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Testing lets would-be parents breathe easier

By Dr. V. Upender Rao
Published December 18, 2006

In the past several years, mortality rates for patients with many common cancers have been steadily improving. Improved techniques in anesthesia, surgery, postoperative care and radiation therapy have all contributed. The most dramatic discoveries, however, have emerged in the broad-based field of hematology and oncology.

Since the decoding of the human genome, it has become increasingly possible to compare the molecular footprints of tumors with that of the native, normal tissue where they evolve. Deviations from normal are identified and marked as targets for drug development. Several such targeted drugs are already being used in clinical oncology.

Preventive measures also play a pivotal role in the incidence of cancer. Mammography, colonoscopy and Pap smears are classified as "secondary prevention" because they do not actually prevent cancer but facilitate early diagnosis at a curable stage.

Never smoking might be considered "primary prevention" for most lung cancers (except for the newly recognized entity of bronchoalveolar cancer in non-smoking women with epidermal growth factor receptor mutation) because a smoke-free lung may not be conducive for the initiation of tumorigenesis.

In the Dec. 13 issue of the Journal of the American Medical Association, researchers from the Memorial Sloan-Kettering Cancer Center in New York present information on a dramatic possibility of preventing cancer even before the embryo is implanted in the uterus for gestation.

This process of selecting embryos that are free of cancer-related mutations is known as preimplantation genetic diagnosis, or PGD.

In this procedure, DNA from one or two single cells in the pre-embryo stage is extracted for analysis. There are only six to eight such cells. A DNA-analyzed cell that is devoid of any cancer-related mutation is transferred to the uterus, and those that harbor mutations can be withheld.

With this strategy, cancer and other genetically inherited diseases can be avoided.

More 7,000 PGD cycles have been performed worldwide, resulting in 1,000 live births. This procedure is expected to increase as hundreds of U.S. and international in vitro fertilization centers master this technique and gain access to labs that can perform single-cell DNA analysis.

PGD has been performed for several dominantly inherited cancer-predisposing syndromes, including colorectal, breast and ovarian cancer, as well as the less-common recessive syndromes that predispose to leukemia and lymphoma.

If proved to be consistently safe, this technique would be an important tool that would help avoid cancer and other lethal diseases in high-risk families. On the other hand, there is a high possibility of abuse of this procedure to select the birth of perfect humans or inducing traits of intellectual, physical, athletic and cosmetic excellence.

The American Medical Association's code of ethics accepts prenatal genetic testing where medical histories or family background indicates an elevated risk for fetal genetic disorders. International ethics societies have favored supporting assisted reproductive technology for defined medical indications. The U.S. President's Council on Bioethics emphasizes the documentation of the safety of these procedures.

Individuals have emphasized ethics and personal considerations, such as the nature of the trait or disease being avoided by this technique (whether or not it constitutes a severe and life-threatening disease).

To address this issue, scientists developed pre-embryonic testing of the "polar body" DNA. Polar bodies are the product of the division of the oocyte. On division, one cell becomes the ovum or egg and the rest become polar bodies.

Their DNA is identical to that of the egg, and its analysis can identify an oocyte free of cancer-related mutations for transfer into the uterus. All this can be achieved without touching the embryo because the polar bodies are considered pre-embryonic.

Even this can, however, be criticized for medicalizing harmless genetic traits. Therefore, PGD should not used for creating genetic perfection but only to avoid severe disease. When done in the right setting, PGD can be a source of profound relief to concerned families since it can ensure that a dangerous genetic mutation will not be inherited by their progeny.

As reproductive technology evolves, clinicians must acquire up-to-speed knowledge of these new options to be able to select the right patient for the right procedure and for the right reason. Theologians, politicians and society at large will probably debate, discuss and decide upon standards for application.

V. Upender Rao, MD, FACP, practices at the Cancer and Blood Disease Center in Lecanto.

[Last modified December 18, 2006, 01:33:09]