Journal article
Alcohol-related breast cancer in postmenopausal women - effect of CYP19A1, PPARG and PPARGC1A polymorphisms on female sex-hormone levels and interaction with alcohol consumption and NSAID usage in a nested case-control study and a randomised controlled trial
Alcohol consumption is associated with increased risk of breast cancer (BC), and the underlying mechanism is thought to be sex-hormone driven. In vitro and observational studies suggest a mechanism involving peroxisome proliferator-activated receptor gamma (PPARγ) in a complex with peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and interaction with aromatase (encoded by CYP19A1).
Use of non-steroidal anti-inflammatory drugs (NSAID) may also affect circulating sex-hormone levels by modifying PPARγ activity. In the present study we assessed whether genetic variation in CYP19A1 is associated with risk of BC in a case-control study group nested within the Danish "Diet, Cancer and Health" cohort (ncases = 687 and ncontrols = 687) and searched for gene-gene interaction between CYP19A1 and PPARGC1A, and CYP19A1 and PPARG, and gene-alcohol and gene-NSAID interactions.
Association between the CYP19A1 polymorphisms and hormone levels was also examined among 339 non-HRT users. Incidence rate ratios were calculated based on Cox' proportional hazards model. Furthermore, we performed a pilot randomised controlled trial to determine the effect of the PPARG Pro(12)Ala polymorphism and the PPARγ stimulator Ibuprofen on sex-hormone levels following alcohol intake in postmenopausal women (n = 25) using linear regression.
Genetic variations in CYP19A1 were associated with hormone levels (estrone: P rs11070844 = 0.009, estrone sulphate: P rs11070844 = 0.01, P rs749292 = 0.004, P rs1062033 = 0.007 and P rs10519297 = 0.03, and sex hormone-binding globulin (SHBG): P rs3751591 = 0.03) and interacted with alcohol intake in relation to hormone levels (estrone sulphate: P interaction/rs2008691 = 0.02 and P interaction/rs1062033= 0.03, and SHBG: P interaction/rs11070844 = 0.03).
CYP19A1/rs3751591 was both associated with SHBG levels (P = 0.03) and with risk of BC (Incidence Rate Ratio = 2.12; 95 % Confidence Interval: 1.02-4.43) such that homozygous variant allele carriers had increased levels of serum SHBG and were at increased risk of BC. Acute intake of alcohol decreased blood estrone (P =
| Language: | English |
|---|---|
| Publisher: | BioMed Central |
| Year: | 2016 |
| Pages: | 283 |
| ISSN: | 14712407 |
| Types: | Journal article |
| DOI: | 10.1186/s12885-016-2317-y |
| ORCIDs: | 0000-0003-2623-6882 , 0000-0003-0609-6317 and Ravn-Haren, Gitte |
Alcohol consumption Breast cancer CYP19A1 Epidemiology Female sex-hormones NSAID PPARG Polymorphisms Prospective nested case-control study Randomised controlled trial SDG 3 - Good Health and Well-being
Adult Alcohol Drinking Alcohols Anti-Inflammatory Agents, Non-Steroidal Aromatase Breast Neoplasms CYP19A1 protein, human Female Genetic Association Studies Genotype Gonadal Steroid Hormones Humans Ibuprofen Middle Aged PPAR gamma Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Polymorphism, Single Nucleotide Postmenopause
