Skip to main content
Top
Published in: Breast Cancer Research and Treatment 3/2011

01-08-2011 | Epidemiology

Urinary cadmium and mammographic density in premenopausal women

Authors: Scott V. Adams, Polly A. Newcomb, Martin M. Shafer, Charlotte Atkinson, Erin J. Aiello Bowles, Katherine M. Newton, Johanna W. Lampe

Published in: Breast Cancer Research and Treatment | Issue 3/2011

Login to get access

Abstract

Mammographic density (MD), a strong marker of breast cancer risk, is influenced by genetic, environmental, and hormonal factors. Cadmium, a persistent and widespread environmental pollutant, has been associated with risk of breast cancer, and laboratory evidence suggests cadmium is a carcinogen in the breast. We investigated the hypothesis that cadmium exposure is associated with higher MD. In a cross-sectional study of MD and urinary cadmium concentration, percentage MD (MD%) and Breast Imaging-Reporting and Data Systems (BI-RADS®) density category were determined from screening mammograms of 190 premenopausal women ages 40–45 years. Women completed a health questionnaire, and the cadmium content of spot urine samples was measured with inductively coupled plasma mass spectrometry and corrected for urine creatinine. Urinary cadmium concentrations are thought to reflect exposure to cadmium during a period of 20–30 years. Multivariable linear regression and logistic regression were used to estimate the strength of association between urinary cadmium and mammographic breast density. Adjusted mean MD% among women in the upper tertile of creatinine-corrected urinary cadmium was 4.6% higher (95% CI: –2.3 to 11.6%) than in women in the lowest cadmium tertile. Each twofold increase in urinary cadmium was associated with higher odds of MD% in the upper tertile (OR: 1.29, 95% CI: 0.82–2.02) or a BI-RADS category rating of “extremely dense” (OR: 1.75, 95% CI: 1.14–2.70). Stronger associations were observed among nulliparous women, and current or former smokers. Exposure to cadmium may be associated with increased breast density in premenopausal women.
Literature
1.
go back to reference McCormack VA, dos Santos Silva I (2006) Breast density and parenchymal patterns as markers of breast cancer risk: a meta-analysis. Cancer Epidemiol Biomarkers Prev 15(6):1159–1169PubMedCrossRef McCormack VA, dos Santos Silva I (2006) Breast density and parenchymal patterns as markers of breast cancer risk: a meta-analysis. Cancer Epidemiol Biomarkers Prev 15(6):1159–1169PubMedCrossRef
2.
go back to reference Martin LJ, Boyd NF (2008) Mammographic density. Potential mechanisms of breast cancer risk associated with mammographic density: hypotheses based on epidemiological evidence. Breast Cancer Res 10(1):201PubMedCrossRef Martin LJ, Boyd NF (2008) Mammographic density. Potential mechanisms of breast cancer risk associated with mammographic density: hypotheses based on epidemiological evidence. Breast Cancer Res 10(1):201PubMedCrossRef
3.
go back to reference Boyd NF, Rommens JM, Vogt K, Lee V, Hopper JL, Yaffe MJ, Paterson AD (2005) Mammographic breast density as an intermediate phenotype for breast cancer. Lancet Oncol 6(10):798–808PubMedCrossRef Boyd NF, Rommens JM, Vogt K, Lee V, Hopper JL, Yaffe MJ, Paterson AD (2005) Mammographic breast density as an intermediate phenotype for breast cancer. Lancet Oncol 6(10):798–808PubMedCrossRef
4.
go back to reference Tamimi RM, Byrne C, Colditz GA, Hankinson SE (2007) Endogenous hormone levels, mammographic density, and subsequent risk of breast cancer in postmenopausal women. J Natl Cancer Inst 99(15):1178–1187PubMedCrossRef Tamimi RM, Byrne C, Colditz GA, Hankinson SE (2007) Endogenous hormone levels, mammographic density, and subsequent risk of breast cancer in postmenopausal women. J Natl Cancer Inst 99(15):1178–1187PubMedCrossRef
5.
