With support from UC Davis, GSK Oncology, and V Foundation grants, we are working to identify new genes associated with breast cancer. Plans are in place to validate relevancy of the discoveries through partnerships with other investigators at UC Davis, Stanford, UCSF, University of Southern California, and the Cancer Prevention Institute of California. Our work has already revealed interesting background on the history and ancestry of these villagers.

Studies of maternal lines through mitochondrial DNA as it is passed from mothers to children have shown that ancestral mothers were primarily Native American. More surprising is the paternal lineage. Our testing in men found that almost all the genetic makeup of the Y chromosome DNA is European in origin.

It is likely that male Spanish conquistadors settled in the area, taking Native American women as wives. The male Native American population was presumably decimated from disease and conflict. Few European women came to the area, so the European men married the remaining Native American women, each passing on their genetic lines. These findings are among the most striking examples of male-driven directional mating in humans and have been subsequently replicated by many researchers in other Hispanic populations.

The homogeneity of these Andean villagers means there are large families with the same cancers caused by very few mutations passed down by village ancestors. We have screened 191 women with breast cancer in Colombia and identified 25 patients and families with the same genetic mutation in the BRCA1 gene. Genealogical studies indicate the mutation was likely introduced by a Spanish ancestor who settled in the Huila Province and whose descendants still live in the region. We are now using modern genome sequencing methods to identify mutations in new genes as we expect that many more “founder mutations” are still undiscovered and will give us clues about genetic susceptibility to cancer and its biology.