--- title: "Adiposity, inflammation, gene variants & breast cancer risk. | Sutter Health" description: "Findings confirm again that low penetrance genes involved in the inflammatory pathway may have a plausible causative role in post menopausal breast cancer." url: "https://www.sutterhealth.org/research/publications/adiposity-inflammation-gene-variants-breast-cancer-risk-1055312676" --- 1. [Home](https://www.sutterhealth.org/) / 2. [Research](https://www.sutterhealth.org/research) / 3. [Research publications](https://www.sutterhealth.org/research/publications) / 4. Adiposity, inflammation, gene variants & breast cancer risk. # Adiposity, inflammation, genetic variants and risk of post-menopausal breast cancer findings from a prospective-specimen-collection, retrospective-blinded-evaluation (PRoBE) design approach. Yan XS, Barnholtz-Sloan J, Chu X, Li L, Colonie R, Webster J, Smelser D, Patel N, Prichard J, & Stark A. _Springerplus. 2:638. doi: 10.1186/2193-1801-2-638. eCollection 2013._ 2013-11-27 ## Abstract Chronic internal inflammation secondary to adiposity is a risk factor for sporadic breast cancer and Post-Menopausal Breast Cancer (PMBC) is largely defined as such. Adiposity is one of the clinical criteria for the diagnosis of Metabolic Syndrome (MetS) and is a risk factor for PMBC. We examined SNPs of eight genes implicated in adiposity, inflammation and cell proliferation in a Prospective-specimen-collection, Retrospective-Blinded-Evaluation (PRoBE) design approach. A total of 180 cases and 732 age-matched controls were identified from the MyCode prospective biobank database and then linked to the Clinical Decision Information System, an enterprise-wide data warehouse, to retrieve clinico-demographic data. Samples were analyzed in a core laboratory where the personnel were masked to their status. Results from multivariate logistic regression yielded one SNP (rs2922126) in the GHSR as protective against PMBC among homozygotes for the minor allele (A/A) (OR = 0.4, 95% CI 0.18-.89, P-value = .02); homozygosity for the minor allele (C/C) of the SNP (rs889312) of the gene MAP3K1 was associated with the risk of PMBC (OR = 2.41, 95% CI 1.25-4.63 P-value = .008). Advanced age was protective against PMBC (OR = 0.98, 95% CI 0.95-0.99, P-value = .02). Family history of breast cancer (OR = 2.22, 95% CI 1.14-4.43. P = .02), HRT (OR = 3.35; 95% CI 2.15-5.21, P < .001), and MetS (OR = 14.83, 95% CI 5.63-39.08, P < .001) and interaction between HRT and MetS (OR = 39.38, 95% CI 15.71-98.70, P < .001) were associated with the risk of PMBC. We did not detected significant interactions between SNPs or between the SNPs and the clinico-demographic risk factors. Our study further confirms that MetS increases the risk of PMBC and argues in favor of reducing exposure to HRT. Our findings are another confirmation that low penetrance genes involved in the inflammatory pathway, i.e. MAP3KI gene, may have a plausible causative role in PMBC. Given the fact that genetic constitutionality of individuals cannot be changed, efforts should be focused on life style modification. [PubMed abstract](https://www.ncbi.nlm.nih.gov/pubmed/24340245) ![Xiaowei (Sherry) Yan, Ph.D.](https://dyn.mktgcdn.com/p/NTWox_hkmxIRiqJEc5PXKeBkfR_WMtpSQbEI4J69Xls/fit=crop,gravity=auto,dpr=2,width=188,height=250,quality=100) Xiaowei (Sherry) Yan, Ph.D. Principal investigator [View profile](https://www.sutterhealth.org/research/investigators/xiaowei-sherry-yan-phd-1049681042) ## Research topics - [Breast Cancer](https://www.sutterhealth.org/research-search-results?query=%22%5C%22Breast+Cancer%5C%22%22) - [All Cancer](https://www.sutterhealth.org/research-search-results?query=%22%5C%22All+Cancer%5C%22%22) - [Diabetes, Insulin Resistance and Metabolic Syndrome](https://www.sutterhealth.org/research-search-results?query=%22%5C%22Diabetes%2C+Insulin+Resistance+and+Metabolic+Syndrome%5C%22%22) - [Genetics](https://www.sutterhealth.org/research-search-results?query=%22%5C%22Genetics%5C%22%22) ## Related publications [View all publications](https://www.sutterhealth.org/research-search-results?verticalKey=research_publication) - Publication ### [Does the diagnosis of breast or ovarian cancer trigger referral to genetic counseling?](https://www.sutterhealth.org/research/publications/breast-ovarian-cancer-dx-trigger-genetic-counseling-referral-1055312651) Powell CB, Littell R, Hoodfar E, Sinclair F, Pressman A. Int J Gynecol Cancer. 23(3):431-6. doi: 10.1097/IGC.0b013e318280f2b4. 2013 Mar 01 - Publication ### [Higher absolute lymphocyte counts predict lower mortality from early-stage triple-negative breast cancer.](https://www.sutterhealth.org/research/publications/higher-lyphocyte-count-predict-lower-mortality-breast-ca-1055312328) Afghahi A, Purington N, Han SS, Desai M, Pierson E, Mathur MB, Seto T, Thompson CA, Rigdon J, Telli ML, Badve SS, Curtis C, West RB, Horst K, Gomez SL, Ford JM, Sledge GW, Kurian AW. Clin Cancer Res. pii: clincanres.1323.2017. doi: 10.1158/1078-0432.CCR-17-1323. \[Epub ahead of print\] 2018 Mar 26 - Publication ### [The Healthcare Systems Research Network (HCSRN) as an environment for dissemination and implementation research: a case study of developing a multi-site research study in precision medicine.](https://www.sutterhealth.org/research/publications/hcsrn-as-environment-for-implementation-research-1055312447) Rahm AK, Ladd I, Burnett-Hartman AN, Epstein MM, Lowery JT, Lu CY, Pawloski PA, Sharaf RN, Liang SY, Hunter JE. EGEMS (Wash DC). 