go back to reference Yong M, Atkinson C, Newton KM, Aiello Bowles EJ, Stanczyk FZ, Westerlind KC, Holt VL, Schwartz SM, Leisenring WM, Lampe JW (2009) Associations between endogenous sex hormone levels and mammographic and bone densities in premenopausal women. Cancer Causes Control 20(7):1039–1053PubMedCrossRef Yong M, Atkinson C, Newton KM, Aiello Bowles EJ, Stanczyk FZ, Westerlind KC, Holt VL, Schwartz SM, Leisenring WM, Lampe JW (2009) Associations between endogenous sex hormone levels and mammographic and bone densities in premenopausal women. Cancer Causes Control 20(7):1039–1053PubMedCrossRef
6.
go back to reference Verheus M, Peeters PH, van Noord PA, van der Schouw YT, Grobbee DE, van Gils CH (2007) No relationship between circulating levels of sex steroids and mammographic breast density: the prospect-epic cohort. Breast Cancer Res 9(4):R53PubMedCrossRef Verheus M, Peeters PH, van Noord PA, van der Schouw YT, Grobbee DE, van Gils CH (2007) No relationship between circulating levels of sex steroids and mammographic breast density: the prospect-epic cohort. Breast Cancer Res 9(4):R53PubMedCrossRef
7.
go back to reference Martin LJ, Minkin S, Boyd NF (2009) Hormone therapy, mammographic density, and breast cancer risk. Maturitas 64(1):20–26PubMedCrossRef Martin LJ, Minkin S, Boyd NF (2009) Hormone therapy, mammographic density, and breast cancer risk. Maturitas 64(1):20–26PubMedCrossRef
8.
go back to reference Butler LM, Gold EB, Conroy SM, Crandall CJ, Greendale GA, Oestreicher N, Quesenberry CP Jr, Habel LA (2010) Active, but not passive cigarette smoking was inversely associated with mammographic density. Cancer Causes Control 21(2):301–311PubMedCrossRef Butler LM, Gold EB, Conroy SM, Crandall CJ, Greendale GA, Oestreicher N, Quesenberry CP Jr, Habel LA (2010) Active, but not passive cigarette smoking was inversely associated with mammographic density. Cancer Causes Control 21(2):301–311PubMedCrossRef
9.
go back to reference Maskarinec G, Takata Y, Pagano I, Lurie G, Wilkens LR, Kolonel LN (2006) Alcohol consumption and mammographic density in a multiethnic population. Int J Cancer 118(10):2579–2583PubMedCrossRef Maskarinec G, Takata Y, Pagano I, Lurie G, Wilkens LR, Kolonel LN (2006) Alcohol consumption and mammographic density in a multiethnic population. Int J Cancer 118(10):2579–2583PubMedCrossRef
10.
go back to reference Boyd NF, Greenberg C, Lockwood G, Little L, Martin L, Byng J, Yaffe M, Tritchler D (1997) Effects at two years of a low-fat, high-carbohydrate diet on radiologic features of the breast: results from a randomized trial. Canadian diet and breast cancer prevention study group. J Natl Cancer Inst 89(7):488–496PubMedCrossRef Boyd NF, Greenberg C, Lockwood G, Little L, Martin L, Byng J, Yaffe M, Tritchler D (1997) Effects at two years of a low-fat, high-carbohydrate diet on radiologic features of the breast: results from a randomized trial. Canadian diet and breast cancer prevention study group. J Natl Cancer Inst 89(7):488–496PubMedCrossRef
11.
go back to reference Elinder CG (1992) Cadmium as an environmental hazard. IARC Sci Publ (118):123–132 Elinder CG (1992) Cadmium as an environmental hazard. IARC Sci Publ (118):123–132
12.
go back to reference Jarup L, Akesson A (2009) Current status of cadmium as an environmental health problem. Toxicol Appl Pharmacol 238(3):201–208PubMedCrossRef Jarup L, Akesson A (2009) Current status of cadmium as an environmental health problem. Toxicol Appl Pharmacol 238(3):201–208PubMedCrossRef
13.
