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Medientyp: E-Artikel Titel: Estrogen‐metabolizing gene polymorphisms in the assessment of breast carcinoma risk and fibroadenoma risk in Caucasian women Beteiligte: Hefler, Lukas A.; Tempfer, Clemens B.; Grimm, Christoph; Lebrecht, Antje; Ulbrich, Eva; Heinze, Georg; Leodolter, Sepp; Schneeberger, Christian; Mueller, Manfred W.; Muendlein, Axel; Koelbl, Heinz Erschienen: Wiley, 2004 Erschienen in: Cancer Sprache: Englisch DOI: 10.1002/cncr.20361 ISSN: 0008-543X; 1097-0142 Schlagwörter: Cancer Research ; Oncology Entstehung: Anmerkungen: Beschreibung: <jats:title>Abstract</jats:title><jats:sec><jats:title>BACKGROUND</jats:title><jats:p>Genes encoding enzymes involved in estrogen metabolism are held to be candidate genes for associations with breast disease. In these candidate genes, no critical combination of single‐nucleotide polymorphisms (SNPs) for assessing breast carcinoma risk has been reported to date.</jats:p></jats:sec><jats:sec><jats:title>METHODS</jats:title><jats:p>In a large case–control study, the authors investigated 10 estrogen‐metabolizing SNPs in 396 patients with breast carcinoma, 154 patients with fibroadenoma, and 1936 healthy control patients without breast carcinoma in their personal history. The following 10 SNPs were analyzed using sequencing‐on‐chip technology via a solid‐phase polymerase chain reaction assay performed on oligonucleotide microarrays: catechol‐O‐methyltransferase Val158Met G→A, 17‐beta‐hydroxysteroid dehydrogenase type 1 vIV A→C, cytochrome P‐450 (CYP) family 17 A2 allele T→C, <jats:italic>CYP1A1</jats:italic>‐1 <jats:italic>Msp</jats:italic>I restriction fragment length polymorphism (RFLP) T→C, <jats:italic>CYP1A1‐2</jats:italic> Ile462Val A→G, <jats:italic>CYP19‐1</jats:italic> Trp39Arg T→C, <jats:italic>CYP19‐2</jats:italic> Arg264Cys C→T, <jats:italic>CYP19‐3 Cys1558</jats:italic>Thr C→T, steroid‐5‐alpha reductase type 2 Val89Leu G→C, and vitamin D receptor <jats:italic>Bsm</jats:italic>I RFLP. A total of 21,350 genotypes were evaluated. Associations and two‐way interaction models were calculated using stepwise logistic regression.</jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p>In a multiple model, <jats:italic>CYP1A1‐1</jats:italic> (<jats:italic>P</jats:italic> = 0.004) and <jats:italic>CYP1A1‐2</jats:italic> (<jats:italic>P</jats:italic> = 0.03) were found to be associated with significantly decreased and increased risks of breast carcinoma, respectively. When two‐way interactions involving investigated SNPs were ascertained, no significant interactions among polymorphisms were noted. Comparison of patients with fibroadenoma with control patients revealed significantly increased and decreased risks of fibroadenoma when the mutant alleles of <jats:italic>CYP17</jats:italic> (<jats:italic>P</jats:italic> = 0.02) and <jats:italic>CYP1A1‐1</jats:italic> (<jats:italic>P</jats:italic> = 0.04), respectively, were present.</jats:p></jats:sec><jats:sec><jats:title>CONCLUSIONS</jats:title><jats:p>The authors obtained the first SNP data indicating that <jats:italic>CYP17</jats:italic> and <jats:italic>CYP1A1‐1</jats:italic> play a role in the pathogenesis of fibroadenoma. Although the authors were not able to develop interaction models involving SNPs, they did provide evidence that <jats:italic>CYP1A1</jats:italic> is a low‐penetrance susceptibility gene with respect to breast carcinoma in a large series of Caucasian women. Cancer 2004. © 2004 American Cancer Society.</jats:p></jats:sec> Zugangsstatus: Freier Zugang