Polymorphic variation in CYP19 and the risk of breast cancer

• Published in: Carcinogenesis (New York) Vol. 22; no. 2; pp. 347 - 349
• Main Authors: Baxter, S.W., Choong, D.Y.H., Eccles, D.M., Campbell, I.G.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.02.2001; Oxford Publishing Limited (England)
• Subjects: Adult; Age of Onset; Aged; Aromatase - genetics; aromatase P450; Biological and medical sciences; Breast Neoplasms - etiology; Breast Neoplasms - genetics; CYP19 gene; DNA - analysis; Female; Gene Frequency; Genetic Variation; Genotype; Gynecology. Andrology. Obstetrics; Humans; Introns - genetics; Lymphocytes; Mammary gland diseases; Medical sciences; Middle Aged; Polymorphism, Genetic - genetics; Risk Factors; Tumors; England; United Kingdom; Great Britain; Europe; Human; Nucleotide sequence; Repeated sequence; Cytochrome P450; Genetic variant; Estrogen; Genotype; Biosynthesis; Malignant tumor; Carcinogenesis; Mammary gland diseases; Allele; Intron; Risk factor; Female; Genetics; Mammary gland; Polymorphism
• ISSN: 0143-3334; 1460-2180; 1460-2180
• DOI: 10.1093/carcin/22.2.347

The production of estrogen from androgen via the estrogen biosynthesis pathway is catalyzed by aromatase P450 (cyp19). We have assessed the frequency of allelic variants of the CYP19 intron 4 [TTTA]n repeat in 327 breast cancer cases and 253 controls from southern England. Previous studies have suggested that the [TTTA]10 repeat and [TTTA]12 repeat variants represent low penetrance breast cancer susceptibility alleles. Compared with controls our breast cancer cases had a statistically significant positive association with the [TTTA]10 allele (1.5 versus 0.2%, P = 0.028) and the [TTTA]8 allele (13.5 versus 8.7%, P = 0.012). The frequency of the [TTTA]12 allele was not significantly elevated in our study group compared with controls (2.3 versus 2.2%, P = 1.00). The CYP19 intron 4 [TTTA]n repeat is unlikely to have a functional effect on aromatase activity and it is more likely that the [TTTA]8 and [TTTA]10 variants are in linkage disequilibrium with other functional CYP19 variants.