Plasma B-vitamins and one-carbon metabolites and the risk of breast cancer in younger women
Purpose We examined the association of plasma B-vitamins and metabolites, and related genetic variants, with risk of breast cancer among predominantly premenopausal women. Methods We conducted a nested case–control study within the Nurses’ Health Study II. From blood samples collected in 1996–1999 a...
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| creator | Houghton, Serena C. Eliassen, A. Heather Zhang, Shumin M. Selhub, Jacob Rosner, Bernard A. Willett, Walter C. Hankinson, Susan E. |
| description | Purpose
We examined the association of plasma B-vitamins and metabolites, and related genetic variants, with risk of breast cancer among predominantly premenopausal women.
Methods
We conducted a nested case–control study within the Nurses’ Health Study II. From blood samples collected in 1996–1999 and follow-up through 2007, plasma measures were available for 610 cases and 1207 controls. Unconditional multivariable logistic regression was used to estimate relative risks (RR) of breast cancer and 95% confidence intervals (CIs). We examined whether associations varied by methylenetetrahydrofolate reductase (MTHFR) and dihydrofolate reductase polymorphisms, breast cancer risk factors, or tumor characteristics.
Results
Plasma vitamin B
12
was associated with a 64% higher risk of breast cancer comparing the highest versus lowest quintile (95% CI 1.17–2.29,
p
-trend = 0.02). Plasma folate (comparable RR = 1.18, 95% CI 0.84–1.66), pyridoxal 5′-phosphate (RR = 1.18, 95% CI 0.85–1.64), homocysteine (RR = 0.93, 95% CI 0.67–1.28), cysteine (RR = 1.14, 95% CI 0.81–1.62), and cysteinylglycine (RR = 0.93, 95% CI 0.66–1.31) were not associated with overall breast cancer risk. Folate was significantly positively associated with invasive and estrogen receptor-positive/progesterone receptor-positive breast cancer, and this association was suggestively stronger for bloods collected post-fortification. Several nutrient/breast cancer associations varied across subgroups defined by age, smoking, alcohol, multivitamin use, and MTHFR status (
p
-interaction |
| doi_str_mv | 10.1007/s10549-019-05223-x |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6551273</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2204042363</sourcerecordid><originalsourceid>FETCH-LOGICAL-c474t-7b968d1648cb162db49d4d574a02e33616ad6ff2e9f064f5d2e0be00426065543</originalsourceid><addsrcrecordid>eNp9kUtv1TAQhS1ERS-FP8ACWWLDxnT8vtkg0YqXVKksYMXCcpJJ65LYxU5K--_xJaUFFiwsWzrfHM_MIeQZh1ccwB4WDlo1DHg9WgjJrh-QDddWMiu4fUg2wI1lZgtmnzwu5QIAGgvNI7IvodGab9WGfP00-jJ5esSuwuynEAv1sacpIut8blOkE86-TWOYcZXmc6Q5lG80DbTN6MtMOx87zDREepOWeFafP9KE8QnZG_xY8OntfUC-vHv7-fgDOzl9__H4zQnrlFUzs21jtj03atu13Ii-VU2vem2VB4FSGm58b4ZBYDOAUYPuBUKLAEoYMForeUBer76XSzth32Gcsx_dZQ6Tzzcu-eD-VmI4d2fpytVqLqysBi9vDXL6vmCZ3RRKh-PoI6alOCHqornWwlT0xT_oRVpyrOPtKFWbkmZnKFaqy6mUjMNdMxzcLju3Zudqdu5Xdu66Fj3_c4y7kt9hVUCuQKnSbs33f__H9ieM6aU0</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2204042363</pqid></control><display><type>article</type><title>Plasma B-vitamins and one-carbon metabolites and the risk of breast cancer in younger women</title><source>SpringerLink Journals - AutoHoldings</source><creator>Houghton, Serena C. ; Eliassen, A. Heather ; Zhang, Shumin M. ; Selhub, Jacob ; Rosner, Bernard A. ; Willett, Walter C. ; Hankinson, Susan E.</creator><creatorcontrib>Houghton, Serena C. ; Eliassen, A. Heather ; Zhang, Shumin M. ; Selhub, Jacob ; Rosner, Bernard A. ; Willett, Walter C. ; Hankinson, Susan E.</creatorcontrib><description>Purpose
We examined the association of plasma B-vitamins and metabolites, and related genetic variants, with risk of breast cancer among predominantly premenopausal women.