go back to reference Satarug S, Baker JR, Urbenjapol S, Haswell-Elkins M, Reilly PE, Williams DJ, Moore MR (2003) A global perspective on cadmium pollution and toxicity in non-occupationally exposed population. Toxicol Lett 137(1–2):65–83PubMedCrossRef Satarug S, Baker JR, Urbenjapol S, Haswell-Elkins M, Reilly PE, Williams DJ, Moore MR (2003) A global perspective on cadmium pollution and toxicity in non-occupationally exposed population. Toxicol Lett 137(1–2):65–83PubMedCrossRef
14.
go back to reference Olsson IM, Eriksson J, Oborn I, Skerfving S, Oskarsson A (2005) Cadmium in food production systems: a health risk for sensitive population groups. Ambio 34(4–5):344–351PubMed Olsson IM, Eriksson J, Oborn I, Skerfving S, Oskarsson A (2005) Cadmium in food production systems: a health risk for sensitive population groups. Ambio 34(4–5):344–351PubMed
15.
go back to reference McElroy JA, Shafer MM, Trentham-Dietz A, Hampton JM, Newcomb PA (2006) Cadmium exposure and breast cancer risk. J Natl Cancer Inst 98(12):869–873PubMedCrossRef McElroy JA, Shafer MM, Trentham-Dietz A, Hampton JM, Newcomb PA (2006) Cadmium exposure and breast cancer risk. J Natl Cancer Inst 98(12):869–873PubMedCrossRef
16.
go back to reference Nawrot T, Plusquin M, Hogervorst J, Roels HA, Celis H, Thijs L, Vangronsveld J, Van Hecke E, Staessen JA (2006) Environmental exposure to cadmium and risk of cancer: a prospective population-based study. Lancet Oncol 7(2):119–126PubMedCrossRef Nawrot T, Plusquin M, Hogervorst J, Roels HA, Celis H, Thijs L, Vangronsveld J, Van Hecke E, Staessen JA (2006) Environmental exposure to cadmium and risk of cancer: a prospective population-based study. Lancet Oncol 7(2):119–126PubMedCrossRef
17.
go back to reference Cantor KP, Stewart PA, Brinton LA, Dosemeci M (1995) Occupational exposures and female breast cancer mortality in the United States. J Occup Environ Med 37(3):336–348PubMedCrossRef Cantor KP, Stewart PA, Brinton LA, Dosemeci M (1995) Occupational exposures and female breast cancer mortality in the United States. J Occup Environ Med 37(3):336–348PubMedCrossRef
18.
go back to reference Akesson A, Julin B, Wolk A (2008) Long-term dietary cadmium intake and postmenopausal endometrial cancer incidence: a population-based prospective cohort study. Cancer Res 68(15):6435–6441PubMedCrossRef Akesson A, Julin B, Wolk A (2008) Long-term dietary cadmium intake and postmenopausal endometrial cancer incidence: a population-based prospective cohort study. Cancer Res 68(15):6435–6441PubMedCrossRef
19.
go back to reference Johnson MD, Kenney N, Stoica A, Hilakivi-Clarke L, Singh B, Chepko G, Clarke R, Sholler PF, Lirio AA, Foss C, Reiter R, Trock B, Paik S, Martin MB (2003) Cadmium mimics the in vivo effects of estrogen in the uterus and mammary gland. Nat Med 9(8):1081–1084PubMedCrossRef Johnson MD, Kenney N, Stoica A, Hilakivi-Clarke L, Singh B, Chepko G, Clarke R, Sholler PF, Lirio AA, Foss C, Reiter R, Trock B, Paik S, Martin MB (2003) Cadmium mimics the in vivo effects of estrogen in the uterus and mammary gland. Nat Med 9(8):1081–1084PubMedCrossRef
20.
go back to reference Hofer N, Diel P, Wittsiepe J, Wilhelm M, Degen GH (2009) Dose- and route-dependent hormonal activity of the metalloestrogen cadmium in the rat uterus. Toxicol Lett 191(2–3):123–131PubMedCrossRef Hofer N, Diel P, Wittsiepe J, Wilhelm M, Degen GH (2009) Dose- and route-dependent hormonal activity of the metalloestrogen cadmium in the rat uterus. Toxicol Lett 191(2–3):123–131PubMedCrossRef
21.
