Background: Telomeres are composed of tandem repeats of TTAGGG nucleotides located at chromosome ends. Telomere length is inversely correlated with age, smoking, and body mass index, and shortens following significant chemotherapy exposure. Telomere shortening in peripheral blood leukocytes has been associated with various cancers, including bladder, small cell lung, renal cell, basal cell, and head and neck cancers. A non-significant trend for shorter telomeres has also been observed in pre-menopausal women with breast cancer. Based on findings in Li-Fraumeni syndrome families showing a significant association between shortened telomeres and familial cancer risk in individuals with a germline p53 mutation, we sought to compare blood telomere length from individuals with familial breast cancer vs non-familial sporadic breast cancer patients. We hypothesized that shortened telomeres would be a marker for familial breast cancer in the absence of a BRCA mutation. Methods: Non-smoking women treated at the Stanford Breast Cancer Oncology Clinic or Cancer Genetics Clinic between 2003 and 2008 were eligible. Samples consisted of DNA extracted from whole blood from 21 women with sporadic breast cancer, defined as no familial or previous personal history of cancer, compared with 92 women with breast cancer and one or more first degree relatives with breast cancer. The familial breast cancer group consisted of 26 women testing positive for a BRCA1/2 mutation and 66 women wild-type for BRCA1/2. Women in the sporadic group were aged 40-57 and in the familial group were aged 35-65. Using quantitative real-time PCR run in triplicate, we measured relative telomere length by calculating the telomere repeat to single copy gene ratio (T/S). Results were compared using an unpaired t test. Results: Median age was 50 in the sporadic group and 49 in the familial group. Each group had similar variability in the amount of chemotherapy received, and all had received four or less cycles at the time of specimen collection. No statistically significant difference was observed in telomere length between the BRCA-positive (mean T/S = 1.38) and BRCA-negative (mean T/S = 1.28) familial breast cancer groups. Additionally, among the 67 BRCA-negative women, no statistically significant difference was noted between women who had a single first-degree family member affected with breast cancer (mean T/S = 1.29) and those who had two, three, or four first-degree family members affected (mean T/S = 1.27). Blood relative telomere length in the sporadic breast cancer group was shorter than in the familial group (mean T/S = 1.15 vs mean T/S = 1.31, p < 0.07). Summary and Significance: This ongoing study is the first to compare blood telomere length in familial and sporadic breast cancer, and our preliminary results suggest a possible unique association of shortened telomeres with sporadic breast cancer incidence not evident in cases of familial breast cancer.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3036.

100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

American Association for Cancer Research
2009