Lipoprotein and metabolite associations to breast cancer risk in the HUNT2 study

Background: The aim of this study was to investigate if serum lipoprotein and metabolic profiles of healthy women can predict the risk of developing breast cancer in the future, and to gain a better understanding of the etiology of the disease. Methods: From a cohort of 70 000 participants within the Trondelag Health Study (HUNT study), we identified 1199 women who developed breast cancer within a 22 year follow-up period. Through a nested case-control study design, future breast cancer patients and matching controls (n = 2398) were analysed. Using nuclear magnetic resonance (NMR) spectroscopy, 28 metabolites and 112 lipoprotein subfractions were quantified from prediagnostic serum samples. Logistic regression was used to test metabolites and lipoprotein subfractions for associations with breast cancer risk and partial least-squares discriminant analysis (PLS-DA) models were built to predict future disease. Results: Among premenopausal women (554 cases) 14 lipoprotein subfractions were associated with long-term breast cancer risk. In specific, different subfractions of VLDL particles (in particular VLDL-2, VLDL-3 and VLDL-4) were inversely associated with breast cancer. For total VLDL: apolipoprotein B, cholesterol, free cholesterol and phospholipids were inversely associated with premenopausal breast cancer risk, and in addition total and HDL-4 triglycerides. No significant association was found in postmenopausal women. Conclusions: We identified several associations between lipoprotein subfractions and long-term risk of breast cancer in premenopausal women. Inverse associations between several VLDL subfractions and breast cancer risk were found, revealing an altered metabolism in the endogenous lipid pathway many years prior to a breast cancer diagnosis.

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Assessment of Breast Cancer Risk Based on Mammary Gland Volume Measured with CT

Breast Cancer Basic and Clinical Research ◽

10.4137/bcbcr.s5248 ◽

2010 ◽

Vol 4 ◽

pp. BCBCR.S5248 ◽

Cited By ~ 3

Author(s):

Megumi Kuchiki ◽

Takaaki Hosoya ◽

Akira Fukao

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Cancer Patients ◽

Odds Ratio ◽

Premenopausal Women ◽

Breast Cancer Patients ◽

History Of ◽

The Relationship

We investigated the relationship between mammary gland volume (MGV) of the breast as measured with three-dimensional chest computed tomography (CT) and breast cancer risk. Univariate analysis was used to assess the relationship between MGV and known risk factors in 427 healthy women. A case control study (97 cases and 194 controls) was conducted to assess breast cancer risk. MGV was significantly smaller for postmenopausal women than for premenopausal women, and was significantly larger for women with a family history of breast cancer than for women without. MGV, body mass index (BMI), and rate of family history of breast cancer were significantly higher among breast cancer patients than among healthy women, and number of deliveries was significantly lower among breast cancer patients. In postmenopausal women, age at menarche was significantly younger for breast cancer patients. MGV correlated well with breast cancer risk factors. The highest odds ratio was 4.9 for premenopausal women with the largest MGV. Regardless of menopausal status, the greater the MGV, the higher the odds ratio. Our results constitute the first reliable data on the relationship between MGV and breast cancer obtained through exact volume analysis.

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Insulin-like growth factor-I, its binding proteins (IGFBP-1 and IGFBP-3), and growth hormone and breast cancer risk in The Nurses Health Study II

Endocrine Related Cancer ◽

10.1677/erc.1.01149 ◽

2006 ◽

Vol 13 (2) ◽

pp. 583-592 ◽

Cited By ~ 99

Author(s):

Eva S Schernhammer ◽

Jeff M Holly ◽

David J Hunter ◽

Michael N Pollak ◽

Susan E Hankinson

Keyword(s):

Breast Cancer ◽

Growth Hormone ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Premenopausal Women ◽

Health Study ◽

Blood Collection ◽

Factor I ◽

Igf I ◽

Igfbp 3

Earlier data suggest that the relationship between circulating insulin-like growth factor I (IGF-I) levels and breast cancer risk differs according to menopausal status. We evaluated the association between IGF levels as well as the primary regulator of IGF-I production, growth hormone (GH), and breast cancer risk in the Nurses’ Health Study II (NHS II) cohort, a large cohort of primarily premenopausal women. We conducted a case-control study nested within the prospective NHS II cohort. Plasma concentrations of IGF-I, IGF binding protein (IGFBP)-3, IGFBP-1, and GH were measured in blood samples collected between 1996 and 1999. Totally 317 women were identified who had a diagnosis of invasive or in situ breast cancer between the date of blood collection and June 1 2003; 75% of these women were premenopausal at blood collection. To each of the 317 women, two controls were age-matched for a total of 634 controls. We used conditional logistic regression models to estimate the relative risk of breast cancer. Overall, plasma IGF-I, IGFBP-1, IGFBP-3, and GH levels were not associated with breast cancer risk (relative risks, top vs bottom quartile; IGF-I, 0.98, 95% confidence interval (CI), 0.69–1.39; IGFBP-1, 0.95, 95% CI, 0.63–1.41; IGFBP-3, 1.10, 95% CI, 0.78–1.54; GH, 1.09, 95% CI, 0.82–1.46). These risks were similar for premenopausal women of age 45 years or less. Further adjustment for additional breast cancer risk factors did not change these estimates. In conclusion, circulating IGF-I, IGFBP-1, IGFBP-3, and GH levels appear to have no important association with breast cancer risk in a large cohort of premenopausal women.