go back to reference Martin BM, Reiter R, Pham T, Avellanet YR, Camara J, Lahm M, Pentecost E, Pratap K, Gilmore BA, Diverakar S, Dagata RS, Bull JL, Stoica A (2003) Estrogen-like activity of metals in mcf-7 breast cancer cells. Endocrinology 144:2425–2436PubMedCrossRef Martin BM, Reiter R, Pham T, Avellanet YR, Camara J, Lahm M, Pentecost E, Pratap K, Gilmore BA, Diverakar S, Dagata RS, Bull JL, Stoica A (2003) Estrogen-like activity of metals in mcf-7 breast cancer cells. Endocrinology 144:2425–2436PubMedCrossRef
22.
go back to reference Stoica A, Katzenellenbogen BS, Martin MB (2000) Activation of estrogen receptor-alpha by the heavy metal cadmium. Mol Endocrinol 14(4):545–553PubMedCrossRef Stoica A, Katzenellenbogen BS, Martin MB (2000) Activation of estrogen receptor-alpha by the heavy metal cadmium. Mol Endocrinol 14(4):545–553PubMedCrossRef
23.
go back to reference Brama M, Gnessi L, Basciani S, Cerulli N, Politi L, Spera G, Mariani S, Cherubini S, d’Abusco AS, Scandurra R, Migliaccio S (2007) Cadmium induces mitogenic signaling in breast cancer cell by an eralpha-dependent mechanism. Mol Cell Endocrinol 264(1–2):102–108PubMedCrossRef Brama M, Gnessi L, Basciani S, Cerulli N, Politi L, Spera G, Mariani S, Cherubini S, d’Abusco AS, Scandurra R, Migliaccio S (2007) Cadmium induces mitogenic signaling in breast cancer cell by an eralpha-dependent mechanism. Mol Cell Endocrinol 264(1–2):102–108PubMedCrossRef
25.
go back to reference Benbrahim-Tallaa L, Tokar EJ, Diwan BA, Dill AL, Coppin JF, Waalkes MP (2009) Cadmium malignantly transforms normal human breast epithelial cells into a basal-like phenotype. Environ Health Perspect 117(12):1847–1852PubMedCrossRef Benbrahim-Tallaa L, Tokar EJ, Diwan BA, Dill AL, Coppin JF, Waalkes MP (2009) Cadmium malignantly transforms normal human breast epithelial cells into a basal-like phenotype. Environ Health Perspect 117(12):1847–1852PubMedCrossRef
26.
go back to reference Liu J, Qu W, Kadiiska MB (2009) Role of oxidative stress in cadmium toxicity and carcinogenesis. Toxicol Appl Pharmacol 238(3):209–214PubMedCrossRef Liu J, Qu W, Kadiiska MB (2009) Role of oxidative stress in cadmium toxicity and carcinogenesis. Toxicol Appl Pharmacol 238(3):209–214PubMedCrossRef
27.
go back to reference Boyd NF, Connelly P, Byng J, Yaffe M, Draper H, Little L, Jones D, Martin LJ, Lockwood G, Tritchler D (1995) Plasma lipids, lipoproteins, and mammographic densities. Cancer Epidemiol Biomarkers Prev 4(7):727–733PubMed Boyd NF, Connelly P, Byng J, Yaffe M, Draper H, Little L, Jones D, Martin LJ, Lockwood G, Tritchler D (1995) Plasma lipids, lipoproteins, and mammographic densities. Cancer Epidemiol Biomarkers Prev 4(7):727–733PubMed
28.
go back to reference Hong CC, Tang BK, Rao V, Agarwal S, Martin L, Tritchler D, Yaffe M, Boyd NF (2004) Cytochrome p450 1a2 (cyp1a2) activity, mammographic density, and oxidative stress: a cross-sectional study. Breast Cancer Res 6(4):R338–R351PubMedCrossRef Hong CC, Tang BK, Rao V, Agarwal S, Martin L, Tritchler D, Yaffe M, Boyd NF (2004) Cytochrome p450 1a2 (cyp1a2) activity, mammographic density, and oxidative stress: a cross-sectional study. Breast Cancer Res 6(4):R338–R351PubMedCrossRef
29.