Methods
We conducted a nested case–control study within the Nurses’ Health Study II. From blood samples collected in 1996–1999 and follow-up through 2007, plasma measures were available for 610 cases and 1207 controls. Unconditional multivariable logistic regression was used to estimate relative risks (RR) of breast cancer and 95% confidence intervals (CIs). We examined whether associations varied by methylenetetrahydrofolate reductase (MTHFR) and dihydrofolate reductase polymorphisms, breast cancer risk factors, or tumor characteristics.
Results
Plasma vitamin B
12
was associated with a 64% higher risk of breast cancer comparing the highest versus lowest quintile (95% CI 1.17–2.29,
p
-trend = 0.02). Plasma folate (comparable RR = 1.18, 95% CI 0.84–1.66), pyridoxal 5′-phosphate (RR = 1.18, 95% CI 0.85–1.64), homocysteine (RR = 0.93, 95% CI 0.67–1.28), cysteine (RR = 1.14, 95% CI 0.81–1.62), and cysteinylglycine (RR = 0.93, 95% CI 0.66–1.31) were not associated with overall breast cancer risk. Folate was significantly positively associated with invasive and estrogen receptor-positive/progesterone receptor-positive breast cancer, and this association was suggestively stronger for bloods collected post-fortification. Several nutrient/breast cancer associations varied across subgroups defined by age, smoking, alcohol, multivitamin use, and MTHFR status (
p
-interaction < 0.05).
Conclusions
Overall, plasma B-vitamins and metabolites were not associated with lower breast cancer risk. Plasma vitamin B-12 was positively associated with higher risk of overall breast cancer, and plasma folate was positively associated with risk of invasive breast cancer. Additionally, there may be associations in subgroups defined by related genetic variants, breast cancer risk factors, and tumor factors. Further studies in younger women and in the post-fortification era are needed to confirm these findings.</description><identifier>ISSN: 0167-6806</identifier><identifier>EISSN: 1573-7217</identifier><identifier>DOI: 10.1007/s10549-019-05223-x</identifier><identifier>PMID: 30955184</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Breast cancer ; Cancer research ; Dihydrofolate reductase ; Epidemiology ; Estrogen receptors ; Folic acid ; Genetic diversity ; Health risk assessment ; Homocysteine ; Hormone replacement therapy ; Invasiveness ; Medicine ; Medicine & Public Health ; Metabolites ; Methylenetetrahydrofolate reductase ; Oncology ; Progesterone ; Risk factors ; Smoking ; Vitamin B ; Vitamin B12 ; Vitamins</subject><ispartof>Breast cancer research and treatment, 2019-07, Vol.176 (1), p.191-203</ispartof><rights>Springer Science+Business Media, LLC, part of Springer Nature 2019</rights><rights>Breast Cancer Research and Treatment is a copyright of Springer, (2019). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-7b968d1648cb162db49d4d574a02e33616ad6ff2e9f064f5d2e0be00426065543</citedby><cites>FETCH-LOGICAL-c474t-7b968d1648cb162db49d4d574a02e33616ad6ff2e9f064f5d2e0be00426065543</cites><orcidid>0000-0001-8833-9065</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10549-019-05223-x$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10549-019-05223-x$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30955184$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Houghton, Serena C.</creatorcontrib><creatorcontrib>Eliassen, A. Heather</creatorcontrib><creatorcontrib>Zhang, Shumin M.</creatorcontrib><creatorcontrib>Selhub, Jacob</creatorcontrib><creatorcontrib>Rosner, Bernard A.</creatorcontrib><creatorcontrib>Willett, Walter C.</creatorcontrib><creatorcontrib>Hankinson, Susan E.</creatorcontrib><title>Plasma B-vitamins and one-carbon metabolites and the risk of breast cancer in younger women</title><title>Breast cancer research and treatment</title><addtitle>Breast Cancer Res Treat</addtitle><addtitle>Breast Cancer Res Treat</addtitle><description>Purpose
We examined the association of plasma B-vitamins and metabolites, and related genetic variants, with risk of breast cancer among predominantly premenopausal women.
Methods
We conducted a nested case–control study within the Nurses’ Health Study II. From blood samples collected in 1996–1999 and follow-up through 2007, plasma measures were available for 610 cases and 1207 controls. Unconditional multivariable logistic regression was used to estimate relative risks (RR) of breast cancer and 95% confidence intervals (CIs). We examined whether associations varied by methylenetetrahydrofolate reductase (MTHFR) and dihydrofolate reductase polymorphisms, breast cancer risk factors, or tumor characteristics.
