Environmental and dietary influences on cancer risk
Studies show how exposure to environmental carcinogens causes dna damage in smokers, women and their unborn children
ORLANDO – Genetic damage triggered by environmental carcinogens, including smoking, is being further defined with the aid of new technology, including microarrays, polymorphisms and DNA adducts, one of the first steps in the carcinogen pathway that ultimately leads to tumor formation. In this press briefing at the 95th Annual Meeting of the American Association for Cancer Research, scientists report their findings of specific DNA damage resulting from combustion and smoking-related carcinogens, and in the case of two studies, the impact of prenatal exposures on unborn children.
Levels of Polycyclic Aromatic Hydrocarbons in Amniotic Fluid Samples from Smokers and Nonsmokers: Abstract No. 3189
The amniotic fluid of smoking women in their first trimester of pregnancy contains about 10 times the amount of a known tobacco carcinogen -- polynuclear aromatic hydrocarbons (PAHs) – than nonsmokers. Similar results were found for another established cancer-causing agent, known as benzo(a)pyrenes.
"This is the first study to show the presence of carcinogens in the fetus at this early stage of development," said Steven R. Myers, Ph.D., Director of the Center for Environmental and Occupational Health Sciences at the University of Louisville School of Medicine and lead author of the study.
In all, more than 500 women participated in the study, which involved routine amniocentesis performed between 16 to 20 weeks of pregnancy. The first trimester is a particularly critical period for the developing fetus, during which rapid cell division and growth takes place. Amniotic fluid not only helps protect and cushion the fetus, it also plays an important role in the development of many fetal organs, including the lungs, kidneys and gastrointestinal tract.
"There is a great potential at this time for severe DNA damage and potential alterations in genes that may predispose the child to later cancers," said Myers. "Any compounds that have potential to disrupt these processes such as chemical carcinogens found in tobacco are detrimental."
Scientists analyzed fluid extracted from nonsmokers and smokers, ranging from a half-pack to more than two packs per day. Levels of PAHs were detected in virtually all amniotic samples. However, there was a clear correlation between smoking and high concentrations of PAHs and benzo(a)pyrenes that passed from the mother's circulatory system across the placenta and into the amniotic fluid. Levels range from about 1.5 micrograms per liter in nonsmokers to about 11.7 in women who smoked more than two packs per day, about a 10-fold increase.
Myers added that his group is now following the growth curves of these children, in addition to other short-term outcomes, including respiratory and cognitive function.
Comparison of Polycyclic Aromatic Hydrocarbon (PAH)-DNA Adducts in Four Populations of Mothers and Newborns in the U.S., Poland and China: Abstract No. 1975
Prenatal exposure to combustion-related pollutants found in the urban air in the United States, Poland and China results in genetic damage that has been linked to increased cancer risk. The research provides molecular evidence that the fetus is more susceptible to DNA damage than the mother.
According to a new study of mothers and their newborns, even low levels of carcinogenic polycyclic aromatic hydrocarbons (PAHs) are damaging the DNA of fetuses in the womb. The type of DNA damage measured here (termed "carcinogen-DNA adducts") has been shown to increase the risk of cancer in humans.
Four population groups were selected for the study, including mothers and their newborns from two sites in New York City (Northern Manhattan and the World Trade Center area); Krakow, Poland; and Tongliang, China. In all, carcinogen-DNA adducts were analyzed in cord blood from 822 newborns and blood samples collected at delivery from 867 women.
"This study suggests that even small exposures to the pollutants pose some risk to the fetus and supports preventive policies to limit exposures of pregnant women and children," said Frederica P. Perera, Dr.P.H., professor of public health and director of the Columbia Center for Children's Environmental Health at the Mailman School, Columbia University. "The evidence that the fetus is more susceptible than the mother to DNA damage underscores the need for prevention."
The populations were selected to represent the range of environmental exposure to air pollutants worldwide and, in the case of the World Trade Center study, to learn about possible risks from that unprecedented event. Available air monitoring data from the three cities indicate that the average levels of benzo[a]pyrene, a representative PAH, ranged from a low of 0.5 nanograms per cubic meter in New York City to greater than 15 nanograms per cubic centimeter in Tongliang, about a 30-fold range. Mean adduct concentrations in cord blood increased across the populations, consistent with the trend in ambient exposure to PAHs.
Levels of DNA damage, or adducts, seen among newborns from Northern Manhattan and the World Trade Center population were significantly lower than in either the Polish or Chinese newborns. The study suggested that the fetus may be as much as 10 times more susceptible to DNA damage than the mother. Despite the estimated 10-fold lower PAH dose to the fetus, the adduct levels in the newborns were similar to or higher than in the mother.
The alcohol dehydrogenase 3 polymorphism is associated with an increased alcohol/tobacco-associated risk of oral and pharyngeal carcinomas: Abstract No. 3975
Scientists have identified a genetic variant that places heavy drinkers who smoke at a much higher risk of oral cancer than their counterparts.
According to a Boston-based study, heavy alcohol consumption accompanied by smoking resulted in a 12-fold higher risk of head and neck squamous cell cancer among this population group.
"These findings provide clear evidence that, at least in this case, consideration of the interaction between smoking and drinking can be critical for assessing and accurately estimating the magnitude of genetic susceptibility to HNSCC," said Edward S. Peters, D.M.D., Sc.D., at the Harvard School of Public Health and Brigham and Women's Hospital in Boston, and lead author of the study.
The scientists analyzed the genetic makeup of 520 individuals in the Boston area with confirmed cases of HNSCC, along with 597 controls. Specifically, the team homed in on variants of a gene known as ADH3.
Alcohol is eliminated through oxidation, first to acetaldehyde -- a suspected oral carcinogen -- with the aid of a catalyst known as alcohol dehydrogenase, or ADH.
The ADH3 gene, which helps encode ADH, comes in several forms, or is polymorphic. The ADH3*1 form is capable of metabolizing ethanol to acetaldehyde at a higher rate than its sibling, the ADH3*2 allele.
In a preliminary analysis, the scientists found that approximately 40 percent of those individuals with head and neck cancer carried the homozygous ADH3*1 genotype, while one-third of the controls shared this genetic characteristic. For the remaining part of the group, 46 percent and 47 percent were heterozygous, while 14 percent and 15 percent were ADH3*2.
Examination revealed that heavy drinking increased the risk of oral cancer by a factor of 5 among individuals who inherited both copies of the ADH3*2 gene, compared to a 3-fold higher risk among ADH3*1 polymorphism.
However, since the interaction of smoking and drinking has been linked in previous studies to increased risk of HNSCC, the scientists sought to determine how this interaction would influence the ADH3 polymorphism.
Smoking and drinking together conferred a 12-fold increase in risk for oral cancer among the ADH3*2 homozygous variant population, compared to a 6-fold increase among the ADH3*1 homozygous wildtype or heterozygous ADH3 individuals.
"These findings suggest that the ADH3 variant allele is associated with susceptibility to smoking/drinking-related HNSCC," said Peters.
Source: Eurekalert & othersLast reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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