7(1):16. doi: 10.5334/egems.283. 2019 Apr 12 - Publication ### [Breast cancer chemoprevention in primary care - assessing readiness for change.](https://www.sutterhealth.org/research/publications/breast-cancer-chemoprevention-in-primary-care-1055312742) Wang H, Snyder CF, Larson S, Vogel V, Kirchner HL, Sun H, Yan X. 24(6):283-288. Qual Prim Care. 2016 Nov 01 - Publication ### [Early diffusion of gene expression profiling in breast cancer patients associated with areas of high income inequality.](https://www.sutterhealth.org/research/publications/diffusion-gene-expression-profiling-breast-cancer-1055312821) Ponce NA, Ko M, Liang SY, Armstrong J, Toscano M, Chanfreau-Coffinier C, Haas JS. Health Aff (Millwood). 2015 Apr 1;34(4):609-15. doi: 10.1377/hlthaff.2014.1013. 2015 Apr 01 [View all publications](https://www.sutterhealth.org/research-search-results?verticalKey=research_publication) ```json {"@context":"https://schema.org","@type":"MedicalOrganization","name":"Sutter Health","@id":"https://www.sutterhealth.org/#medicalorganization","url":"https://www.sutterhealth.org","logo":"https://www.sutterhealth.org/static/images/sutter-health-logo.svg","address":{"@type":"PostalAddress","streetAddress":"2200 River Plaza Drive","addressLocality":"Sacramento","addressRegion":"CA","postalCode":"95833","addressCountry":"US"},"areaServed":{"@type":"AdministrativeArea","name":"California"},"sameAs":["https://www.facebook.com/SutterHealth","https://www.instagram.com/sutterhealth/","https://x.com/SutterHealth","https://www.youtube.com/sutterhealth","https://www.linkedin.com/company/sutter-health","https://en.wikipedia.org/wiki/Sutter_Health"]} ``` ```json {"@context":"https://schema.org","@type":"BreadcrumbList","@id":"https://www.sutterhealth.org/research/publications/adiposity-inflammation-gene-variants-breast-cancer-risk-1055312676#breadcrumblist","itemListElement":[{"@type":"ListItem","position":1,"name":"Home","item":"https://www.sutterhealth.org/"},{"@type":"ListItem","position":2,"name":"Research","item":"https://www.sutterhealth.org/research"},{"@type":"ListItem","position":3,"name":"Research publications","item":"https://www.sutterhealth.org/research/publications"},{"@type":"ListItem","position":4,"name":"Adiposity, inflammation, gene variants & breast cancer risk."}]} ``` ```json {"@context":"https://schema.org","@type":"MedicalScholarlyArticle","@id":"https://www.sutterhealth.org/research/publications/adiposity-inflammation-gene-variants-breast-cancer-risk-1055312676#medicalscholarlyarticle","name":"Adiposity, inflammation, genetic variants and risk of post-menopausal breast cancer findings from a prospective-specimen-collection, retrospective-blinded-evaluation (PRoBE) design approach.","headline":"Adiposity, inflammation, gene variants & breast cancer risk.","abstract":"Chronic internal inflammation secondary to adiposity is a risk factor for sporadic breast cancer and Post-Menopausal Breast Cancer (PMBC) is largely defined as such. Adiposity is one of the clinical criteria for the diagnosis of Metabolic Syndrome (MetS) and is a risk factor for PMBC. We examined SNPs of eight genes implicated in adiposity, inflammation and cell proliferation in a Prospective-specimen-collection, Retrospective-Blinded-Evaluation (PRoBE) design approach. A total of 180 cases and 732 age-matched controls were identified from the MyCode prospective biobank database and then linked to the Clinical Decision Information System, an enterprise-wide data warehouse, to retrieve clinico-demographic data. Samples were analyzed in a core laboratory where the personnel were masked to their status. Results from multivariate logistic regression yielded one SNP (rs2922126) in the GHSR as protective against PMBC among homozygotes for the minor allele (A/A) (OR = 0.4, 95% CI 0.18-.89, P-value = .02); homozygosity for the minor allele (C/C) of the SNP (rs889312) of the gene MAP3K1 was associated with the risk of PMBC (OR = 2.41, 95% CI 1.25-4.63 P-value = .008). Advanced age was protective against PMBC (OR = 0.98, 95% CI 0.95-0.99, P-value = .02). Family history of breast cancer (OR = 2.22, 95% CI 1.14-4.43. P = .02), HRT (OR = 3.35; 95% CI 2.15-5.21, P \u003c .001), and MetS (OR = 14.83, 95% CI 5.63-39.08, P \u003c .001) and interaction between HRT and MetS (OR = 39.38, 95% CI 15.71-98.70, P \u003c .001) were associated with the risk of PMBC. We did not detected significant interactions between SNPs or between the SNPs and the clinico-demographic risk factors. Our study further confirms that MetS increases the risk of PMBC and argues in favor of reducing exposure to HRT. Our findings are another confirmation that low penetrance genes involved in the inflammatory pathway, i.e. MAP3KI gene, may have a plausible causative role in PMBC. 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