Low-level cadmium exposure can increase female cancer risk ...

Hossain, MB, M Vahter, G Concha and K Broberg, 2012. Low-level environmental cadmium exposure is associated with DNA hypomethylation in Argentinean women. Environmental Health Perspectives.

Women exposed to low levels of cadmium in their food have changes in DNA markers that alter gene regulation and increase their cancer risk. This study for the first time suggests that cadmium may be turning genes on or off in a way that triggers disease.

A recent study suggests a new understanding of the way long-term cadmium exposure from a women's diet can increase her risk for cancer.

Cadmium levels in the blood of women from Argentina were linked to changes in how the DNA in cells is tagged or marked by a methyl group, a process that can alter the way the genes are read and expressed. The decreased number of DNA markers associated with cadmium exposures in the women resemble genes commonly found in cancer cells and not normal cells.

While cadmium is long associated with higher cancer risk and some illnesses, how it exerts its effects is still not clear. Lab studies indicate cadmium can alter DNA tags, or DNA methylation. This study is important because it is the first to report this type of epigenetic effect of cadmium exposure in people. It offers a possible mechanism for the metal's link to cancer.

DNA methylation occurs when a chemical group called a methyl group is added onto DNA. This mark does not change the actual sequence of the DNA, but rather is a kind of go/stop signal that affects whether a particular gene is expressed or not. Changes in DNA tags can lead to cancer and other diseases. The methylation changes can be inherited if they are incorporated into the egg, sperm or other germ cells that give rise to them.

Cadmium is a heavy metal used in batteries, pigments and metal plating and is a by-product of ore smelting. Once in the environment, it does not disappear. People are exposed through diet, air pollution and smoking. Plants - including some of the crops we eat - absorb cadmium from fertilizers and contaminated soil. Major dietary sources are whole grains, potatoes, vegetables and shellfish. Burning of fossil fuels releases cadmium and increases levels in air pollution.

Cadmium is toxic and can act like an estrogen, increasing the risk for hormone related cancers such as breast cancer. Women whose diets contained higher levels of cadmium have a greater risk of developing breast cancer. Cadmium exposure is also associated with kidney disease, bone softening and impairment of early life development.

The researchers followed a group of 202 Argentinian women who live in the Andean plateau, a region that has minimal industrial pollution and low vehicle traffic. Cadmium exposure is primarily from diet. The Swedish researchers measured cadmium in the women's blood, which represents ongoing cadmium exposure, and in their urine, which represents life-long exposure. They calculated the levels of genes responsible for attaching the methyl groups to the DNA and counted the number of DNA tags in specific locations along the DNA of blood cells.

The author's compared the amount of cadmium in the blood and the urine to the amount of methylation on the DNA and the gene expression levels. They adjusted for factors that might interfere with the results, such as age and coco chewing.

The women had lower cadmium levels (0.23 micrograms per liter (?g/L)) than women in the U.S. population (0.4 ?g/L). The more cadmium found in the urine, the lower the amount of methylation on the DNA segments examined. The association was stronger in a subset of the women with a certain genetic mutation in a gene that maintains DNA methylation. Another gene responsible for placing the methyl markers was expressed at a lower level in women with high cadmium levels.

Together, these results suggest that life-long exposure to cadmium affects the process of DNA methylation.

Cadmium levels within the blood were not strongly correlated to any of these changes suggesting that long-term, low-level exposure is potentially more detrimental than the current levels in the blood.

One drawback of this study is that it is based on a relatively small population of women who were not exposed to cadmium through pollution. These findings will need to be repeated in larger, more diverse populations. Future studies are necessary to confirm these findings in other tissues and if these changes in DNA structure plays a role in other cadmium-related diseases.

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