Associations between aromatase CYP19 rs10046 polymorphism and breast cancer risk: from a case-control to a meta-analysis of 20,098 subjects.
Lifetime exposure to estrogen is a factor that plays an important role in the pathogenesis and progression of breast cancer. Genetic variants in genes of the biosynthesis and metabolism of estrogen have been associated with breast cancer risk. Among them, the CYP19 gene encodes for aromatase, the enzyme that catalyzes the conversion of androgens to estrogens. The rs10046 polymorphism on the CYP19 gene has been related to levels of circulating estradiol and to the estradiol/testosterone ratio. To date, epidemiological studies of rs10046 have been performed in different populations with contradictory results. In the present study, we have conducted a case-control analysis (522 cases and 1221 controls) in a Spanish population. Furthermore, we have performed a meta-analysis including 20,098 subjects (7,998 cases and 12,100 controls) to summarize the data available for rs10046 and breast cancer risk. An odds ratio (OR) with a 95% confidence interval (CI) was applied to assess the association. The results of our case-control study show an association between the carriers of at least one C allele (dominant model) and breast cancer risk (OR = 1.29, 95% CI 1.01-1.66, p-value = 0.038). The meta-analysis shows no significant association with breast cancer risk in any of the genetic models tested. The analysis by ethnic subgroups also failed to produce associations. The evaluation of heterogeneity, influence analysis, and publication bias confirms the reliability of the analysis. We can conclude that the rs10046 polymorphism on CYP19 by itself does not constitute breast cancer risk. We cannot, however, reject the possibility that it could contribute (interact), together with other genetic variants, to modify the circulating levels of estradiol.
Institute of Health Research INCLIVA, Valencia, Spain.
Begoña
B
Pineda
Miguel Ángel
MÁ
García-Pérez
Antonio
A
Cano
Ana
A
Lluch
Pilar
P
Eroles
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001141:Aromatase / Q000235:genetics*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results; D055815:Young Adult
D001141:Aromatase