go back to reference Boyd NF, McGuire V (1990) Evidence of lipid peroxidation in premenopausal women with mammographic dysplasia. Cancer Lett 50(1):31–37PubMedCrossRef Boyd NF, McGuire V (1990) Evidence of lipid peroxidation in premenopausal women with mammographic dysplasia. Cancer Lett 50(1):31–37PubMedCrossRef
30.
go back to reference Atkinson C, Newton KM, Aiello Bowles EJ, Lehman CD, Stanczyk FZ, Westerlind KC, Li L, Lampe JW (2009) Daidzein-metabolizing phenotypes in relation to mammographic breast density among premenopausal women in the United States. Breast Cancer Res Treat 116(3):587–594PubMedCrossRef Atkinson C, Newton KM, Aiello Bowles EJ, Lehman CD, Stanczyk FZ, Westerlind KC, Li L, Lampe JW (2009) Daidzein-metabolizing phenotypes in relation to mammographic breast density among premenopausal women in the United States. Breast Cancer Res Treat 116(3):587–594PubMedCrossRef
31.
go back to reference Atkinson C, Newton KM, Bowles EJ, Yong M, Lampe JW (2008) Demographic, anthropometric, and lifestyle factors and dietary intakes in relation to daidzein-metabolizing phenotypes among premenopausal women in the United States. Am J Clin Nutr 87(3):679–687PubMed Atkinson C, Newton KM, Bowles EJ, Yong M, Lampe JW (2008) Demographic, anthropometric, and lifestyle factors and dietary intakes in relation to daidzein-metabolizing phenotypes among premenopausal women in the United States. Am J Clin Nutr 87(3):679–687PubMed
32.
go back to reference Boyd NF, Byng JW, Jong RA, Fishell EK, Little LE, Miller AB, Lockwood GA, Tritchler DL, Yaffe MJ (1995) Quantitative classification of mammographic densities and breast cancer risk: results from the Canadian national breast screening study. J Natl Cancer Inst 87(9):670–675PubMedCrossRef Boyd NF, Byng JW, Jong RA, Fishell EK, Little LE, Miller AB, Lockwood GA, Tritchler DL, Yaffe MJ (1995) Quantitative classification of mammographic densities and breast cancer risk: results from the Canadian national breast screening study. J Natl Cancer Inst 87(9):670–675PubMedCrossRef
33.
go back to reference McElroy JA, Shafer MM, Hampton JM, Newcomb PA (2007) Predictors of urinary cadmium levels in adult females. Sci Total Environ 382(2–3):214–223PubMedCrossRef McElroy JA, Shafer MM, Hampton JM, Newcomb PA (2007) Predictors of urinary cadmium levels in adult females. Sci Total Environ 382(2–3):214–223PubMedCrossRef
34.
35.
go back to reference Paschal DC, Burt V, Caudill SP, Gunter EW, Pirkle JL, Sampson EJ, Miller DT, Jackson RJ (2000) Exposure of the U.S. population aged 6 years and older to cadmium: 1988–1994. Arch Environ Contam Toxicol 38(3):377–383PubMedCrossRef Paschal DC, Burt V, Caudill SP, Gunter EW, Pirkle JL, Sampson EJ, Miller DT, Jackson RJ (2000) Exposure of the U.S. population aged 6 years and older to cadmium: 1988–1994. Arch Environ Contam Toxicol 38(3):377–383PubMedCrossRef
36.
go back to reference Suwazono Y, Akesson A, Alfven T, Jarup L, Vahter M (2005) Creatinine versus specific gravity-adjusted urinary cadmium concentrations. Biomarkers 10(2–3):117–126PubMedCrossRef Suwazono Y, Akesson A, Alfven T, Jarup L, Vahter M (2005) Creatinine versus specific gravity-adjusted urinary cadmium concentrations. Biomarkers 10(2–3):117–126PubMedCrossRef
37.
