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Energy balance and cancer: the role of sex hormones

Published online by Cambridge University Press:  28 February 2007

Timothy J. Key ,
Naomi E. Allen ,
Pia K. Verkasalo  and
Emily Banks
Timothy J. Key*
Affiliation:
Imperial Cancer Research Fund, Cancer Epidemiology Unit, University of Oxford, Oxford OX2 6HE, UK
Naomi E. Allen
Affiliation:
Imperial Cancer Research Fund, Cancer Epidemiology Unit, University of Oxford, Oxford OX2 6HE, UK
Pia K. Verkasalo
Affiliation:
Imperial Cancer Research Fund, Cancer Epidemiology Unit, University of Oxford, Oxford OX2 6HE, UK
Emily Banks
Affiliation:
Imperial Cancer Research Fund, Cancer Epidemiology Unit, University of Oxford, Oxford OX2 6HE, UK
*
*Corresponding author: Dr Timothy J. Key, fax +44 1865 310 545, email [email protected]
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Abstract

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Energy balance can affect the risk for hormone-related cancers by altering sex hormone levels. Energy intake and expenditure are difficult to measure in epidemiological studies, but a chronic excess of intake relative to expenditure leads to a high BMI, which can be accurately measured. In premenopausal women obesity has little effect on the serum concentration of oestradiol, but causes an increase in the frequency of anovular menstrual cycles and thus a reduction in progesterone levels; these changes lead to a large increase in the risk for endometrial cancer, but little change, or a small decrease, in the risk for breast cancer. In post-menopausal women oestradiol levels are not regulated by negative feedback, and obesity causes an increase in the serum concentration of bioavailable oestradiol; this factor causes increases in the risk for both endometrial cancer and breast cancer. The development of ovarian cancer appears to be related more strongly to the frequency of ovulation than to direct effects of circulating levels of sex hormones, and BMI is not clearly associated with the risk for ovarian cancer. In men, increasing BMI has little effect on bioavailable androgen levels, and any effect of obesity on prostate cancer risk is small.

Keywords

Energy balanceObesityCancerSex hormones
Type
Macronutrient Metabolism Group Symposium on ‘Energy flux and cancer’
Information
Proceedings of the Nutrition Society , Volume 60 , Issue 1 , February 2001 , pp. 81 - 89
Copyright
Copyright © The Nutrition Society 2001

References

Adami, H-O, Hsieh, CC, Lambe, M, Trichopoulos, D, Leon, D, Persson, I, Ekbom, A & Janson, PO (1994) Parity, age at first childbirth, and risk of ovarian cancer. Lancet 344, 1250–1254.CrossRefGoogle ScholarPubMed
Albanes, D (1990) Energy balance, body size, and cancer. Critical Reviews in Oncology-Hematology 10, 283–303.CrossRefGoogle ScholarPubMed
Albanes, D (1998) Height, early energy intake, and cancer: evidence mounts for the relation of energy intake to adult malignancies. British Medical Journal 317, 1331–1332.CrossRefGoogle ScholarPubMed
Albanes, D & Winick, M (1988) Are cell number and cell proliferation risk factors for cancer? Journal of the National Cancer Institute 80, 772–774.CrossRefGoogle ScholarPubMed
Allen, NE, Appleby, PN, Davey, GK & Key, TJ (2000) Hormones and diet: low insulin-like growth factor-1 but normal bioavailable androgens in vegan men. British Journal of Cancer 83, 95–97.CrossRefGoogle ScholarPubMed
