Exposures in early life: associations with DNA promoter methylation in breast tumors
There is evidence that epigenetic changes occur early in breast carcinogenesis. We hypothesized that early-life exposures associated with breast cancer would be associated with epigenetic alterations in breast tumors. In particular, we examined DNA methylation patterns in breast tumors in associatio...
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| Veröffentlicht in: | Journal of developmental origins of health and disease 2013-04, Vol.4 (2), p.182-190 |
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| creator | Tao, M.-H. Marian, C. Shields, P. G. Potischman, N. Nie, J. Krishnan, S. S. Berry, D. L. Kallakury, B. V. Ambrosone, C. Edge, S. B. Trevisan, M. Winston, J. Freudenheim, J. L. |
| description | There is evidence that epigenetic changes occur early in breast carcinogenesis. We hypothesized that early-life exposures associated with breast cancer would be associated with epigenetic alterations in breast tumors. In particular, we examined DNA methylation patterns in breast tumors in association with several early-life exposures in a population-based case–control study. Promoter methylation of E-cadherin, p16 and RAR-β2 genes was assessed in archived tumor blocks from 803 cases with real-time methylation-specific PCR. Unconditional logistic regression was used for case–case comparisons of those with and without promoter methylation. We found no differences in the prevalence of DNA methylation of the individual genes by age at menarche, age at first live birth and weight at age 20. In case–case comparisons of premenopausal breast cancer, lower birth weight was associated with increased likelihood of E-cadherin promoter methylation (OR = 2.79, 95% CI, 1.15–6.82, for ⩽2.5 v. 2.6–2.9 kg); higher adult height with RAR-β2 methylation (OR = 3.34, 95% CI, 1.19–9.39, for ⩾1.65 v. |
| doi_str_mv | 10.1017/S2040174412000694 |
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G. ; Potischman, N. ; Nie, J. ; Krishnan, S. S. ; Berry, D. L. ; Kallakury, B. V. ; Ambrosone, C. ; Edge, S. B. ; Trevisan, M. ; Winston, J. ; Freudenheim, J. L.</creator><creatorcontrib>Tao, M.-H. ; Marian, C. ; Shields, P. G. ; Potischman, N. ; Nie, J. ; Krishnan, S. S. ; Berry, D. L. ; Kallakury, B. V. ; Ambrosone, C. ; Edge, S. B. ; Trevisan, M. ; Winston, J. ; Freudenheim, J. L.</creatorcontrib><description>There is evidence that epigenetic changes occur early in breast carcinogenesis. We hypothesized that early-life exposures associated with breast cancer would be associated with epigenetic alterations in breast tumors. In particular, we examined DNA methylation patterns in breast tumors in association with several early-life exposures in a population-based case–control study. Promoter methylation of E-cadherin, p16 and RAR-β2 genes was assessed in archived tumor blocks from 803 cases with real-time methylation-specific PCR. Unconditional logistic regression was used for case–case comparisons of those with and without promoter methylation. We found no differences in the prevalence of DNA methylation of the individual genes by age at menarche, age at first live birth and weight at age 20. In case–case comparisons of premenopausal breast cancer, lower birth weight was associated with increased likelihood of E-cadherin promoter methylation (OR = 2.79, 95% CI, 1.15–6.82, for ⩽2.5 v. 2.6–2.9 kg); higher adult height with RAR-β2 methylation (OR = 3.34, 95% CI, 1.19–9.39, for ⩾1.65 v. <1.60 m); and not having been breastfed with p16 methylation (OR = 2.75, 95% CI, 1.14–6.62). Among postmenopausal breast cancers, birth order was associated with increased likelihood of p16 promoter methylation. Being other than first in the birth order was inversely associated with likelihood of ⩾1 of the three genes being methylated for premenopausal breast cancers, but positively associated with methylation in postmenopausal women. These results suggest that there may be alterations in methylation associated with early-life exposures that persist into adulthood and affect breast cancer risk.