BUFFALO, N.Y. -- Exposure to air pollution early in life and
when a woman gives birth to her first child may alter her DNA and
may be associated with premenopausal breast cancer later in life,
researchers at the University at Buffalo have shown.
The findings indicated that higher air pollution exposure at
birth may alter DNA methylation, which may increase levels of
E-cadherin, a protein important to the adhesion of cells, a
function that plays an essential role in maintaining a stable
cellular environment and assuring healthy tissues.
Methylation is a chemical process that has been implicated in
determining which genes in a cell are active, a process essential
to normal cellular function.
Women with breast cancer who lived in a region with more air
pollution were more likely to have the alteration in the DNA in
their tumor than those who lived in a less-polluted region, results
Higher air pollution concentration at the time of first child
birth also was associated with changes in p16, a gene involved in
tumor suppression, according to findings.
Results of the research were presented April 6 at the 2011
American Association for Cancer Research meeting in Orlando,
Lead investigator Katharine Dobson, MPH, an epidemiology
doctoral student and research assistant in UB's Department of
Social and Preventive Medicine, says of the findings: "To our
knowledge, this is the first study to examine exposure to ambient
air pollution at key points in a woman's lifetime.
"The investigation looked for an association between exposure to
pollution and alterations to DNA that influence the presence or
absence of key proteins. Such genetic changes are thought to be
major contributors to cancer development and progression, including
at very early stages," Dobson says.
The study is based on data from the Western New York Exposures
and Breast Cancer (WEB) study, which collected information from
1,170 women with recently diagnosed breast cancer and 2,116 healthy
women who lived in New York's Erie and Niagara counties between
1996 and 2001. This research involved only cancer cases.
Participants provided information on where they were born, where
they lived at the time of their first menstrual period, and, if
they had children, where they lived when they bore their first
child. Data from air monitors operating in the relevant time
periods was used to determine the amount of particulate matter at
each participant's residence at those time periods. Air pollution
data from 87 sites in Western New York was matched with residence
location at year of birth, year of menarche and year of first child
"We found that decreased E-cadherin promoter methylation was
associated with higher exposure at birth, and increased p16
methylation with higher exposure at the time of a first child
birth," says Dobson.
"For breast cancer cases, menopausal status appeared to modify
the association between air pollution exposure and E-cadherin
promoter methylation, with premenopausal women more susceptible to
these early exposures than postmenopausal women."
More research is needed to determine the role of air pollution
in DNA methylation in breast cancer development and progression,
and to address changing air pollution contents and levels over
time, Dobson notes
Jo L. Freudenheim, PhD; Menghua Tao, MD, PhD; Jing Nie, PhD; and
Matthew Bonner, PhD, all from UB, contributed to the study, as well
as researchers from Lombardi Comprehensive Cancer Center,
Georgetown University, Washington D.C.; Roswell Park Cancer
Institute, Buffalo, N.Y.; Potomac Hospital, Woodbridge, Va.; and
University of Nevada Health Sciences System, Las Vegas, Nev.
The study was funded by the National Cancer Institute.
The University at Buffalo is a premier research-intensive public
university, a flagship institution in the State University of New
York system and its largest and most comprehensive campus. UB's
more than 28,000 students pursue their academic interests through
more than 300 undergraduate, graduate and professional degree
programs. Founded in 1846, the University at Buffalo is a member of
the Association of American Universities.