Anderson, TJ, Ferguson, DJP & Raab, GM (1982) Cell turnover in the 'resting' human breast: influence of parity, contraceptive pill, age and laterality. British Journal of Cancer 46, 376–382.CrossRefGoogle ScholarPubMed
Andersson, S-O, Wolk, A, Bergström, R, Adami, H-O, Engholm, G, Englund, A & Nyrén, O (1997) Body size and prostate cancer: a 20-year follow-up study among 135006 Swedish construction workers. Journal of the National Cancer Institute 89, 385–389.CrossRefGoogle ScholarPubMed
Banks, E, Beral, V & Reeves, G (1997) The epidemiology of epithelial ovarian cancer: a review. International Journal of Gynaelogical Cancer 7, 425–438.CrossRefGoogle Scholar
Beresford, SAA, Weiss, NS, Voigt, LF & McKnight, B (1997) Risk of endometrial cancer in relation to use of oestrogen combined with cyclic progestagen therapy in postmenopausal women. Lancet 349, 458–461.CrossRefGoogle ScholarPubMed
Booth, M, Beral, V & Smith, P (1989) Risk factors for ovarian cancer: a case control study. British Journal of Cancer 60, 592–598.CrossRefGoogle ScholarPubMed
Casagrande, JT, Louie, EW, Pike, MC, Roy, S, Ross, RK & Henderson, BE (1979) 'Incessant Ovulation' and ovarian cancer. Lancet ii, 170–172.CrossRefGoogle Scholar
Coffey, DS & Isaacs, JT (1981) Control of prostate growth. Urology 13, Suppl., 17s–24s.Google Scholar
Cohen, SM & Ellwein, LB (1990) Cell proliferation in carcinogenesis. Science 249, 1007–1011.CrossRefGoogle ScholarPubMed
Collaborative Group on Hormonal Factors in Breast Cancer (1997) Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52705 women with breast cancer and 108411 women without breast cancer. Lancet 350, 1047–1059.CrossRefGoogle Scholar
Dunn, JF, Nisula, BC & Rodbard, D (1981) Transport of steroid hormones: binding of 21 endogenous steroids to both testosterone-binding globulin and corticosteroid-binding globulin in human plasma. Journal of Clinical Endocrinology and Metabolism 53, 58–68.CrossRefGoogle ScholarPubMed
Eaton, NE, Reeves, GK, Appleby, PN & Key, TJ (1999) Endogenous sex hormones and prostate cancer: a quantitative review of prospective studies. British Journal of Cancer 80, 930–934.CrossRefGoogle ScholarPubMed
Farrow, DC, Weiss, NS, Lyon, JL & Daling, JR (1989) Association of obesity and ovarian cancer in a case-control study. American Journal of Epidemiology 129, 1300–1304.CrossRefGoogle ScholarPubMed
Fathalla, MF (1971) Incessant ovulation – a factor in ovarian neoplasia? Lancet ii, 163.CrossRefGoogle Scholar
Field, AE, Colditz, GA, Willett, WC, Longcope, C & McKinlay, JB (1994) The relation of smoking, age, relative weight and dietary intake to serum adrenal steroids, sex hormones and sex hormone-binding globulin in middle-aged men. Journal of Clinical Endocrinology and Metabolism 79, 1310–1316.Google ScholarPubMed
Folsom, AR, Kaye, SA, Potter, JD & Prineas, RJ (1989) Association of incident carcinoma of the endometrium with body weight and fat distribution in older women: early findings of the Iowa Women's Health Study. Cancer Research 49, 6828–6831.Google ScholarPubMed
Franceschi, S, La Vecchia, C, Booth, M, Tzonou, A, Negri, E, Parazzini, F, Trichopoulos, D & Beral, V (1991) Pooled analysis of 3 European case-control studies of ovarian cancer: II Age at menarche and at menopause. International Journal of Cancer 49, 57–60.CrossRefGoogle ScholarPubMed
Franceschi, S, La Vecchia, C, Helmrich, SP, Mangioni, C & Tognoni, G (1982) Risk factors for epithelial ovarian cancer in Italy. American Journal of Epidemiology 115, 714–719.CrossRefGoogle ScholarPubMed
