An international group of researchers has discovered a new phenomenon that occurs in identical twins: independent of their identical genes, they share an additional level of molecular similarity that influences their biological characteristics. The reasearch results were appeared in the journal Genome Biology. The researchers propose a mechanism to explain the extra level of similarity and show that it is associated with risk of cancer in adulthood.

"The characteristics of an individual depend not only on genes inherited from the parents but also on epigenetics, which refers to molecular mechanisms that determine which genes will be turned on or off in different cell types. If we view one's DNA as the computer hardware, epigenetics is the software that determines what the computer can do," said senior author Dr. Robert A. Waterland,

Epigenetics works by adding or removing chemical tags to genes to mark which ones should be used in different cell types. One of the better studied tags, known to play an important role in development and cancer, is the methyl chemical group. Here, in a large group of identical and fraternal twin pairs, Waterland and his colleagues studied a group of genes called metastable epialleles.

Identical twins are formed when the very early embryo essentially a ball of cells splits into two parts, and each continues to develop into a separate human being. The authors proposed and tested a simple model to explain epigenetic supersimilarity.

"If, in this group of genes, the epigenetic markers are established before the embryo splits into two, then the markers will be the same in both twins," Waterland said. "In essence, both twins inherit an intimate molecular memory of their shared developmental legacy as a single individual. On the other hand, genes at which epigenetic markers are set after the embryo splits can have greater epigenetic differences between the two twins."

Cancer connection

Epigenetic supersimilarity seems to occur in a relatively small group of genes, but, as the researchers discovered, many of these are associated with cancer. To test whether these epigenetic markers might affect risk of cancer, the scientists in Houston teamed up with cancer epidemiologists running the Cancer Council Victoria's Melbourne Collaborative Cohort Study in Melbourne, Australia. Back in the 1990s, this large study was set up to assess different risk factors for cancer.

"By analyzing peripheral blood DNA samples from healthy adults in our study, we have been able to show that methylation at epigenetically supersimilar genes is associated with risk of subsequently developing several types of cancer, including lung, prostate and colorectal cancer," said Dr. Roger Milne, an author on the study.

"Our findings should prompt a re-evaluation of previous genetic studies on twins," Waterland said. "For decades, researchers have studied genetically identical twins to estimate what proportion of disease risk is determined by one's genes. To the extent that epigenetic supersimilarity affects risk of disease, as our results indicate, genetic risk estimates based on twin studies have been inflated."