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2. Central adiposity, obesity during early adulthood, and pancreatic cancer mortality in a pooled analysis of cohort studies

Author

Genkinger, J. M., Kitahara, C. M., Bernstein, L., Berrington de Gonzalez, A., Brotzman, M., Elena, J. W., Giles, G. G., Hartge, P., Singh, P. N., Stolzenberg-Solomon, R. Z., Weiderpass, E., Adami, H.-O., Anderson, K. E., Beane-Freeman, L. E., Buring, J. E., Fraser, G. E., Fuchs, C. S., Gapstur, S. M., Gaziano, J. M., Helzlsouer, K. J., Lacey, J. V., Jr, Linet, M. S., Liu, J. J., Park, Y., Peters, U., Purdue, M. P., Robien, K., Schairer, C., Sesso, H. D., Visvanathan, K., White, E., Wolk, A., Wolpin, B. M., Zeleniuch-Jacquotte, A., and Jacobs, E. J.

Published
2015
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7. A Meta-analysis of Individual Participant Data Reveals an Association between Circulating Levels of IGF-I and Prostate Cancer Risk

Author

Travis, RC, Appleby, P N, Martin, RM, Holly, JMP, Albanes, D, Black, A, Bueno-de-Mesquita, HB, Chan, JM, Chen, C (Christopher Li Hsian), Chirlaque, MD, Cook, M B, Deschasaux, M, Donovan, JL, Ferrucci, L, Galan, P, Giles, GG, Giovannucci, E L, Gunter, MJ, Habel, L A, Hamdy, FC, Helzlsouer, K J, Hercberg, S, Hoover, RN, Janssen, J.A.M.J.L., Kaaks, R, Kubo, T, Le Marchand, L, Metter, EJ, Mikami, K, Morris, J K, Neal, DE, Neuhouser, ML, Ozasa, K, Palli, D, Platz, EA, Pollak, MN, Price, AJ, Roobol - Bouts, Monique, Schaefer, C, Schenk, J M, Severi, G, Stampfer, MJ, Stattin, P, Tamakoshi, A, Tangen, C M, Touvier, M, Wald, N J, Weiss, NS, Ziegler, RG, Key, TJ, Allen, NE, Endogenous Hormones, Nutr, Internal Medicine, and Urology

Subjects
SDG 3 - Good Health and Well-being
Published
2016

8. Circulating sex hormones and breast cancer risk factors in postmenopausal women: reanalysis of 13 studies

Author

Key, T. J. Appleby, P. N. Reeves, G. K. Roddam, A. W. and Helzlsouer, K. J. Alberg, A. J. Rollison, D. E. Dorgan, J. F. Brinton, L. A. Overvad, K. Kaaks, R. Trichopoulou, A. and Clavel-Chapelon, F. Panico, S. Duell, E. J. Peeters, P. H. M. Rinaldi, S. Riboli, E. Fentiman, I. S. Dowsett, M. and Manjer, J. Lenner, P. Hallmans, G. Baglietto, L. and English, D. R. Giles, G. G. Hopper, J. L. Severi, G. and Morris, H. A. Koenig, K. Zeleniuch-Jacquotte, A. Arslan, A. A. Toniolo, P. Shore, R. E. Krogh, V. Micheli, A. and Berrino, F. Muti, P. Barrett-Connor, E. Laughlin, G. A. and Kabuto, M. Akiba, S. Stevens, R. G. Neriishi, K. Land, C. E. Cauley, J. A. Lui, Li Yung Cummings, Steven R. and Gunter, M. J. Rohan, T. E. Strickler, H. D. Endogenous Hormones Breast Canc

Abstract

BACKGROUND: Breast cancer risk for postmenopausal women is positively associated with circulating concentrations of oestrogens and androgens, but the determinants of these hormones are not well understood. METHODS: Cross-sectional analyses of breast cancer risk factors and circulating hormone concentrations in more than 6000 postmenopausal women controls in 13 prospective studies. RESULTS: Concentrations of all hormones were lower in older than younger women, with the largest difference for dehydroepiandrosterone sulphate (DHEAS), whereas sex hormone-binding globulin (SHBG) was higher in the older women. Androgens were lower in women with bilateral ovariectomy than in naturally postmenopausal women, with the largest difference for free testosterone. All hormones were higher in obese than lean women, with the largest difference for free oestradiol, whereas SHBG was lower in obese women. Smokers of 15+ cigarettes per day had higher levels of all hormones than non-smokers, with the largest difference for testosterone. Drinkers of 20+ g alcohol per day had higher levels of all hormones, but lower SHBG, than non-drinkers, with the largest difference for DHEAS. Hormone concentrations were not strongly related to age at menarche, parity, age at first full-term pregnancy or family history of breast cancer. CONCLUSION: Sex hormone concentrations were strongly associated with several established or suspected risk factors for breast cancer, and may mediate the effects of these factors on breast cancer risk. British Journal of Cancer (2011) 105, 709-722. doi:10.1038/bjc.2011.254 www.bjcancer.com Published online 19 July 2011 (C) 2011 Cancer Research UK