Frankel, S, Gunnell, DJ, Peters, TJ, Maynard, M & Davey Smith, G (1998) Childhood energy intake and adult mortality from cancer: the Boyd Orr cohort study. British Medical Journal 316, 499–504.CrossRefGoogle ScholarPubMed
Franks, S, Kiddy, DS, Hamilton-Fairley, D, Bush, A, Sharp, PS & Reed, MJ (1991) The role of nutrition and insulin in the regulation of sex hormone binding globulin. Journal of Steroid Biochemistry and Molecular Biology 39, 835–838.CrossRefGoogle ScholarPubMed
Freedman, LS, Clifford, C & Messina, M (1990) Analysis of dietary fat, calories, body weight, and the development of mammary tumors in rats and mice: a review. Cancer Research 50, 5710–5719.Google ScholarPubMed
Galanis, DJ, Kolonel, LN, Lee, J & Le Marchand, L (1998) Anthropometric predictors of breast cancer incidence and survival in a multi-ethnic cohort of female residents of Hawaii, United States. Cancer Causes and Control 9, 217–224.CrossRefGoogle Scholar
Gann, PH, Hennekens, CH, Ma, J, Longcope, C & Stampfer, MJ (1996) Prospective study of sex hormone levels and risk of prostate cancer. Journal of the National Cancer Institute 88, 1118–1126.CrossRefGoogle ScholarPubMed
Gerber, M & Corpet, D (1999) Energy balance and cancers. European Journal of Cancer Prevention 8, 77–89.CrossRefGoogle ScholarPubMed
Giovannucci, E, Rimm, EB, Stampfer, MJ, Colditz, GA & Willett, WC (1997) Height, body weight, and risk of prostate cancer. Cancer Epidemiology, Biomarkers and Prevention 6, 557–563.Google ScholarPubMed
Grenman, S, Rönnemaa, T, Irjala, K, Kaihola, HL & Grönroos, M (1986) Sex steroid, gonadotropin, cortisol, and prolactin levels in healthy, massively obese women: correlation with abdominal fat cell size and effect of weight reduction. Journal of Clinical Endocrinology and Metabolism 63, 1257–1261.CrossRefGoogle ScholarPubMed
Gunnell, DJ, Davey Smith, G, Holly, JMP & Frankel, S (1998) Leg length and risk of cancer in the Boyd Orr cohort. British Medical Journal 317, 1350–1351.CrossRefGoogle ScholarPubMed
Hartge, P, Schiffman, MH, Hoover, R, McGowan, L, Lesher, L & Norris, HJ (1989) A case-control study of epithelial ovarian cancer. American Journal of Obstetrics and Gynaecology 161, 10–16.CrossRefGoogle ScholarPubMed
Hebert, JR, Hurley, TG, Olendzki, BC, Teas, J, Ma, Y & Hampl, JS (1998) Nutritional and socio-economic factors in relation to prostate cancer mortality: a cross-national study. Journal of the National Cancer Institute 90, 1637–1647.CrossRefGoogle Scholar
Helzlsouer, KJ, Alberg, AJ, Gordon, GB, Longcope, C, Bush, TL, Hoffman, SC & Comstock, GW (1995) Serum gonadotropins and steroid hormones and the development of ovarian cancer. Journal of the American Medical Association 274, 1926–1930.CrossRefGoogle ScholarPubMed
Henderson, BE, Casagrande, MC, Pike, MC, Mack, T, Rosario, I & Duke, A (1983) The epidemiology of endometrial cancer in young women. British Journal of Cancer 47, 749–756.CrossRefGoogle ScholarPubMed
Herrinton, LJ, Weiss, NS, Beresford, SA, Stanford, JL, Wolfla, DM, Feng, Z & Scott, CR (1995) Lactose and galactose intake and metabolism in relation to the risk of epithelial ovarian cancer. American Journal of Epidemiology 141, 407–416.CrossRefGoogle Scholar
Hildreth, NG, Kelsey, JL, LiVolsi, VA, Fischer, DB, Holford, TR, Mostow, ED, Schwartz, PE & White, C (1981) An epidemiologic study of epithelial carcinoma of the ovary. American Journal of Epidemiology 114, 398–405.CrossRefGoogle ScholarPubMed
Huang, Z, Hankinson, SE, Colditz, GA, Stampfer, MJ, Hunter, DJ, Manson, JE, Hennekens, CH, Rosner, B, Speizer, FE & Willett, WC (1997) Dual effects of weight and weight gain on breast cancer risk. Journal of the American Medical Association 278, 1407–1411.CrossRefGoogle ScholarPubMed