</description><identifier>ISSN: 2040-1744</identifier><identifier>EISSN: 2040-1752</identifier><identifier>DOI: 10.1017/S2040174412000694</identifier><identifier>PMID: 25054684</identifier><language>eng</language><publisher>Cambridge, UK: Cambridge University Press</publisher><subject>Age ; Birth order ; Birth weight ; Breast cancer ; Breastfeeding & lactation ; Cancer therapies ; Cell cycle ; Deoxyribonucleic acid ; DNA ; DNA methylation ; Epidemiology ; Epigenetics ; Family medical history ; Famine ; Gene expression ; Health risk assessment ; Menarche ; Nutrition ; Original Article ; Pregnancy ; Studies ; Tumors</subject><ispartof>Journal of developmental origins of health and disease, 2013-04, Vol.4 (2), p.182-190</ispartof><rights>Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c471t-b9055a5815fb7647b359235270146d356333ac595459fed1c8af7590abf4e4b43</citedby><cites>FETCH-LOGICAL-c471t-b9055a5815fb7647b359235270146d356333ac595459fed1c8af7590abf4e4b43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.cambridge.org/core/product/identifier/S2040174412000694/type/journal_article$$EHTML$$P50$$Gcambridge$$H</linktohtml><link.rule.ids>164,230,314,776,780,881,27901,27902,55603</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25054684$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tao, M.-H.</creatorcontrib><creatorcontrib>Marian, C.</creatorcontrib><creatorcontrib>Shields, P. G.</creatorcontrib><creatorcontrib>Potischman, N.</creatorcontrib><creatorcontrib>Nie, J.</creatorcontrib><creatorcontrib>Krishnan, S. S.</creatorcontrib><creatorcontrib>Berry, D. L.</creatorcontrib><creatorcontrib>Kallakury, B. V.</creatorcontrib><creatorcontrib>Ambrosone, C.</creatorcontrib><creatorcontrib>Edge, S. B.</creatorcontrib><creatorcontrib>Trevisan, M.</creatorcontrib><creatorcontrib>Winston, J.</creatorcontrib><creatorcontrib>Freudenheim, J. L.</creatorcontrib><title>Exposures in early life: associations with DNA promoter methylation in breast tumors</title><title>Journal of developmental origins of health and disease</title><addtitle>J Dev Orig Health Dis</addtitle><description>There is evidence that epigenetic changes occur early in breast carcinogenesis. We hypothesized that early-life exposures associated with breast cancer would be associated with epigenetic alterations in breast tumors. In particular, we examined DNA methylation patterns in breast tumors in association with several early-life exposures in a population-based case–control study. Promoter methylation of E-cadherin, p16 and RAR-β2 genes was assessed in archived tumor blocks from 803 cases with real-time methylation-specific PCR. Unconditional logistic regression was used for case–case comparisons of those with and without promoter methylation. We found no differences in the prevalence of DNA methylation of the individual genes by age at menarche, age at first live birth and weight at age 20. In case–case comparisons of premenopausal breast cancer, lower birth weight was associated with increased likelihood of E-cadherin promoter methylation (OR = 2.79, 95% CI, 1.15–6.82, for ⩽2.5 v. 2.6–2.9 kg); higher adult height with RAR-β2 methylation (OR = 3.34, 95% CI, 1.19–9.39, for ⩾1.65 v. <1.60 m); and not having been breastfed with p16 methylation (OR = 2.75, 95% CI, 1.14–6.62). Among postmenopausal breast cancers, birth order was associated with increased likelihood of p16 promoter methylation. Being other than first in the birth order was inversely associated with likelihood of ⩾1 of the three genes being methylated for premenopausal breast cancers, but positively associated with methylation in postmenopausal women. These results suggest that there may be alterations in methylation associated with early-life exposures that persist into adulthood and affect breast cancer risk.