Reproductive characteristics are associated with gene-specific promoter methylation status in breast cancern

被引:6
|
作者
McCullough, Lauren E. [1 ]
Collin, Lindsay J. [1 ]
Conway, Kathleen [2 ]
White, Alexandra J. [3 ]
Cho, Yoon Hee [4 ]
Shantakumar, Sumitra [5 ]
Terry, Mary Beth [6 ]
Teitelbaum, Susan L. [9 ]
Neugut, Alfred, I [6 ,7 ]
Santella, Regina M. [8 ]
Chen, Jia [6 ,10 ,11 ]
Gammon, Marilie D. [2 ]
机构
[1] Emory Univ, Dept Epidemiol, Atlanta, GA 30322 USA
[2] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA
[3] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA
[4] Univ Montana, Dept Biomed & Pharmaceut Sci, Missoula, MT 59812 USA
[5] GlaxoSmithKline, Epidemiol Real World Evidence & Digital Platforms, Singapore, Singapore
[6] Columbia Univ, Dept Epidemiol, New York, NY 10032 USA
[7] Columbia Univ, Dept Med, New York, NY 10032 USA
[8] Columbia Univ, Dept Environm Hlth Sci, New York, NY 10032 USA
[9] Icahn Sch Med Mt Sinai, Dept Environm Med & Publ Hlth, New York, NY 10029 USA
[10] Icahn Sch Med Mt Sinai, Dept Pediat, New York, NY 10029 USA
[11] Icahn Sch Med Mt Sinai, Dept Oncol Sci, New York, NY 10029 USA
基金
美国国家卫生研究院;
关键词
Breast Cancer; Epidemiology; Epigenetics; Reproductive characteristics; DNA methylation; DNA METHYLATION; RISK-FACTORS; LIFE-STYLE; EXPRESSION; HYPERMETHYLATION; CADHERIN; WOMEN; PCR;
D O I
10.1186/s12885-019-6120-4
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Reproductive characteristics are well-established risk factors for breast cancer, but the underlying mechanisms are not fully resolved. We hypothesized that altered DNA methylation, measured in tumor tissue, could act in concert with reproductive factors to impact breast carcinogenesis. Methods: Among a population-based sample of women newly diagnosed with first primary breast cancer, reproductive history was assessed using a life-course calendar approach in an interviewer-administered questionnaire. Methylation-specific polymerase chain reaction and Methyl Light assays were used to assess gene promotor methylation status (methylated vs. unmethylated) for 13 breast cancer-related genes in archived breast tumor tissue. We used case-case unconditional logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for associations with age at menarche and parity (among 855 women), and age at first birth and lactation (among a subset of 736 parous women) in association with methylation status. Results: Age at first birth > 27 years, compared with < 23 years, was associated with lower odds of methylation of CDH1 (OR = 0.44, 95% CI = 0.20-0.99) and TWIST1 (OR = 0.48, 95% CI = 0.28-0.82), and higher odds of methylation of BRCA1 (OR = 1.63, 95% CI = 1.14- 2.35). Any vs. no lactation was associated with higher odds of methylation of the PGR gene promoter (OR = 1.59, 95% CI = 1.01-2.49). No associations were noted for parity and methylation in any of the genes assayed. Conclusions: Our findings indicate that age at first birth, lactation and, perhaps age at menarche, are associated with gene promoter methylation in breast cancer, and should be confirmed in larger studies with robust gene coverage.
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页数:9
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