Irwin, KL, Weiss, NS, Lee, NC & Peterson, HB (1991) Tubal sterilisation, hysterectomy, and the subsequent occurrence of epithelial ovarian cancer. American Journal of Epidemiology 134, 362–369.CrossRefGoogle ScholarPubMed
Judd, HL, Shamonki, IM, Frumar, AM & Lagasse, LD (1982) Origin of serum estradiol in postmenopausal women. Obstetrics and Gynecology 59, 680–686.Google ScholarPubMed
Key, TJA & Pike, MC (1988 a) The dose-effect relationship between 'unopposed' oestrogens and endometrial mitotic rate: its central role in explaining and predicting endometrial cancer risk. British Journal of Cancer 57, 205–212.CrossRefGoogle ScholarPubMed
Key, TJA & Pike, MC (1988 b) The role of oestrogens and progestagens in the epidemiology and prevention of breast cancer. European Journal of Cancer and Clinical Oncology 24, 29–43.CrossRefGoogle ScholarPubMed
Key, TJ & Verkasalo, PK (1999) Endogenous hormones and the aetiology of breast cancer (commentary). http://breast cancer-research.com/vol1no1/23aug99/editorial/2 CrossRefGoogle Scholar
Koch, M, Jenkins, H & Gaedke, H (1988) Risk factors of ovarian cancer of epithelial origin: a case-control study. Cancer Detection and Prevention 13, 131–136.Google ScholarPubMed
La Vecchia, C, Franceschi, S, Decarli, A, Gallus, G & Tognoni, G (1984) Risk factors for endometrial cancer at different ages. Journal of the National Cancer Institute 73, 667–671.Google ScholarPubMed
Lew, EA & Garfinkel, L (1979) Variations in mortality by weight among 750,000 men and women. Journal of Chronic Diseases 32, 563–576.CrossRefGoogle Scholar
Liehr, JG (2000) Is estradiol a genotoxic mutagenic carcinogen? Endocrine Reviews 21, 40–54.Google ScholarPubMed
Lund Nilsen, TI & Vatten, LJ (1999) Anthropometry and prostate cancer risk: a prospective study of 22,248 Norwegian men. Cancer Causes and Control 10, 269–275.CrossRefGoogle Scholar
McCay, CM, Crowell, MF & Maynard, LA (1935) The effect of retarded growth upon the length of life span and upon the ultimate body size. Journal of Nutrition 10, 63–79.CrossRefGoogle Scholar
Meyer, F, Moisan, J, Marcoux, D & Bouchard, C (1990) Dietary and physical determinants of menarche. Epidemiology 1, 377–381.CrossRefGoogle ScholarPubMed
Micozzi, MS (1985) Nutrition, body size, and breast cancer. Yearbook of Physical Anthropology 28, 175–206.CrossRefGoogle Scholar
Mink, PJ, Folsom, AR, Sellers, TA & Kushi, LH (1995) Physical activity, waist-to-hip ratio, and other risk factors for ovarian cancer: a follow-up study of older women. Epidemiology 7, 38–45.CrossRefGoogle Scholar
Noble, RL (1977) The development of prostate adenocarcinoma in Nb rats following prolonged sex hormone administration. Cancer Research 37, 1929–1933.Google ScholarPubMed
Nomura, AMY & Kolonel, LN (1991) Prostate cancer: a current perspective. American Journal of Epidemiology 13, 200–227.Google ScholarPubMed
Pariza, MW (1987) Fat, calories, and mammary carcinogenesis: net energy effects. American Journal of Clinical Nutrition 45, 261–263.CrossRefGoogle ScholarPubMed
Pasquali, R, Casimirri, F, De Iasio, R, Mesini, P, Boschi, S, Chierici, B, Flamia, R, Biscotti, M & Vicennati, V (1995) Insulin regulates testosterone and sex hormone-binding globulin concentrations in adult normal-weight and obese men. Journal of Clinical Endocrinology and Metabolism 80, 654–658.Google ScholarPubMed
