Grants - V Scholar Grants - Massachusetts - 2014

Andrew A. Lane, M.D., Ph.D.

Several common cancers occur more frequently in males than in females, but we do not understand why this is the case. It can’t be simply explained by differences in environmental exposures, like cigarette smoking.  Males have two different “sex chromosomes,” called X and Y.  Females have two copies of the X chromosome, but no Y.  Having XY (males) or XX (females) determines why males and females are different – they look different, make different hormones, and have different roles in passing genes to their children.  We think that the X and Y chromosome differences may also influence cancer risk, and explain why some cancers happen more frequently in men.

I am a hematologist/oncologist, and I take care of patients with blood cancers such as leukemia and lymphoma. We were studying blood cancers in the laboratory by sequencing cancer DNA from patients.  We found something very surprising: there was a group of patients with mutations in their DNA in a gene that “lives” on the X chromosome, and 100% of those patients were men.  We looked in the medical literature and found a few other examples of genes on chromosome X that were mutated in cancers that occur more often in men than women.

In this study, we will look at data from thousands of patients with many types of cancer to see if there is evidence for gene mutations on the X and Y chromosomes that explain some of the difference in cancer incidence between men and women. These findings may be relevant in the many cancers that are more frequent in men, including leukemia, myelodysplastic syndrome, kidney cancer, and bladder cancer. In addition, we will study these genes in the laboratory by deleting one copy in male cells, and one or two copies in female cells.  Together, these studies will determine how differences in mutations and number of copies of genes on the X chromosome contribute to cancer.  More broadly, we hope that by identifying and characterizing this new kind of cancer gene, we might also discover suggest new ways to prevent and/or treat these types of cancer.