go back to reference Boyd N, Martin L, Chavez S, Gunasekara A, Salleh A, Melnichouk O, Yaffe M, Friedenreich C, Minkin S, Bronskill M (2009) Breast-tissue composition and other risk factors for breast cancer in young women: a cross-sectional study. Lancet Oncol 10(6):569–580PubMedCrossRef Boyd N, Martin L, Chavez S, Gunasekara A, Salleh A, Melnichouk O, Yaffe M, Friedenreich C, Minkin S, Bronskill M (2009) Breast-tissue composition and other risk factors for breast cancer in young women: a cross-sectional study. Lancet Oncol 10(6):569–580PubMedCrossRef
38.
go back to reference Bremnes Y, Ursin G, Bjurstam N, Gram IT (2007) Different measures of smoking exposure and mammographic density in postmenopausal Norwegian women: a cross-sectional study. Breast Cancer Res 9(5):R73PubMedCrossRef Bremnes Y, Ursin G, Bjurstam N, Gram IT (2007) Different measures of smoking exposure and mammographic density in postmenopausal Norwegian women: a cross-sectional study. Breast Cancer Res 9(5):R73PubMedCrossRef
39.
go back to reference Boyd NF, Stone J, Martin LJ, Jong R, Fishell E, Yaffe M, Hammond G, Minkin S (2002) The association of breast mitogens with mammographic densities. Br J Cancer 87(8):876–882PubMedCrossRef Boyd NF, Stone J, Martin LJ, Jong R, Fishell E, Yaffe M, Hammond G, Minkin S (2002) The association of breast mitogens with mammographic densities. Br J Cancer 87(8):876–882PubMedCrossRef
40.
go back to reference Walker K, Fletcher O, Johnson N, Coupland B, McCormack VA, Folkerd E, Gibson L, Hillier SG, Holly JM, Moss S, Dowsett M, Peto J, dos Santos Silva I (2009) Premenopausal mammographic density in relation to cyclic variations in endogenous sex hormone levels, prolactin, and insulin-like growth factors. Cancer Res 69(16):6490–6499PubMedCrossRef Walker K, Fletcher O, Johnson N, Coupland B, McCormack VA, Folkerd E, Gibson L, Hillier SG, Holly JM, Moss S, Dowsett M, Peto J, dos Santos Silva I (2009) Premenopausal mammographic density in relation to cyclic variations in endogenous sex hormone levels, prolactin, and insulin-like growth factors. Cancer Res 69(16):6490–6499PubMedCrossRef
41.
go back to reference Bremnes Y, Ursin G, Bjurstam N, Rinaldi S, Kaaks R, Gram IT (2007) Insulin-like growth factor and mammographic density in postmenopausal Norwegian women. Cancer Epidemiol Biomarkers Prev 16(1):57–62PubMedCrossRef Bremnes Y, Ursin G, Bjurstam N, Rinaldi S, Kaaks R, Gram IT (2007) Insulin-like growth factor and mammographic density in postmenopausal Norwegian women. Cancer Epidemiol Biomarkers Prev 16(1):57–62PubMedCrossRef
42.
go back to reference Iavicoli I, Fontana L, Bergamaschi A (2009) The effects of metals as endocrine disruptors. J Toxicol Environ Health B Crit Rev 12(3):206–223PubMedCrossRef Iavicoli I, Fontana L, Bergamaschi A (2009) The effects of metals as endocrine disruptors. J Toxicol Environ Health B Crit Rev 12(3):206–223PubMedCrossRef
43.
go back to reference Rosner B, Colditz GA (1996) Nurses’ health study: log-incidence mathematical model of breast cancer incidence. J Natl Cancer Inst 88(6):359–364PubMedCrossRef Rosner B, Colditz GA (1996) Nurses’ health study: log-incidence mathematical model of breast cancer incidence. J Natl Cancer Inst 88(6):359–364PubMedCrossRef
Metadata
Title
Urinary cadmium and mammographic density in premenopausal women
Authors
Scott V. Adams
Polly A. Newcomb
Martin M. Shafer
Charlotte Atkinson
Erin J. Aiello Bowles
Katherine M. Newton
Johanna W. Lampe
Publication date
01-08-2011
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 3/2011
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-011-1383-8

Other articles of this Issue 3/2011

Breast Cancer Research and Treatment 3/2011 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine