Markers Help Predict Breast Cancer Risk

Prediction model established to assess breast cancer risk in Asian women

July 9, 2010 | Dagny Stuart

The incidence of breast cancer among women in Asian countries is less than a third of the number diagnosed in most North American and European countries, but breast cancer cases are starting to spike in places like China, Japan, Korea and Singapore.

Currently, no risk prediction model is available to identify high-risk women in these countries for cost-efficient prevention of breast cancer.

Now, investigators with Vanderbilt-Ingram Cancer Center, the Shanghai Institute of Preventive Medicine and the Shanghai Cancer Institute have established a risk prediction model using both traditional clinical predictors and newly identified genetic markers.

Wei Zheng, M.D., Ph.D., M.P.H.

The study, led by VICC’s Wei Zheng, M.D., Ph.D., M.P.H., was published recently in the Journal of the National Cancer Institute.

“We wanted to know if newly identified genetic markers could improve risk prediction for breast cancer,” said Zheng, Ingram Professor of Cancer Research and director of the Vanderbilt Epidemiology Center.

“Establishing a breast cancer risk assessment model for women living in Asia could have substantial public health implications for breast cancer prevention because more than 60 percent of the world’s women live in Asia.”

The researchers studied 3,039 breast cancer patients and 3,082 control patients enrolled in the Shanghai Breast Cancer Study, a large, population-based study of female breast cancer survivors in China, which Vanderbilt University Medical Center, the Shanghai Cancer Institute and the Shanghai Institute of Preventive Medicine have carried out since 1996.

All of the women were interviewed regarding their clinical risk factors for breast cancer, including family history of breast cancer, age at first menstrual period, age at first live birth, waist-to-hip ratio and diagnosis of benign breast disease. The women also provided blood samples or other genetic material for investigation.

From those samples, researchers analyzed 12 single-nucleotide polymorphisms (SNPs) identified in recent genome-wide association studies as being linked to breast cancer risk. Eleven of those SNPs were identified in studies conducted among mostly women of European descent, and the 12th was identified by Zheng’s research team in a study conducted among Chinese women. The investigators discovered eight of those SNPs also were associated with breast cancer risk among Chinese women.

The researchers devised a genetic risk score based on the combined effects of these eight SNPs and confirmed that the score was one of the strongest predictors of breast cancer.

The investigators determined that the genetic risk score, along with a patient’s waist-to-hip ratio and a previous diagnosis of benign breast disease were the top three predictors of breast cancer risk.

“This is the first prediction model established to assess breast cancer risk in women living in Asian countries,” explained Zheng. “This study demonstrates the value of using both genetic and traditional predictors in classifying women into high- and low-risk groups for cost-efficient breast cancer prevention.”

Zheng said a screening program that targets women in the top 30 percent of risk as predicted by this model could identify approximately 47 percent of breast cancer cases in the general population and would thus increase the number detected by 56.7 percent compared with a program with no risk assessment.

“The relatively low incidence of breast cancer in Asian countries has made it difficult to justify the use of annual screening mammography for all women beginning at age 40. A viable alternative may be to use genetic and clinical predictors to identify high-risk women who should be targeted for screening,” said Zheng.

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