It has been suggested that cancers of the testis and breast are associated with exposure to estrogens and other hormones in utero. Twin pregnancies have higher levels of pregnancy-associated hormones than singleton pregnancies, and these levels may be higher in dizygotic than in monozygotic twin pregnancies. Through a large population-based study of twins, we assessed the hypothesis that levels of pregnancy-associated hormones have etiologic importance for cancers of the testis, breast, and other sites. The incidence of all cancers among 46,767 members of the Swedish Twin Registry was compared with the incidence among the Swedish general population. We found testicular cancer excess among dizygotic twins (observed/expected [O/E] ratio=1.6, 95 percent confidence interval [CI]=1.0–2.6) that was greater for men younger than 35 years (O/E ratio=2.3, CI=1.1–4.2) compared with older men (O/E ratio = 1.2, CI=0.5–2.4). In addition, a substantially elevated incidence of breast cancer was observed in dizygotic twin women aged 20 to 29 years (O/E=6.7, CI=2.9–13.1). None of the other age or zygosity groups showed notable elevations in incidence of testicular, breast, or other cancers. We conclude that dizygotic twinship may be associated with cancer of the breast and testis among young adults. These findings support the concept that pregnancy hormones are associated with risk of testicular and breast cancer, although non-hormonal aspects of twin pregnancy that vary with respect to zygosity cannot be excluded as explanatory factors.
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References
Forman D, Gallagher R, Moller H, Swerdlow TJ. Aetiology and epidemiology of testicular cancer: report of consensus group. Prog Clin Biol Res 1990; 357: 245–53.
Prener A, Hsieh C-c, Engholm G, Trichopoulos D, Jensen OM. Birth order and risk of testicular cancer. Cancer Causes and Control 1992; 3: 265–72.
Swerdlow AJ, Huttly SRA, Smith PG. Prenatal and familial associations of testicular cancer. Br J Cancer 1987; 55: 571–7.
Gershman ST, Stolley PD. A case-control study of testicular cancer using Connecticut tumor registry data. Int J Epidemiol 1988; 17: 738–42.
Brown LM, Pottern LM, Hoover RN. Prenatal and perinatal risk factors for testicular cancer. Cancer Res 1986; 46: 4812–6.
Depue RH, Pike MC, Henderson BE, Estrogen exposure during gestation and risk of testicular cancer. JNCI 1983; 71: 1151–5.
Henderson BE, Benton B, Jing J, Yu MC. Pike MC. Risk factors for cancer of the testis in young men. Int J Cancer 1979; 23: 598–602.
Bernstein L, Pike MC, Depue RH, Ross RK, Moore JW, Henderson BE. Maternal hormone levels in early gestation of cryptorchid males: a case-control study. Br J Cancer 1988; 58: 379–81.
Henderson BE, Bernstein L, Ross RK, Depue RH, Judd HL. The early in utero oestrogen and testosterone environment of blacks and whites: potential efects on male offspring. Br J Cancer 1988; 57: 216–8.
Panagiotopoulou K, Katsouyanni K, Petridou E, Garas Y, Tzonou A, Trichopoulos D. Maternal age, parity, and pregnancy estrogens. Cancer Causes Control 1990; 1: 119–24.
Trichopoulos D. Does breast cancer originate in utero? Lancet 1990; 335: 939–40.
Ekbom A, Trichopoulos D. Adami HO, Hsieh C-c, Lan S. Evidence of prenatal influences on breast cancer risk. Lancet 1992; 340: 1015–8.
Hsieh C-c, Lan S, Ekbom A, Petridou E, Trichopoulous D. Twin membership and breast cancer risk. Am J Epidemiol 1992; 136: 1321–6.
Gonzalez MC, Reyes H, Arrese M, et al. Intrahepatic cholestasis of pregnancy in twin pregnancies. J Hepatol 1989; 9: 84–90.
Duff GB, Brown JB. Urinary oestriol excretion in twin pregnancies. J. Obstet Gynaecol 1974; 81: 695–700.
Beischer NA, Brown JB. The significance of high urinary estriol excretion during pregnancy. J Obstet Gynaecol Brit Cwlth 1968; 75: 622–8.
TambyRaja RL, Ratnam SS. Plasma steroid changes in twin pregnancies. In: Gedda L, Parisi P, Nance W, eds. Twin Research 3. NY, NY (USA): Alan R. Liss, 1981: 189–95.
Thiery M, Dhont M, Vandekerckhove D. Serum HCG and HPL in twin pregnancies. Acta Obstet Gynecol Scand 1976; 56: 495–7.
Wald N, Cuckle H, Wu T, George L. Maternal serum unconjugated oestriol and human chorionic gonadotrophin levels in twin pregnancies: implications for screening for Down's syndrome. Br J Obstet Gynaecol 1991; 98: 905–8.