Pathak, DR & Whittemore, AS (1992) Combined effects of body size, parity, and menstrual events on breast cancer incidence in seven countries. American Journal of Epidemiology 135, 153–168.CrossRefGoogle ScholarPubMed
Petridou, E, Syrigou, E, Toupadaki, N, Zavitsanos, X, Willett, W & Trichopoulos, D (1996) Determinants of age at menarche as early life predictors of breast cancer risk. International Journal of Cancer 68, 193–198.3.0.CO;2-T>CrossRefGoogle ScholarPubMed
Pike, MC, Peters, RK, Cozen, W, Probst-Hensch, NM, Felix, JC, Wan, PC & Mack, TM (1997) Estrogen-progestin replacement therapy and endometrial cancer. Journal of the National Cancer Institute 89, 1110–1116.CrossRefGoogle ScholarPubMed
Pike, MC, Spicer, DV, Dahmoush, L & Press, MF (1993) Estrogens, progestogens, normal breast cell proliferation, and breast cancer risk. Epidemiologic Reviews 15, 17–35.CrossRefGoogle ScholarPubMed
Polychronopoulou, A, Tzonou, A, Hseih, CC, Kaprinis, G, Rebelaskos, A, Toupadaki, N & Trichopoulos, D (1993) Reproductive variables, tobacco, ethanol, coffee and somatometry as risk factors for ovarian cancer. International Journal of Cancer 55, 402–407.CrossRefGoogle ScholarPubMed
Potischman, N, Hoover, RN, Brinton, LA, Siiteri, P, Dorgan, JF, Swanson, CA, Berman, ML, Mortel, R, Twiggs, LB, Barrett, RJ, Wilbanks, GD, Persky, V & Lurain, JR (1996) Case-control study of endogenous steroid hormones and endometrial cancer. Journal of the National Cancer Institute 88, 1127–1135.CrossRefGoogle ScholarPubMed
Preston-Martin, S, Pike, MC, Ross, RK, Jones, PA & Henderson, BE (1990) Increased cell division as a cause of human cancer. Cancer Research 50, 7415–7421.Google ScholarPubMed
Purdie, D, Green, A, Bain, C, Siskind, V, Ward, B, Hacker, N, Quinn, M, Wright, G, Russell, P & Susil, B (1995) Reproductive and other factors and risk of epithelial ovarian cancer: an Australian case-control study. International Journal of Cancer 62, 678–684.CrossRefGoogle ScholarPubMed
Risch, HA (1998) Hormonal etiology of epithelial ovarian cancer, with a hypothesis concerning the role of androgens and progesterone. Journal of the National Cancer Institute 90, 1774–1786.CrossRefGoogle Scholar
Rodriguez, C, Calle, EE, Coates, RJ, Miracle McMahill, HL, Thun, MJ & Heath, CW Jr (1995) Estrogen replacement therapy and fatal ovarian cancer. American Journal of Epidemiology 141, 828–835.CrossRefGoogle ScholarPubMed
Severson, RK, Grove, JS, Nomura, AMY & Stemmermann, GN (1988) Body mass and prostatic cancer: a prospective study. British Medical Journal 297, 713–715.CrossRefGoogle ScholarPubMed
Sherman, BM & Korenman, SG (1974) Measurement of serum LH, FSH, estradiol and progesterone in disorders of the human menstrual cycle: the inadequate luteal phase. Journal of Clinical Endocrinology and Metabolism 39, 145–149.CrossRefGoogle ScholarPubMed
Shu, XO, Brinton, LA, Gao, YT & Yuan, JM (1989) Population-based case-control study of ovarian cancer in Shanghai. Cancer Research 49, 3670–3674.Google ScholarPubMed
Siiteri, PK & MacDonald, PC (1973) Role of extraglandular estrogen in human endocrinology. In Handbook of Physiology, pp. 615–629 [Geiger, SR, Astwood, EB and Greep, RO, editors] Washington, DC: American Physiological Society.Google Scholar
Slattery, ML, Schuman, KL, West, DW, French, TK & Robison, LM (1989) Nutrient intake and ovarian cancer. American Journal of Epidemiology 130, 497–502.CrossRefGoogle ScholarPubMed
Tannenbaum, A (1940) The initiation and growth of tumors. American Journal of Cancer 38, 335–350.Google Scholar