Published
2011

9. Steroid hormone measurements from different types of assays in relation to body mass index and breast cancer risk in postmenopausal women: Reanalysis of eighteen prospective studies

Author

Key, T. J., Appleby, P. N., Reeves, G. K., Travis, R. C., Brinton, L. A., Dallal, C. M., Helzlsouer, K. J., Hoffman-Bolton, J., Visvanathan, K., Dorgan, J. F., Falk, R. T., Gapstur, S. M., Gaudet, M. M., Kaaks, R., Riboli, E., Rinaldi, S., Key, T., Manjer, Jonas, Hallmans, G., Giles, G. G., Le Marchand, L., Kolonel, L. N., Henderson, B. E., Tworoger, S. S., Hankinson, S. E., Zeleniuch-Jacquotte, A., Koenig, K., Krogh, V., Sieri, S., Muti, P., Ziegler, R. G., Schairer, C., Fuhrman, B. J., Barrett-Connor, E., Laughlin, G. A., Grant, E. J., Cologne, J., Ohishi, W., Hida, A., Cauley, J. A., Fourkala, E.-O., Rohan, T. E., Strickler, H. D., Gunter, M. J., Key, T. J., Appleby, P. N., Reeves, G. K., Travis, R. C., Brinton, L. A., Dallal, C. M., Helzlsouer, K. J., Hoffman-Bolton, J., Visvanathan, K., Dorgan, J. F., Falk, R. T., Gapstur, S. M., Gaudet, M. M., Kaaks, R., Riboli, E., Rinaldi, S., Key, T., Manjer, Jonas, Hallmans, G., Giles, G. G., Le Marchand, L., Kolonel, L. N., Henderson, B. E., Tworoger, S. S., Hankinson, S. E., Zeleniuch-Jacquotte, A., Koenig, K., Krogh, V., Sieri, S., Muti, P., Ziegler, R. G., Schairer, C., Fuhrman, B. J., Barrett-Connor, E., Laughlin, G. A., Grant, E. J., Cologne, J., Ohishi, W., Hida, A., Cauley, J. A., Fourkala, E.-O., Rohan, T. E., Strickler, H. D., and Gunter, M. J.

Abstract

Epidemiological studies have examined breast cancer risk in relation to sex hormone concentrations measured by different methods: "extraction" immunoassays (with prior purification by organic solvent extraction, with or without column chromatography), "direct" immunoassays (no prior extraction or column chromatography), and more recently with mass spectrometry-based assays. We describe the associations of estradiol, estrone and testosterone with both body mass index and breast cancer risk in postmenopausal women according to assay method, using data from a collaborative pooled analysis of 18 prospective studies. In general, hormone concentrations were highest in studies that used direct assays and lowest in studies that used mass spectrometry-based assays. Estradiol and estrone were strongly positively associated with body mass index, regardless of the assay method; testosterone was positively associated with body mass index for direct assays, but less clearly for extraction assays, and there were few data for mass spectrometry assays. The correlations of estradiol with body mass index, estrone and testosterone were lower for direct assays than for extraction and mass spectrometry assays, suggesting that the estimates from the direct assays were less precise. For breast cancer risk, all three hormones were strongly positively associated with risk regardless of assay method (except for testosterone by mass spectrometry where there were few data), with no statistically significant differences in the trends, but differences may emerge as new data accumulate. Future epidemiological and clinical research studies should continue to use the most accurate assays that are feasible within the design characteristics of each study.

Published
2015

10. Circulating sex hormones and breast cancer risk factors in postmenopausal women : reanalysis of 13 studies.

Author

Key, T J, Appleby, P N, Reeves, G K, Roddam, A W, Helzlsouer, K J, Alberg, A J, Rollison, D E, Dorgan, J F, Brinton, L A, Overvad, K, Kaaks, R, Trichopoulou, A, Clavel-Chapelon, F, Panico, S, Duell, E J, Peeters, P H M, Rinaldi, S, Fentiman, I S, Dowsett, M, Manjer, J, Lenner, Per, Hallmans, Göran, Baglietto, L, English, D R, Giles, G G, Hopper, J L, Severi, G, Morris, H A, Hankinson, S E, Tworoger, S S, Koenig, K, Zeleniuch-Jacquotte, A, Arslan, A A, Toniolo, P, Shore, R E, Krogh, V, Micheli, A, Berrino, F, Barrett-Connor, E, Laughlin, G A, Kabuto, M, Akiba, S, Stevens, R G, Neriishi, K, Land, C E, Cauley, J A, Lui, Li Yung, Cummings, Steven R, Gunter, M J, Rohan, T E, Strickler, H D, Key, T J, Appleby, P N, Reeves, G K, Roddam, A W, Helzlsouer, K J, Alberg, A J, Rollison, D E, Dorgan, J F, Brinton, L A, Overvad, K, Kaaks, R, Trichopoulou, A, Clavel-Chapelon, F, Panico, S, Duell, E J, Peeters, P H M, Rinaldi, S, Fentiman, I S, Dowsett, M, Manjer, J, Lenner, Per, Hallmans, Göran, Baglietto, L, English, D R, Giles, G G, Hopper, J L, Severi, G, Morris, H A, Hankinson, S E, Tworoger, S S, Koenig, K, Zeleniuch-Jacquotte, A, Arslan, A A, Toniolo, P, Shore, R E, Krogh, V, Micheli, A, Berrino, F, Barrett-Connor, E, Laughlin, G A, Kabuto, M, Akiba, S, Stevens, R G, Neriishi, K, Land, C E, Cauley, J A, Lui, Li Yung, Cummings, Steven R, Gunter, M J, Rohan, T E, and Strickler, H D