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Circulating amino acids and amino acid-related metabolites and risk of breast cancer among predominantly premenopausal women

npj Breast Cancer ◽

10.1038/s41523-021-00262-4 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Oana A. Zeleznik ◽

Raji Balasubramanian ◽

Yibai Zhao ◽

Lisa Frueh ◽

Sarah Jeanfavre ◽

...

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

Amino Acids ◽

Amino Acid ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Kynurenic Acid ◽

Conditional Logistic Regression ◽

Premenopausal Women ◽

Health Study

AbstractKnown modifiable risk factors account for a small fraction of premenopausal breast cancers. We investigated associations between pre-diagnostic circulating amino acid and amino acid-related metabolites (N = 207) and risk of breast cancer among predominantly premenopausal women of the Nurses’ Health Study II using conditional logistic regression (1057 cases, 1057 controls) and multivariable analyses evaluating all metabolites jointly. Eleven metabolites were associated with breast cancer risk (q-value < 0.2). Seven metabolites remained associated after adjustment for established risk factors (p-value < 0.05) and were selected by at least one multivariable modeling approach: higher levels of 2-aminohippuric acid, kynurenic acid, piperine (all three with q-value < 0.2), DMGV and phenylacetylglutamine were associated with lower breast cancer risk (e.g., piperine: ORadjusted (95%CI) = 0.84 (0.77–0.92)) while higher levels of creatine and C40:7 phosphatidylethanolamine (PE) plasmalogen were associated with increased breast cancer risk (e.g., C40:7 PE plasmalogen: ORadjusted (95%CI) = 1.11 (1.01–1.22)). Five amino acids and amino acid-related metabolites (2-aminohippuric acid, DMGV, kynurenic acid, phenylacetylglutamine, and piperine) were inversely associated, while one amino acid and a phospholipid (creatine and C40:7 PE plasmalogen) were positively associated with breast cancer risk among predominately premenopausal women, independent of established breast cancer risk factors.

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Risk Factors for Premenopausal Breast Cancer in Bangladesh

International Journal of Breast Cancer ◽

10.1155/2015/612042 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 2

Author(s):

Javaid Iqbal ◽

Tahmina Ferdousy ◽

Rahela Dipi ◽

Reza Salim ◽

Wei Wu ◽

...

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Premenopausal Women ◽

Breast Cancer Diagnosis ◽

Age At Menarche ◽

Premenopausal Breast Cancer ◽

Factors Associated ◽

History Of

Background. The incidence of premenopausal breast cancer is rising throughout South Asia. Our objective was to determine the role of risk factors associated with Westernization for premenopausal breast cancer in Bangladesh.Methods. We conducted a matched case-control study between January 1, 2007, and December 31, 2010, at four hospitals in Bangladesh. Cases were premenopausal women diagnosed with invasive breast cancer. Controls were premenopausal women with no personal history of breast cancer. Logistic regression was used to calculate the odds ratios (OR) for breast cancer.Results. We identified 129 age-matched pairs. The mean age of breast cancer diagnosis was 37.5 years. Each year decrease in the age of menarche significantly increased the risk of breast cancer (OR = 1.67, 95% CI 1.09–2.56,P=0.02). The risk was also increased with a current body mass index of ≥25 kg/m2(OR = 5.24, 95% CI 1.10–24.9,P=0.04). Age at first childbirth, parity, and breastfeeding were not significantly associated with premenopausal breast cancer risk (P>0.05).Conclusions. Age at menarche and adult weight gain were associated with premenopausal breast cancer risk. Other factors associated with Westernization may not be relevant to premenopausal breast cancer risk in Bangladesh.

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Changes in epithelial proportions and transcriptional state underlie major premenopausal breast cancer risks

10.1101/430611 ◽

2018 ◽

Cited By ~ 3

Author(s):

Lyndsay M. Murrow ◽

Robert J. Weber ◽

Joseph A. Caruso ◽

Christopher S. McGinnis ◽

Kiet Phong ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Single Cell Analysis ◽

Transcriptional Response ◽

High Body Mass Index ◽

Premenopausal Women ◽

Premenopausal Breast Cancer ◽

Cell State ◽

State Affect

AbstractThe human breast undergoes lifelong remodeling in response to estrogen and progesterone, but hormone exposure also increases breast cancer risk. Here, we use single-cell analysis to identify distinct mechanisms through which breast composition and cell state affect hormone signaling. We show that prior pregnancy reduces the transcriptional response of hormone-responsive (HR+) epithelial cells, whereas high body mass index (BMI) reduces overall HR+ cell proportions. These distinct changes both impact neighboring cells by effectively reducing the magnitude of paracrine signals originating from HR+ cells. Because pregnancy and high BMI are known to protect against hormone-dependent breast cancer in premenopausal women, our findings directly link breast cancer risk with person-to-person heterogeneity in hormone responsiveness. More broadly, our findings illustrate how cell proportions and cell state can collectively impact cell communities through the action of cell-to-cell signaling networks.

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