Thomas, HV, Davey, GK & Key, TJ (1999) Oestradiol and sex hormone-binding globulin in premenopausal and post-menopausal meat-eaters, vegetarians and vegans. British Journal of Cancer 80, 1470–1475.CrossRefGoogle ScholarPubMed
Thorling, EB (1996) Obesity, fat intake, energy balance, exercise and cancer risk: a review. Nutrition Research 16, 315–368.CrossRefGoogle Scholar
Trentham-Dietz, A, Newcomb, PA, Storer, BE, Longnecker, MP, Baron, J, Greenberg, ER & Willett, WC (1997) Body size and risk of breast cancer. American Journal of Epidemiology 145, 1011–1019.CrossRefGoogle ScholarPubMed
Tretli, S (1989) Height and weight in relation to breast cancer morbidity and mortality. A prospective study of 570,000 women in Norway. International Journal of Cancer 44, 23–30.CrossRefGoogle Scholar
Ursin, G, Longnecker, MP, Haile, RW & Greenland, S (1995) A meta-analysis of body mass index and risk of premenopausal breast cancer. Epidemiology 6, 137–141.CrossRefGoogle ScholarPubMed
Verkasalo, PK, Thomas, HV, Appleby, PN, Davey, GK & Key, TJ (2001) Circulating levels of sex hormones and their relation to risk factors for breast cancer: a cross-sectional study in 1092 pre- and postmenopausal women. Cancer Causes and Control (In the Press).CrossRefGoogle ScholarPubMed
Vermeulen, A, Kaufman, JM, Deslypere, JP & Thomas, G (1993) Attenuated luteinising hormone (LH) pulse amplitude but normal LH pulse frequency, and its relation to plasma androgens in hypogonadism of obese men. Journal of Clinical Endocrinology and Metabolism 76, 1140–1146.Google ScholarPubMed
Vermeulen, A, Kaufman, JM & Giagulli, VA (1996) Influence of some biological indexes on sex hormone-binding globulin and androgen levels in aging or obese males. Journal of Clinical Endocrinology and Metabolism 81, 1821–1826.Google ScholarPubMed
Weiderpass, E, Adami, H-O, Baron, JA, Magnusson, C, Bergström, R, Lindgren, A, Correia, N & Persson, I (1999) Risk of endometrial cancer following estrogen replacement with and without progestins. Journal of the National Cancer Institute 91, 1131–1137.CrossRefGoogle ScholarPubMed
Weiderpass, E, Persson, I, Adami, H-O, Magnusson, C, Lindgren, A & Baron, JA (2000) Body size in different periods of life, diabetes mellitus, hypertension, and risk of postmenopausal endometrial cancer (Sweden). Cancer Causes and Control 11, 185–192.CrossRefGoogle ScholarPubMed
Whittemore, AS, Harris, R, Itnyre, J & the Collaborative Ovarian Cancer Group (1992) Characteristics relating to ovarian cancer risk: collaborative analysis of 12 US case-control studies. II. Invasive epithelial ovarian cancers in white women. American Journal of Epidemiology 136, 1184–1203.CrossRefGoogle ScholarPubMed
Wu, AH, Whittemore, AS, Kolonel, LN, John, EM, Gallagher, RP, West, DW, Hankin, J, The, CZ, Dreon, DM & Paffenbarger, RS Jr (1995) Serum androgens and sex hormone-binding globulin in relation to lifestyle factors in older African-American, white and Asian men in the United States and Canada. Cancer Epidemiology, Biomarkers and Prevention 4, 735–741.Google ScholarPubMed
Wu, ML, Whittemore, AS, Paffenbarger, RS Jr, Sarles, DL, Kampert, JB, Grosser, S, Jung, DL, Ballon, S, Hendrickson, M & Mohle Boetani, J (1988) Personal and environmental characteristics related to epithelial ovarian cancer. I. Reproductive and menstrual events and oral contraceptive use. American Journal of Epidemiology 128, 1216–1227.CrossRefGoogle ScholarPubMed
Zhang, Y-W, Stern, B & Rebar, RW (1984) Endocrine comparison of obese menstruating and amenorrheic women. Journal of Clinical Endocrinology and Metabolism 58, 1077–1083.CrossRefGoogle ScholarPubMed