Results
Plasma vitamin B
12
was associated with a 64% higher risk of breast cancer comparing the highest versus lowest quintile (95% CI 1.17–2.29,
p
-trend = 0.02). Plasma folate (comparable RR = 1.18, 95% CI 0.84–1.66), pyridoxal 5′-phosphate (RR = 1.18, 95% CI 0.85–1.64), homocysteine (RR = 0.93, 95% CI 0.67–1.28), cysteine (RR = 1.14, 95% CI 0.81–1.62), and cysteinylglycine (RR = 0.93, 95% CI 0.66–1.31) were not associated with overall breast cancer risk. Folate was significantly positively associated with invasive and estrogen receptor-positive/progesterone receptor-positive breast cancer, and this association was suggestively stronger for bloods collected post-fortification. Several nutrient/breast cancer associations varied across subgroups defined by age, smoking, alcohol, multivitamin use, and MTHFR status (
p
-interaction < 0.05).
Conclusions
Overall, plasma B-vitamins and metabolites were not associated with lower breast cancer risk. Plasma vitamin B-12 was positively associated with higher risk of overall breast cancer, and plasma folate was positively associated with risk of invasive breast cancer. Additionally, there may be associations in subgroups defined by related genetic variants, breast cancer risk factors, and tumor factors. Further studies in younger women and in the post-fortification era are needed to confirm these findings.</description><subject>Breast cancer</subject><subject>Cancer research</subject><subject>Dihydrofolate reductase</subject><subject>Epidemiology</subject><subject>Estrogen receptors</subject><subject>Folic acid</subject><subject>Genetic diversity</subject><subject>Health risk assessment</subject><subject>Homocysteine</subject><subject>Hormone replacement therapy</subject><subject>Invasiveness</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolites</subject><subject>Methylenetetrahydrofolate reductase</subject><subject>Oncology</subject><subject>Progesterone</subject><subject>Risk factors</subject><subject>Smoking</subject><subject>Vitamin B</subject><subject>Vitamin B12</subject><subject>Vitamins</subject><issn>0167-6806</issn><issn>1573-7217</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kUtv1TAQhS1ERS-FP8ACWWLDxnT8vtkg0YqXVKksYMXCcpJJ65LYxU5K--_xJaUFFiwsWzrfHM_MIeQZh1ccwB4WDlo1DHg9WgjJrh-QDddWMiu4fUg2wI1lZgtmnzwu5QIAGgvNI7IvodGab9WGfP00-jJ5esSuwuynEAv1sacpIut8blOkE86-TWOYcZXmc6Q5lG80DbTN6MtMOx87zDREepOWeFafP9KE8QnZG_xY8OntfUC-vHv7-fgDOzl9__H4zQnrlFUzs21jtj03atu13Ii-VU2vem2VB4FSGm58b4ZBYDOAUYPuBUKLAEoYMForeUBer76XSzth32Gcsx_dZQ6Tzzcu-eD-VmI4d2fpytVqLqysBi9vDXL6vmCZ3RRKh-PoI6alOCHqornWwlT0xT_oRVpyrOPtKFWbkmZnKFaqy6mUjMNdMxzcLju3Zudqdu5Xdu66Fj3_c4y7kt9hVUCuQKnSbs33f__H9ieM6aU0</recordid><startdate>20190701</startdate><enddate>20190701</enddate><creator>Houghton, Serena C.</creator><creator>Eliassen, A. Heather</creator><creator>Zhang, Shumin M.</creator><creator>Selhub, Jacob</creator><creator>Rosner, Bernard A.</creator><creator>Willett, Walter C.</creator><creator>Hankinson, Susan E.</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>K9-</scope><scope>K9.</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-8833-9065</orcidid></search><sort><creationdate>20190701</creationdate><title>Plasma B-vitamins and one-carbon metabolites and the risk of breast cancer in younger women</title><author>Houghton, Serena C. ; Eliassen, A. Heather ; Zhang, Shumin M. ; Selhub, Jacob ; Rosner, Bernard A. ; Willett, Walter C. ; Hankinson, Susan E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-7b968d1648cb162db49d4d574a02e33616ad6ff2e9f064f5d2e0be00426065543</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Breast cancer</topic><topic>Cancer research</topic><topic>Dihydrofolate reductase</topic><topic>Epidemiology</topic><topic>Estrogen receptors</topic><topic>Folic acid</topic><topic>Genetic diversity</topic><topic>Health risk assessment</topic><topic>Homocysteine</topic><topic>Hormone replacement therapy</topic><topic>Invasiveness</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metabolites</topic><topic>Methylenetetrahydrofolate reductase</topic><topic>Oncology</topic><topic>Progesterone</topic><topic>Risk factors</topic><topic>Smoking</topic><topic>Vitamin B</topic><topic>Vitamin B12</topic><topic>Vitamins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Houghton, Serena C.