New Approach To Detect Rare Genetic Variants Aims To Help Women Evaluate Hormone Replacement Therapy And Breast Cancer Risk

Main Category: Menopause
Also Included In: Breast Cancer;  Genetics;  Cancer / Oncology
Article Date: 18 Sep 2008 - 4:00 PDT

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Perlegen, a leader in discovering clinically important genetic variations that affect patients' drug response and predisposition to disease, announced today that it has launched a new, proprietary approach to discovering rare genetic variations. The company is now employing this approach in a study of women who have received hormone replacement therapy, to survey a large proportion of the expressed genome for the presence of rare genetic variants that alter women's risk of developing breast cancer.

Perlegen has already identified common genetic variants with proven, quantifiable associations to disease risk and drug response profiles, including common variants related to the risk of developing breast cancer. But while common variants can provide valuable information, they do not explain all of the genetic factors associated with a particular clinical outcome. This new approach will enable Perlegen to efficiently identify more of the genetic basis behind the differences in patients' disease risks and response to drugs.

Common variants can be found by "genotyping," or studying the most prevalent genetic variants, called single nucleotide polymorphisms (or "SNPs"). Rarer variants, however, must be found through "sequencing," a more involved process that looks at the entire genetic code in a region of interest to discover not only any single-base changes from its known sequence, but also any insertions or deletions of code. Perlegen's sequencing approach targets the sections of the genome that are expressed as proteins, since even with fast, second-generation sequencing, addressing the entire genome in hundreds of cases and controls remains prohibitively expensive. Perlegen's new approach uses an innovative sample preparation method, automated processing on a next-generation sequencing discovery platform and advanced data analysis methods.

"Perlegen's pioneering use of sequencing to discover rarer genetic variants associated with increased risk of disease or drug side effects will make clinical testing an even more powerful tool," said Bryan Walser, M.D., CEO of Perlegen. "This new information will build upon our earlier work in common variants for breast cancer to allow physicians and patients to make better-informed choices about treatment options based on information associated with the individual's particular genetics, enabling medicine that's truly tailored to each individual. For a woman who has some identified risk factors for breast cancer, such as immediate family history, and is considering hormone replacement therapy to ameliorate the symptoms of menopause, this additional information could be extremely valuable."

The data for the Perlegen study of hormone replacement therapy and breast cancer risk comes from the Women's Health Initiative (WHI), a long-term national health study that focuses on strategies for preventing heart disease, breast and colorectal cancer and fracture in postmenopausal women. Since 1993, the WHI study has involved more than 161,000 women ages 50-79 in one of the most definitive, far-reaching programs of research on women's health ever undertaken in the United States.

Perlegen expects to complete its breast cancer study in early 2009. The company will continue to apply this sequencing technology to identify markers that help to guide other key healthcare decisions.

About Perlegen

Perlegen's mission is to discover and commercialize genetic variations that can make a difference to patients and physicians. The company's expertise is in understanding human genetic variation within and across diverse patient populations and in conducting studies aimed at identifying those variations that are predictive of drug response, including both toxicity and efficacy.

Perlegen