TY - JOUR
T1 - Genetic variation in CYP17 and endometrial cancer risk
AU - Gaudet, Mia M.
AU - Lacey, James V.
AU - Lissowska, Jolanta
AU - Peplonska, Beata
AU - Brinton, Louise A.
AU - Chanock, Stephen
AU - Garcia-Closas, Montserrat
N1 - Funding Information:
Acknowledgments The authors would like to thank Neonila Szesze-nia-Dabrowska of the Nofer Institute of Occupational Medicine (Lodz, Poland) and Witold Zatonski of the M. Sklodowska-Curie Institute of Oncology and Cancer Center (Warsaw, Poland) for their contribution to the Polish Breast Cancer Study. Anita Soni (Westat, Rockville, MD, USA) and Pei Chao (IMS, Silver Spring, MD, USA) have been invaluable to the management of the study. This work would not be possible without the dedicated eVorts of the physicians, nurses, interviewers and study participants. This research was supported by funds from the intramural program of the National Cancer Institute, National Institutes of Health.
PY - 2008/3
Y1 - 2008/3
N2 - Genetic variation in CYP17 is suspected to be related to endometrial cancer risk based on its role in the regulation of steroid and non-steroid hormone biosynthesis. Reported associations between CYP17 and higher levels of estradiol in some studies suggest that the C allele of a T-to-C single nucleotide polymorphism (SNP) in the 5′UTR of CYP17 (rs743572) may be associated with an increased risk of hormone-related cancers. However, five relatively small epidemiologic studies of endometrial cancer have reported that women with the rs743572 C allele have a decreased risk of endometrial cancer. To examine this association, we genotyped rs743572 and eight other haplotype-tagging SNPs (htSNPs), which are estimated to capture >80% of the variation in CYP17 in a population-based study of 497 endometrial cancer cases and 1,024 controls in Poland. Significant associations were not found for rs743572 (per C allele: OR = 1.12, 95%CI 0.96-1.30; P-trend = 0.15), for individual htSNPs, or for extended haplotypes (global P-value = 0.60). When we pooled data from previously published studies with our own (a total of 1,004 endometrial cases and 1,907 controls), we observed significant study heterogeneity in summary estimates of the association between rs743572 and endometrial cancer, as well as evidence of publication bias. In conclusion, our data are not consistent with a decreased endometrial cancer risk associated with rs743572, as previously reported, or with other haplotype-tagging polymorphisms. Further evaluation in consortia is necessary to confirm potential weak associations between common variation in CYP17 and endometrial cancer risk and to address the concern of publication bias.
AB - Genetic variation in CYP17 is suspected to be related to endometrial cancer risk based on its role in the regulation of steroid and non-steroid hormone biosynthesis. Reported associations between CYP17 and higher levels of estradiol in some studies suggest that the C allele of a T-to-C single nucleotide polymorphism (SNP) in the 5′UTR of CYP17 (rs743572) may be associated with an increased risk of hormone-related cancers. However, five relatively small epidemiologic studies of endometrial cancer have reported that women with the rs743572 C allele have a decreased risk of endometrial cancer. To examine this association, we genotyped rs743572 and eight other haplotype-tagging SNPs (htSNPs), which are estimated to capture >80% of the variation in CYP17 in a population-based study of 497 endometrial cancer cases and 1,024 controls in Poland. Significant associations were not found for rs743572 (per C allele: OR = 1.12, 95%CI 0.96-1.30; P-trend = 0.15), for individual htSNPs, or for extended haplotypes (global P-value = 0.60). When we pooled data from previously published studies with our own (a total of 1,004 endometrial cases and 1,907 controls), we observed significant study heterogeneity in summary estimates of the association between rs743572 and endometrial cancer, as well as evidence of publication bias. In conclusion, our data are not consistent with a decreased endometrial cancer risk associated with rs743572, as previously reported, or with other haplotype-tagging polymorphisms. Further evaluation in consortia is necessary to confirm potential weak associations between common variation in CYP17 and endometrial cancer risk and to address the concern of publication bias.
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U2 - 10.1007/s00439-007-0454-8
DO - 10.1007/s00439-007-0454-8
M3 - Article
C2 - 18172694
AN - SCOPUS:39549120902
SN - 0340-6717
VL - 123
SP - 155
EP - 162
JO - Human genetics
JF - Human genetics
IS - 2
ER -