</creatorcontrib><creatorcontrib>Eliassen, A. Heather</creatorcontrib><creatorcontrib>Zhang, Shumin M.</creatorcontrib><creatorcontrib>Selhub, Jacob</creatorcontrib><creatorcontrib>Rosner, Bernard A.</creatorcontrib><creatorcontrib>Willett, Walter C.</creatorcontrib><creatorcontrib>Hankinson, Susan E.</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Breast cancer research and treatment</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Houghton, Serena C.</au><au>Eliassen, A. Heather</au><au>Zhang, Shumin M.</au><au>Selhub, Jacob</au><au>Rosner, Bernard A.</au><au>Willett, Walter C.</au><au>Hankinson, Susan E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Plasma B-vitamins and one-carbon metabolites and the risk of breast cancer in younger women</atitle><jtitle>Breast cancer research and treatment</jtitle><stitle>Breast Cancer Res Treat</stitle><addtitle>Breast Cancer Res Treat</addtitle><date>2019-07-01</date><risdate>2019</risdate><volume>176</volume><issue>1</issue><spage>191</spage><epage>203</epage><pages>191-203</pages><issn>0167-6806</issn><eissn>1573-7217</eissn><abstract>Purpose
We examined the association of plasma B-vitamins and metabolites, and related genetic variants, with risk of breast cancer among predominantly premenopausal women.
Methods
We conducted a nested case–control study within the Nurses’ Health Study II. From blood samples collected in 1996–1999 and follow-up through 2007, plasma measures were available for 610 cases and 1207 controls. Unconditional multivariable logistic regression was used to estimate relative risks (RR) of breast cancer and 95% confidence intervals (CIs). We examined whether associations varied by methylenetetrahydrofolate reductase (MTHFR) and dihydrofolate reductase polymorphisms, breast cancer risk factors, or tumor characteristics.
Results
Plasma vitamin B
12
was associated with a 64% higher risk of breast cancer comparing the highest versus lowest quintile (95% CI 1.17–2.29,
p
-trend = 0.02). Plasma folate (comparable RR = 1.18, 95% CI 0.84–1.66), pyridoxal 5′-phosphate (RR = 1.18, 95% CI 0.85–1.64), homocysteine (RR = 0.93, 95% CI 0.67–1.28), cysteine (RR = 1.14, 95% CI 0.81–1.62), and cysteinylglycine (RR = 0.93, 95% CI 0.66–1.31) were not associated with overall breast cancer risk. Folate was significantly positively associated with invasive and estrogen receptor-positive/progesterone receptor-positive breast cancer, and this association was suggestively stronger for bloods collected post-fortification. Several nutrient/breast cancer associations varied across subgroups defined by age, smoking, alcohol, multivitamin use, and MTHFR status (
p
-interaction < 0.05).
Conclusions
Overall, plasma B-vitamins and metabolites were not associated with lower breast cancer risk. Plasma vitamin B-12 was positively associated with higher risk of overall breast cancer, and plasma folate was positively associated with risk of invasive breast cancer. Additionally, there may be associations in subgroups defined by related genetic variants, breast cancer risk factors, and tumor factors. Further studies in younger women and in the post-fortification era are needed to confirm these findings.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>30955184</pmid><doi>10.1007/s10549-019-05223-x</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0001-8833-9065</orcidid><oa>free_for_read</oa></addata></record> |
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| source | SpringerLink Journals - AutoHoldings |
| subjects | Breast cancer Cancer research Dihydrofolate reductase Epidemiology Estrogen receptors Folic acid Genetic diversity Health risk assessment Homocysteine Hormone replacement therapy Invasiveness Medicine Medicine & Public Health Metabolites Methylenetetrahydrofolate reductase Oncology Progesterone Risk factors Smoking Vitamin B Vitamin B12 Vitamins |
| title | Plasma B-vitamins and one-carbon metabolites and the risk of breast cancer in younger women |
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