</description><subject>Age</subject><subject>Birth order</subject><subject>Birth weight</subject><subject>Breast cancer</subject><subject>Breastfeeding & lactation</subject><subject>Cancer therapies</subject><subject>Cell cycle</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA methylation</subject><subject>Epidemiology</subject><subject>Epigenetics</subject><subject>Family medical history</subject><subject>Famine</subject><subject>Gene expression</subject><subject>Health risk assessment</subject><subject>Menarche</subject><subject>Nutrition</subject><subject>Original Article</subject><subject>Pregnancy</subject><subject>Studies</subject><subject>Tumors</subject><issn>2040-1744</issn><issn>2040-1752</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>BENPR</sourceid><recordid>eNp1kU1LxDAQhoMorqg_wIsEPFfzMWlaD4Lo-gGiB_Uc0jZ1s7TNmqTq_nu7uq6KeJph5n2fGWYQ2qPkkBIqj-4ZgSECUEYISXNYQ1uLUkKlYOurHGCEdkOYDhrCKQyWTTRigghIM9hCD-O3mQu9NwHbDhvtmzlubG2OsQ7BlVZH67qAX22c4PPbUzzzrnXReNyaOJk3H-2Fs_BGh4hj3zofdtBGrZtgdpdxGz1ejB_OrpKbu8vrs9ObpARJY1LkRAgtMirqQqYgCy5yxgWThEJacZFyznUpcgEir01Fy0zXUuREFzUYKIBvo5NP7qwvWlOVpoteN2rmbav9XDlt1e9OZyfqyb0oEDxngg6AgyXAu-fehKimrvfdsLNijEguIZN8UNFPVeldCN7UqwmUqMUv1J9fDJ79n6utHF-XHwR8CdVt4W31ZL5n_499B0PHk08</recordid><startdate>201304</startdate><enddate>201304</enddate><creator>Tao, M.-H.</creator><creator>Marian, C.</creator><creator>Shields, P. 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G.</au><au>Potischman, N.</au><au>Nie, J.</au><au>Krishnan, S. S.</au><au>Berry, D. L.</au><au>Kallakury, B. V.</au><au>Ambrosone, C.</au><au>Edge, S. B.</au><au>Trevisan, M.</au><au>Winston, J.</au><au>Freudenheim, J. L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Exposures in early life: associations with DNA promoter methylation in breast tumors</atitle><jtitle>Journal of developmental origins of health and disease</jtitle><addtitle>J Dev Orig Health Dis</addtitle><date>2013-04</date><risdate>2013</risdate><volume>4</volume><issue>2</issue><spage>182</spage><epage>190</epage><pages>182-190</pages><issn>2040-1744</issn><eissn>2040-1752</eissn><abstract>There is evidence that epigenetic changes occur early in breast carcinogenesis. We hypothesized that early-life exposures associated with breast cancer would be associated with epigenetic alterations in breast tumors. In particular, we examined DNA methylation patterns in breast tumors in association with several early-life exposures in a population-based case–control study. Promoter methylation of E-cadherin, p16 and RAR-β2 genes was assessed in archived tumor blocks from 803 cases with real-time methylation-specific PCR. Unconditional logistic regression was used for case–case comparisons of those with and without promoter methylation. We found no differences in the prevalence of DNA methylation of the individual genes by age at menarche, age at first live birth and weight at age 20. In case–case comparisons of premenopausal breast cancer, lower birth weight was associated with increased likelihood of E-cadherin promoter methylation (OR = 2.79, 95% CI, 1.15–6.82, for ⩽2.5 v. 2.6–2.9 kg); higher adult height with RAR-β2 methylation (OR = 3.34, 95% CI, 1.19–9.39, for ⩾1.65 v. <1.60 m); and not having been breastfed with p16 methylation (OR = 2.75, 95% CI, 1.14–6.62). Among postmenopausal breast cancers, birth order was associated with increased likelihood of p16 promoter methylation. Being other than first in the birth order was inversely associated with likelihood of ⩾1 of the three genes being methylated for premenopausal breast cancers, but positively associated with methylation in postmenopausal women. These results suggest that there may be alterations in methylation associated with early-life exposures that persist into adulthood and affect breast cancer risk.</abstract><cop>Cambridge, UK</cop><pub>Cambridge University Press</pub><pmid>25054684</pmid><doi>10.1017/S2040174412000694</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Age Birth order Birth weight Breast cancer Breastfeeding & lactation Cancer therapies Cell cycle Deoxyribonucleic acid DNA DNA methylation Epidemiology Epigenetics Family medical history Famine Gene expression Health risk assessment Menarche Nutrition Original Article Pregnancy Studies Tumors |
| title | Exposures in early life: associations with DNA promoter methylation in breast tumors |
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