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    Research Grants Awarded

    Telomere Dysfunction and Breast Cancer Risk

    Study Section:
    RISK and Prevention, Epidemiology

    Scientific Abstract:
    Emerging evidence indicate that telomere dysfunction is associated with the initiation and development of malignant tumors. Individuals with clinical conditions related to deficiencies in telomere maintenance are prone to cancers. Recent data also indicate that short telomeres in blood mononuclear cells are associated with increased risk of lung, head and neck, renal cell, and bladder cancers. The role of telomere length maintenance and breast cancer risk, however, remains to be determined. Hypothesis/objective: We hypothesize that women with deficiencies in telomere length maintenance, as defined by short telomeres in blood lymphocytes, will have an increased risk of breast cancer. Specific aims: 1) to determine the association of telomere length in blood lymphocytes and the risk of breast cancer, and 2) to determine the association of polymorphisms in telomere maintenance genes and the risk of breast cancer. Study design: We will compare the telomere length in blood lymphocytes of 300 women newly diagnosed with invasive breast cancer to 300 cancer-free women controls. Controls will be frequency matched to cases on age, race and area of residence. Telomere length in blood lymphocytes will be determined using real-time quantitative PCR. In addition, eight polymorphisms in genes involved in telomere length maintenance will also be determined and compared between cases and controls. Potential outcomes and benefits of the research: The proposed study will determine whether short telomeres in blood lymphocytes, which reflects a deficiency in telomere length maintenance, will be associated with an increased risk of breast cancer. We expect that women with short telomeres in their blood lymphocytes will have an increased risk of breast cancer. We also expect that the women with “higher-risk” genotypes in telomere maintenance genes will have an increased risk of breast cancer. This study will have the potential to identify new genetic risk factors for breast cancer. By providing critical new information about the role of telomere length maintenance in breast cancer susceptibility, our study will provide new insight for understanding the biologic process that is involved in the development of breast cancer.

    Lay Abstract:
    Telomeres are structures that cap the ends of chromosomes. They serve as the biologic clock that controls cell division. Functional telomeres are essential for maintaining the stability of the chromosome structure. Normal human cells are not able to replicate the extreme ends of their chromosomes and the telomeres shorten with each cell division. When a cell’s telomeres shorten to a critical point, the telomeres will lose their normal protective function (this is called telomere dysfunction). Telomere dysfunction is linked to the development of many types of cancer, including breast cancer, in genetically engineered mice with short and dysfunctional telomeres. Individuals with diseases related to deficiency in telomere maintenance have an increased risk to develop cancer. Short telomeres are frequently seen in breast tissue of pre-cancer lesions and cancer cells. Recent data also indicate that short telomeres in blood white cells are associated with increased risk of lung, head and neck, kidney, and bladder cancers. The role of telomere length maintenance and the risk of breast cancer, however, remain to be determined. We propose to conduct a case-control study to examine the relationship of telomere length in blood lymphocytes and the risk of breast cancer. Cases will be women newly diagnosed with invasive breast cancer recruited at Lombardi Comprehensive Cancer Center and controls will be cancer-free women with similar age and race distribution as cases. Telomere length in blood lymphocytes will be determined and compared between breast cancer patients and the cancer-free women controls. In addition, genetic variations in genes that control telomere length will also be examined and compared between cases and controls. We expect that women with short telomeres will have an increased risk of breast cancer. We also expect that the women with “higher-risk” genotypes in telomere maintenance genes will have an increased risk of breast cancer. This study will have the potential to identify new genetic risk factors for breast cancer and provide new insight for understanding breast cancer etiology.