Steier JA, Myking OL, Ulstein M. Human chorionic gonadotropin in cord blood and peripheral maternal blood in singleton and twin pregnancies at delivery. Acta Obstet Gynecol Scand 1989; 68: 689–92.
Batra S, Sjoberg NO, Aberg A. Human placental lactogen, estradiol-17β, and progesterone levels in the third trimester and their respective values for detecting twin pregnancy. Am J Obstet Gynecol 1978; 131: 69–72.
Donat J, Jirkalova V. HCG, FSH, a oxytocinaza v prvnim trimestru tehotenstiv s dvojcaty. Cs Gynekol 1979; 44: 266–71.
Kappel B, Hansen K, Moller J, Faaborg-Andersen J. Human placental lactogen and dU-estrogen levels in normal twin pregnancies. Acta Genet Med Gemellol 1985; 34: 59–66.
Cederlof R, Friberg L, Lundman T. The interactions of smoking, environment and heredity and their implications for disease etiology: a report of epidemiological studies on the Swedish Twin Registries. Acta Med Scand Suppl 1977; 612: 1–128.
Cederlof R, Friberg L, Jonsson E, Kaij L. Studies on similarity of diagnosis in twins with the aid of mailed questionnaires. Acta Genet 1961; 11: 338–62.
Harvald B, Hauge M. Hereditary factors elucidated by twins studies. In: Neel JV, Shaw MW, Schull WJ, eds. Genetics and the Epidemiology of Chronic Disease. Bethesda, MD (USA): US Department of Health, Education, and Welfare, 1966; Pub. Health Service Pub. No. 1163.
Nichols RC, Bilbro WC. The diagnosis of twin zygosity. Acta Genet Stat Med (Basel) 1966; 16: 265–75.
World Health Organization. International Classification of Diseases, Seventh Revision. Geneva, Switzerland: WHO, 1957.
Ries LAG, Hankey BF, Miller BA, Hartman AM, Edwards BK. Cancer Statistics Review 1973–88. Bethesda, MD (USA): National Cancer Institute, 1991; NIH Pub. No. 91–2789.
Braun MM, Caporaso NE, Briton LA, Page WF. Re: “Twin membership and breast cancer risk,”. Am J Epidemiol 1994; 140: 575–6.
Li FP, Fraumeni JF. Testicular cancers in children: epidemiologic characteristics. JNCI 1972; 48: 1575–82.
Holm NV. Studies of cancer in the Danish twin population.I. Breast cancer. In: Gedda L, Parisi P, Nance W, eds. Twin Research 3. NY, NY (USA): Alan R. Liss, 1988(69C): 211–6.
Cederlof R, Floderus-Myrhed B. Cancer mortality and morbidity among 23,000 unselected twin pairs. In: Genetic and Environmental Factors in Experimental and Human Cancer. II. Gelboin V et al, eds. Tokyo, Japan: Japan Sci. Soc. Press, 1980.
Kaprio J, Teppo L, Koskenvuo M, Pukkala E. Cancer in adult same-sexed twins: a historical cohort study. In: Gedda L, Parisi P, Nance WE, eds. Twin Research 3: Epidemiological and Clinical Studies. New York, NY (USA): Alan R. Liss, 1981.
Ramos-Arroyo MA, Ulbright TM, Yu PL, Christian JC. Twin study: relationship between birth weight, zygosity, placentation, and pathologic placental changes. Acta Genet Med Gemellol 1988; 37: 229–38.
Shipley PW, Wray JA, Hechter HH, Arellano MG, Borhani NO. Frequency of twinning in California. Am J Epidemiol 1967; 85: 147–56.
Martin NG, El Beaini JL, Olsen ME, Bhatnagar AS, Macourt D. Gonadotropin levels in mothers who have had two sets of DZ twins. Acta Genet Med Gemellol 1984; 33: 131–9.
Nylander PPS. The factors that influence twinning rates. Acta Genet Med Gemellol 1981; 30: 189–202.
Nylander PPS. Pituitary gonadotropins and multiple births in Nigeria. Acta Genet Med Gemellol 1973; 22(Suppl): 198–201.
Phillips DIW. Twin studies in medical research: can they tell us whether diseases are genetically determined? Lancet 1993; 341: 1008–9.
Walker AH, Ross RK, Haile RWC, Henderson BE. Hormonal factors and risk of ovarian germ cell cancer in young women. Br J Cancer 1988; 57: 418–22.
dos Santos Silva I, Swerdlow AJ. Ovarian germ cell malignancies in England: epidemiologic parallels with testicular cancer. Br J Cancer 1991; 63: 814–8.
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The Swedish Twin Registry is supported by funds from the John D. and Catherine T. MacArthur Foundation.
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Braun, M.M., Ahlbom, A., Floderus, B. et al. Effect of twinship on incidence of cancer of the testis, breast, and other sites (Sweden). Cancer Causes Control 6, 519–524 (1995). https://doi.org/10.1007/BF00054160
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DOI: https://doi.org/10.1007/BF00054160