TY - JOUR
T1 - Genetic variation in five genes important in telomere biology and risk for breast cancer
AU - Savage, S. A.
AU - Chanock, S. J.
AU - Lissowska, J.
AU - Brinton, L. A.
AU - Richesson, D.
AU - Peplonska, B.
AU - Bardin-Mikolajczak, A.
AU - Zatonski, W.
AU - Szeszenia-Da̧browska, N.
AU - Garcia-Closas, M.
N1 - Funding Information:
This work would not be possible without the dedicated efforts of the physicians, nurses, interviewers and study participants. Anita Soni (Westat, Rockville, MD, USA) and Pei Chao (IMS, Silver Spring, MD, USA) have been invaluable to the management of the study. We thank Dr Meredith Yeager for valuable technical assistance. This research was supported (in part) by the Intramural Research Program of the National Cancer Institute of the National Institutes of Health.
PY - 2007/9/11
Y1 - 2007/9/11
N2 - Telomeres, consisting of TTAGGG nucleotide repeats and a protein complex at chromosome ends, are critical for maintaining chromosomal stability. Genomic instability, following telomere crisis, may contribute to breast cancer pathogenesis. Many genes critical in telomere biology have limited nucleotide diversity, thus, single nucleotide polymorphisms (SNPs) in this pathway could contribute to breast cancer risk. In a population-based study of 1995 breast cancer cases and 2296 controls from Poland, 24 SNPs representing common variation in POT1, TEP1, TERF1, TERF2 and TERT were genotyped. We did not identify any significant associations between individual SNPs or haplotypes and breast cancer risk; however, data suggested that three correlated SNPs in TERT (-1381C>T, -244C>T, and Ex2-659G>A) may be associated with reduced risk of breast cancer among individuals with a family history of breast cancer (odds ratios 0.73, 0.66, and 0.57, 95% confidence intervals 0.53-1.00, 0.46-0.95 and 0.39-0.84, respectively). In conclusion, our data do not support substantial overall associations between SNPs in telomere pathway genes and breast cancer risk. Intriguing associations with variants in TERT among women with a family history of breast cancer warrant follow-up in independent studies.
AB - Telomeres, consisting of TTAGGG nucleotide repeats and a protein complex at chromosome ends, are critical for maintaining chromosomal stability. Genomic instability, following telomere crisis, may contribute to breast cancer pathogenesis. Many genes critical in telomere biology have limited nucleotide diversity, thus, single nucleotide polymorphisms (SNPs) in this pathway could contribute to breast cancer risk. In a population-based study of 1995 breast cancer cases and 2296 controls from Poland, 24 SNPs representing common variation in POT1, TEP1, TERF1, TERF2 and TERT were genotyped. We did not identify any significant associations between individual SNPs or haplotypes and breast cancer risk; however, data suggested that three correlated SNPs in TERT (-1381C>T, -244C>T, and Ex2-659G>A) may be associated with reduced risk of breast cancer among individuals with a family history of breast cancer (odds ratios 0.73, 0.66, and 0.57, 95% confidence intervals 0.53-1.00, 0.46-0.95 and 0.39-0.84, respectively). In conclusion, our data do not support substantial overall associations between SNPs in telomere pathway genes and breast cancer risk. Intriguing associations with variants in TERT among women with a family history of breast cancer warrant follow-up in independent studies.
KW - Breast cancer
KW - Haplotype
KW - Single nucleotide polymorphism
KW - TERF2
KW - TERT
KW - Telomere
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U2 - 10.1038/sj.bjc.6603934
DO - 10.1038/sj.bjc.6603934
M3 - Article
C2 - 17848914
AN - SCOPUS:34548588392
SN - 0007-0920
VL - 97
SP - 832
EP - 836
JO - British journal of cancer
JF - British journal of cancer
IS - 6
ER -