pregnancy can disable, in their daughters, a powerful breast cancer tumor suppressor gene, say researchers at Georgetown Lombardi Comprehensive Cancer Center. They found the DNA repair gene BRCA1 to be silenced in one year-old girls exposed to a high hormonal fetal environment.

Related Articles


The researchers say their study, presented at the AACR Annual Meeting 2013, suggests that BRCA1 silencing by methylation in utero may be an important mechanism that increases breast cancer risk later in life. And they say that, if confirmed, there could be ways of lowering that risk before breast cancer develops.

"We may be able to identify women at increased risk of developing breast cancer by looking for BRCA1 that has been methylated as a marker of having been exposed to excess estrogen levels in utero," says the study's lead author, Leena Hilakivi-Clarke, PhD, a professor of oncology at Georgetown Lombardi.

Not only was BRCA1 silenced by methylation in the one-year-old girls who developed in a highly estrogenic fetal environment, there were other molecular abnormalities that can contribute to breast cancer risk and risk of breast cancer recurrence, says Hilakivi-Clarke.

For the study, the researchers compared the gene DNA methylation profiles of the daughters to publicly available databases collected from a large number of breast cancer patients in the Cancer Genome Atlas (TCGA). They found that those genes with altered methylation in the daughters of women with the highest pregnancy estradiol levels are also differentially methylated in breast cancer patients.

In addition to BRCA1, another gene abnormality found was in the unfolded protein response (UPR) pathway, which has been linked to breast cancer risk and resistance to tamoxifen, a treatment for breast cancer.

Researchers at Virginia Tech, who collaborated with Hilakivi-Clarke on this study, found that the UPR pathway was "hypomethylated" (genes were turned on or highly active), in the one-year old daughters. They further confirmed that the same UPR genes also were hypomethylated in breast cancers in women, compared to normal breast tissue, as well as in breast cancer cells that are resistant to tamoxifen treatment, compared to tamoxifen sensitive breast cancer cells.

"When these UPR genes are activated it means that damaged cells that should die do not, increasing the risk that cancer develops, and that cancer cells do not respond to treatment," says study collaborator, Robert Clarke, DSc, dean for research at Georgetown University Medical Center.

"Given these findings, perhaps we can identify those breast cancer patients who develop resistance to hormonal therapy and are at high risk of recurrence," Hilakivi-Clarke says. "Because several drugs are now available to reverse an increase in gene methylation, it may be possible to reverse the increase in breast cancer risk and prevent development of resistance to tamoxifen in these women."

"It does not matter how BRCA1 is eliminated -- by mutation or epigenetic silencing -- the end result is the same: there is less BRCA1 to defend the cells from becoming cancerous," she says.

In addition to Hilakivi-Clarke and Clarke, authors include Riitta Luoto of the UKK Institute in Tampere, Finland; Xiao Zhang and Jason Xuan of Virginia Tech; and Nguyen Nguyen, Xiyuan Zhang, Jin Lu, and Alan Zwart of Georgetown Lombardi.

U.S. funding for this research was provided by the National Cancer Institute (U54 1U54CA149147 and 1R01CA164384). Funding was also provided by Pirkanmaa Hospital, Academy of Finland, and Ministry of Education and Culture of Finland. Hilakivi-Clarke reports having no personal financial interests related to the study.


Story Source:

The above story is based on materials provided by Georgetown University Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

Georgetown University Medical Center. "Excess estrogen in pregnancy can silence BRCA1 in daughters, increasing breast cancer risk." ScienceDaily. ScienceDaily, 9 April 2013. <www.sciencedaily.com/releases/2013/04/130409144839.htm>.
Georgetown University Medical Center. (2013, April 9). Excess estrogen in pregnancy can silence BRCA1 in daughters, increasing breast cancer risk. ScienceDaily. Retrieved December 18, 2014 from www.sciencedaily.com/releases/2013/04/130409144839.htm
Georgetown University Medical Center. "Excess estrogen in pregnancy can silence BRCA1 in daughters, increasing breast cancer risk." ScienceDaily. www.sciencedaily.com/releases/2013/04/130409144839.htm (accessed December 18, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Thursday, December 18, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Kids Die While Under Protective Services

Kids Die While Under Protective Services

AP (Dec. 18, 2014) As part of a six-month investigation of child maltreatment deaths, the AP found that hundreds of deaths from horrific abuse and neglect could have been prevented. AP's Haven Daley reports. (Dec. 18) Video provided by AP
Powered by NewsLook.com
Dads-To-Be Also Experience Hormone Changes During Pregnancy

Dads-To-Be Also Experience Hormone Changes During Pregnancy

Newsy (Dec. 18, 2014) A study from University of Michigan researchers found that expectant fathers see a decrease in testosterone as the baby's birth draws near. Video provided by Newsy
Powered by NewsLook.com
Prenatal Exposure To Pollution Might Increase Autism Risk

Prenatal Exposure To Pollution Might Increase Autism Risk

Newsy (Dec. 18, 2014) Harvard researchers found children whose mothers were exposed to high pollution levels in the third trimester were twice as likely to develop autism. Video provided by Newsy
Powered by NewsLook.com
UN: Up to One Million Facing Hunger in Ebola-Hit Countries

UN: Up to One Million Facing Hunger in Ebola-Hit Countries

AFP (Dec. 17, 2014) Border closures, quarantines and crop losses in West African nations battling the Ebola virus could lead to as many as one million people going hungry, UN food agencies said on Wednesday. Duration: 00:52 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins