Mammographic density in breast cancer patients and polymorphisms in the estrogen pathway

Fragestellung: Breast density is an important parameter in relation to risk factors for breast cancer. It is not only associated with an increased risk of breast cancer, but also directly influences the selection of patient groups for scientific studies, as it influences the sensitivity and specificity of mammography. Hormone replacement therapy has also been reported to influence the risk of breast cancer and mammographic density. Furthermore mammographic density seems to be inheritable. Therefore we wanted to correlate genetic polymorphisms that influence the estrogen pathway with mammographic density in a cohort of breast cancer patients.

Methodik: A cohort of consecutive breast cancer cases from the University Breast Center Franken was taken for the study. Patients have been previously asked to take part in the Bavarian Breast Cancer and Control Trial (BBCC). Patients have been diagnosed with breast cancer between 2002 and 2005. A total of 490 patients out of 923 were assessable with both genotype information and mammographic density. Polymorphisms in the genes CYP19, ESR1, and PGR were analyzed with a TaqMan assay. Mammographic density was centrally reviewed according to the American College of Radiology BI-RADS™ atlas. Genotypes were correlated with phenotypes with chi-squared tests.

Ergebnisse: None of the examined polymorphisms showed a strong correlation with the mammographic density. Only polymorphism rs700519 in the aromatase gene CYP19 was associated with the mammographic density with a p-value of 0.046. Genotype frequencies for this polymorphism were for the homozygous wildtype, heterozygous and homozygous variant genotype 93,4%, 6.6% and 0% respectively. The wildtype genotype was more often correlated (54.6%) with a higher mammographic density of 3 or 4 and the heterozygous genotype only in 36.7% of the cases.

Schlussfolgerung: We have not been able to show strong associations between genotypes of the examined polymorphisms in the Genes CYP19, ESR1 and PGR and mammographic density. These findings are consistent with finding in another cohort, in which CYP19 was analyzed. Although some of the polymorphisms in CYP19 could be correlated with higher levels of circulating estrogen, there seems to be no effect on breast cancer risk or mammographic density.