Abstract 4483: Early life exposures and promoter methylation in breast cancer: the Western New York Exposures and Breast Cancer (WEB) Study

Abstract Background: Exposures in the peri- and post-natal period (in utero, infancy, childhood, and adolescence) are associated with breast cancer risk, particularly premenopausal breast cancer. Epigenetic alterations in response to these exposures may play a critical role in early life, and then influence breast cancer risk in adult life. Using archived tumor blocks from incident breast cancer cases in a population-based the Western New York Exposures and Breast Cancer Study (WEB Study), we examined the association between early life exposures and promoter methylation of three tumor suppressor genes (p16, E-cadherin, and RARα 2 ). Method: DNA samples isolated from 803 paraffin embedded tumor tissue were analyzed for hypermethylation status using real time methylation-specific polymerase chain reaction (MSP). Unconditional logistic regression was used for case-case comparisons of those with and without promoter methylation to estimate odds ratios (ORs) and 95% confidence intervals (95% CI) for associations of early life exposure with the likelihood of promoter methylation. Results: Among premenopausal breast tumors, compared to those with normal birth weight (2.6-3.9 kg), there was increased likelihood of E - cadherin gene hypermethylation in tumors from lower birth weight (≥ 2.5 kg) (OR = 2.79, 95% CI, 1.15-6.82). Height was positively associated with the likelihood of hypermethylation of RAR-α 2 gene in premenopausal tumors (OR =3.34, 95% CI, 1.19-9.39). For p16, there was significant differences in the likelihood of promoter methylation of p16 in relation to not having been breast fed in premenopausal tumors (OR = 2.75, 95% CI, 1.14-6.62). Among postmenopausal breast cancers, birth order was associated with increased likelihood of p16 promoter methylation. The likelihood of promoter methylation of the individual genes did not differ by maternal age at delivery, maternal height, age at menarche, age of first live birth, and weight at age 20 in either strata of menopause Conclusion: We found lower birth weight, not having been breast fed, and higher height were associated with promoter methylation of E - cadherin, p16 and RAR-α 2 premenopausal breast tumors, respectively, suggesting that early life exposures may affect breast carcinogenesis among younger women through aberrant DNA methylation. Further studies of more genes and larger sample size may provide additional insight. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4483. doi:1538-7445.AM2012-4483