TY - JOUR
T1 - A CYP19 (aromatase) polymorphism is associated with increased premenopausal breast cancer risk
AU - Talbott, Kathryn E.
AU - Gammon, Marilie D.
AU - Kibriya, Muhammad G.
AU - Chen, Yu
AU - Teitelbaum, Susan L.
AU - Long, Chang Min
AU - Gurvich, Irina
AU - Santella, Regina M.
AU - Ahsan, Habibul
N1 - Funding Information:
Acknowledgements Funded in part by grants U01 CA/ES66572, P30ES09089, and P30ES10126 from the National Cancer Institute and the National Institute of Environmental Health Sciences, a grant from the Cancer Research Foundation, and gifts from private citizens. We thank the following people for their valuable contributions to the Long Island Breast Cancer Study Project: members of the Long Island Breast Cancer Network; the thirty-one participating institutions on Long Island and in New York City, NY; our NIH collaborators, Gwen Colman, Ph.D., National Institutes of Environmental Health Sciences; G. Iris Obrams, M.D., Ph.D., formerly of the National Cancer Institute; members of the External Advisory Committee to the population based case-control study: Leslie Bernstein, Ph.D. (Committee Chair); Gerald Akland, M.S.; Barbara Balaban, M.S.W.; Blake Cady, M.D.; Dale Sandler, Ph.D.; Roy Shore, Ph.D.; and Gerald Wogan, Ph.D.; as well as other collaborators who assisted with various aspects of our data collection efforts including Gail Garbowski, M.P.H., Julie Brit-ton, Ph.D., Mary S. Wolff, Ph.D., Steve Stellman, Ph.D., Maureen Hatch, Ph.D., Geoff Kabat Ph.D., Bruce Levin, Ph.D. H. Leon Bradlow, Ph.D.; David Camann, B.S.; Martin Trent, B.S.; Ruby Se-nie, Ph.D.; Carla Maffeo, Ph.D.; Pat Montalvan; Gertrud Berkowitz, Ph.D.; Margaret Kemeny, M.D.; Mark Citron, M.D.; Freya Schnabel, M.D.; Allen Schuss, M.D.; Steven Hajdu, M.D.; and Vincent Vinceguerra, M.D.
PY - 2008/10
Y1 - 2008/10
N2 - Due to the established association between estrogen levels and breast cancer risk, polymorphic variation in genes regulating estrogen levels is thought to be related to breast cancer risk. Aromatase, the protein product of the CYP19 gene, is involved in the production of endogenous estrogens via androgen conversion. We examined whether polymorphic variation in CYP19 associated with increased breast cancer risk in a population based case-control study. We examined two single nucleotide polymorphisms (SNP), rs1008805 (A/G) and rs730154 (C/T), which have been shown to tag SNPs within two different haplotype blocks in CYP19. Among premenopausal women, the presence of at least one G allele at rs1008805 was significantly associated with an increase in the risk of breast cancer (OR = 1.72 [95% CI, 1.20-2.49]), especially with estrogen and progesterone receptor negative breast cancer (OR = 3.89 [1.74-8.70] and OR = 2.52 [1.26-5.05], respectively). No association was observed among postmenopausal women (OR = 1.06 [0.82-1.36]). There was no significant association between rs730154 and breast cancer, regardless of menopausal status. Our results suggest that premenopausal women carrying the G allele at CYP19 rs1008805 have increased risk of breast cancer. The finding supports the potential role of variation in estrogen biosynthesis genes in premenopausal breast cancer risk.
AB - Due to the established association between estrogen levels and breast cancer risk, polymorphic variation in genes regulating estrogen levels is thought to be related to breast cancer risk. Aromatase, the protein product of the CYP19 gene, is involved in the production of endogenous estrogens via androgen conversion. We examined whether polymorphic variation in CYP19 associated with increased breast cancer risk in a population based case-control study. We examined two single nucleotide polymorphisms (SNP), rs1008805 (A/G) and rs730154 (C/T), which have been shown to tag SNPs within two different haplotype blocks in CYP19. Among premenopausal women, the presence of at least one G allele at rs1008805 was significantly associated with an increase in the risk of breast cancer (OR = 1.72 [95% CI, 1.20-2.49]), especially with estrogen and progesterone receptor negative breast cancer (OR = 3.89 [1.74-8.70] and OR = 2.52 [1.26-5.05], respectively). No association was observed among postmenopausal women (OR = 1.06 [0.82-1.36]). There was no significant association between rs730154 and breast cancer, regardless of menopausal status. Our results suggest that premenopausal women carrying the G allele at CYP19 rs1008805 have increased risk of breast cancer. The finding supports the potential role of variation in estrogen biosynthesis genes in premenopausal breast cancer risk.
KW - Aromatase
KW - Breast cancer
KW - CYP19
KW - Haplotype
KW - Polymorphism
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U2 - 10.1007/s10549-007-9794-2
DO - 10.1007/s10549-007-9794-2
M3 - Article
C2 - 17975727
AN - SCOPUS:51649097937
SN - 0167-6806
VL - 111
SP - 481
EP - 487
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 3
ER -