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Urological Oncology: Testis Cancer
2734
TESTIS CANCER
Urological Oncology: Testis Cancer Endogenous Steroid Hormone Levels in Early Pregnancy and Risk of Testicular Cancer in the Offspring: A Nested Case-Referent Study K. Holl, E. Lundin, H. M. Surcel, K. Grankvist, P. Koskela, J. Dillner, G. Hallmans, G. Wadell, G. H. Olafsdottir, H. M. Ogmundsdottir, E. Pukkala, M. Lehtinen, P. Stattin and A. Lukanova Department of Child and Adolescent Health, National Institute for Health and Welfare, Oulu, Finland Int J Cancer 2009; 124: 2923–2928.
According to the leading hypothesis on testicular cancer (TC) etiology exposure to a specific pattern of steroid hormones in utero, in particular, to high levels of estrogens and low levels of androgens is the major determinant of TC risk in the offspring. We performed a case-referent study nested within Finnish, Swedish and Icelandic maternity cohorts exploiting early pregnancy serum samples to evaluate the role of maternal endogenous steroid hormones with regard to the risk of TC. TC cases and referents were aged between 0 and 25 years. For each case-index mother pair, three or four matched referent-referent mother pairs were identified using national population registries. First trimester or early second trimester sera were retrieved from the index mothers of 73 TC cases and 286 matched referent mothers, and were tested for dehydroepiandrosterone sulfate (DHEAS), androstenedione, testosterone, estradiol, estrone, and sex hormone binding globulin (SHBG). Offspring of mothers with high DHEAS levels had a significantly decreased risk of TC (OR for highest vs. lowest DHEAS quartile, 0.18 (95% CI 0.06 – 0.58). In contrast, offspring of mothers with high androstenedione levels had an increased risk of TC (OR 4.1; 95% CI 1.2–12.0). High maternal total estradiol level also tended to be associated with an increased risk of TC in the offspring (OR 32; 95% CI 0.98 –1,090). We report the first direct evidence that interplay of maternal steroid hormones in the early pregnancy is important in the etiology of TC in the offspring. Editorial Comment: Testicular cancer, although relatively rare, has more than doubled in incidence in the last 40 years. The incidence in Denmark and Norway is substantially higher than in Asian and African populations, at approximately 9/100,000 males compared to 1/100,000 males. Onset at a relatively early age suggests that risk factors may be operative early in life or in utero. The hypothesis is that exposure during fetal life disturbs normal development of the primordial germ cells. Exposure to a specific pattern of steroid hormones in utero may be a major determinant of testicular cancer risk. High levels of estrogen and low levels of androgen are believed to be etiologically important. The authors performed a case reference study nested within Finnish, Swedish and Icelandic cohorts of pregnant women using sera collected early in pregnancy. Blood samples were drawn during the first trimester or the early weeks of the second trimester. Using a pair matched case reference study, 3 or 4 matched mother pairs were identified for each case of testicular cancer. Offspring of mothers with the highest DHEA had a significantly decreased risk of testicular cancer (relative risk 0.17). Offspring of mothers with the highest androstenedione levels had an increased risk of testicular cancer with a crude relative risk of 3.8. This important study provides the first direct evidence of the interplay between maternal steroid hormones during early pregnancy and development of testicular cancer in offspring. Jerome P. Richie, M.D.
TESTIS CANCER
Urological Oncology: Testis Cancer Endogenous Steroid Hormone Levels in Early Pregnancy and Risk of Testicular Cancer in the Offspring: A Nested Case-Referent Study K. Holl, E. Lundin, H. M. Surcel, K. Grankvist, P. Koskela, J. Dillner, G. Hallmans, G. Wadell, G. H. Olafsdottir, H. M. Ogmundsdottir, E. Pukkala, M. Lehtinen, P. Stattin and A. Lukanova Department of Child and Adolescent Health, National Institute for Health and Welfare, Oulu, Finland Int J Cancer 2009; 124: 2923–2928.
According to the leading hypothesis on testicular cancer (TC) etiology exposure to a specific pattern of steroid hormones in utero, in particular, to high levels of estrogens and low levels of androgens is the major determinant of TC risk in the offspring. We performed a case-referent study nested within Finnish, Swedish and Icelandic maternity cohorts exploiting early pregnancy serum samples to evaluate the role of maternal endogenous steroid hormones with regard to the risk of TC. TC cases and referents were aged between 0 and 25 years. For each case-index mother pair, three or four matched referent-referent mother pairs were identified using national population registries. First trimester or early second trimester sera were retrieved from the index mothers of 73 TC cases and 286 matched referent mothers, and were tested for dehydroepiandrosterone sulfate (DHEAS), androstenedione, testosterone, estradiol, estrone, and sex hormone binding globulin (SHBG). Offspring of mothers with high DHEAS levels had a significantly decreased risk of TC (OR for highest vs. lowest DHEAS quartile, 0.18 (95% CI 0.06 – 0.58). In contrast, offspring of mothers with high androstenedione levels had an increased risk of TC (OR 4.1; 95% CI 1.2–12.0). High maternal total estradiol level also tended to be associated with an increased risk of TC in the offspring (OR 32; 95% CI 0.98 –1,090). We report the first direct evidence that interplay of maternal steroid hormones in the early pregnancy is important in the etiology of TC in the offspring. Editorial Comment: Testicular cancer, although relatively rare, has more than doubled in incidence in the last 40 years. The incidence in Denmark and Norway is substantially higher than in Asian and African populations, at approximately 9/100,000 males compared to 1/100,000 males. Onset at a relatively early age suggests that risk factors may be operative early in life or in utero. The hypothesis is that exposure during fetal life disturbs normal development of the primordial germ cells. Exposure to a specific pattern of steroid hormones in utero may be a major determinant of testicular cancer risk. High levels of estrogen and low levels of androgen are believed to be etiologically important. The authors performed a case reference study nested within Finnish, Swedish and Icelandic cohorts of pregnant women using sera collected early in pregnancy. Blood samples were drawn during the first trimester or the early weeks of the second trimester. Using a pair matched case reference study, 3 or 4 matched mother pairs were identified for each case of testicular cancer. Offspring of mothers with the highest DHEA had a significantly decreased risk of testicular cancer (relative risk 0.17). Offspring of mothers with the highest androstenedione levels had an increased risk of testicular cancer with a crude relative risk of 3.8. This important study provides the first direct evidence of the interplay between maternal steroid hormones during early pregnancy and development of testicular cancer in offspring. Jerome P. Richie, M.D.