Abstract

BACKGROUND: Breast cancer risk for postmenopausal women is positively associated with circulating concentrations of oestrogens and androgens, but the determinants of these hormones are not well understood. METHODS: Cross-sectional analyses of breast cancer risk factors and circulating hormone concentrations in more than 6000 postmenopausal women controls in 13 prospective studies. RESULTS: Concentrations of all hormones were lower in older than younger women, with the largest difference for dehydroepiandrosterone sulphate (DHEAS), whereas sex hormone-binding globulin (SHBG) was higher in the older women. Androgens were lower in women with bilateral ovariectomy than in naturally postmenopausal women, with the largest difference for free testosterone. All hormones were higher in obese than lean women, with the largest difference for free oestradiol, whereas SHBG was lower in obese women. Smokers of 15+ cigarettes per day had higher levels of all hormones than non-smokers, with the largest difference for testosterone. Drinkers of 20+ g alcohol per day had higher levels of all hormones, but lower SHBG, than non-drinkers, with the largest difference for DHEAS. Hormone concentrations were not strongly related to age at menarche, parity, age at first full-term pregnancy or family history of breast cancer. CONCLUSION: Sex hormone concentrations were strongly associated with several established or suspected risk factors for breast cancer, and may mediate the effects of these factors on breast cancer risk.

Published
2011
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14. Circulating 25-Hydroxyvitamin D and Risk of Epithelial Ovarian Cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers

Author

Zheng, W., primary, Danforth, K. N., additional, Tworoger, S. S., additional, Goodman, M. T., additional, Arslan, A. A., additional, Patel, A. V., additional, McCullough, M. L., additional, Weinstein, S. J., additional, Kolonel, L. N., additional, Purdue, M. P., additional, Shu, X.-O., additional, Snyder, K., additional, Steplowski, E., additional, Visvanathan, K., additional, Yu, K., additional, Zeleniuch-Jacquotte, A., additional, Gao, Y.-T., additional, Hankinson, S. E., additional, Harvey, C., additional, Hayes, R. B., additional, Henderson, B. E., additional, Horst, R. L., additional, and Helzlsouer, K. J., additional

Published
2010
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15. Circulating 25-Hydroxyvitamin D and Risk of Non-Hodgkin Lymphoma: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers

Author

Purdue, M. P., primary, Freedman, D. M., additional, Gapstur, S. M., additional, Helzlsouer, K. J., additional, Laden, F., additional, Lim, U., additional, Maskarinec, G., additional, Rothman, N., additional, Shu, X.-O., additional, Stevens, V. L., additional, Zeleniuch-Jacquotte, A., additional, Albanes, D., additional, Bertrand, K., additional, Weinstein, S. J., additional, Yu, K., additional, Irish, L., additional, Horst, R. L., additional, Hoffman-Bolton, J., additional, Giovannucci, E. L., additional, Kolonel, L. N., additional, Snyder, K., additional, Willett, W., additional, Arslan, A. A., additional, Hayes, R. B., additional, Zheng, W., additional, Xiang, Y.-B., additional, and Hartge, P., additional

Published
2010
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16. Circulating 25-Hydroxyvitamin D and Risk of Kidney Cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers

Author

Gallicchio, L., primary, Moore, L. E., additional, Stevens, V. L., additional, Ahn, J., additional, Albanes, D., additional, Hartmuller, V., additional, Setiawan, V. W., additional, Helzlsouer, K. J., additional, Yang, G., additional, Xiang, Y.-B., additional, Shu, X.-O., additional, Snyder, K., additional, Weinstein, S. J., additional, Yu, K., additional, Zeleniuch-Jacquotte, A., additional, Zheng, W., additional, Cai, Q., additional, Campbell, D. S., additional, Chen, Y., additional, Chow, W.-H., additional, Horst, R. L., additional, Kolonel, L. N., additional, McCullough, M. L., additional, Purdue, M. P., additional, and Koenig, K. L., additional

Published
2010
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17. Circulating 25-Hydroxyvitamin D and Risk of Esophageal and Gastric Cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers

Author

Abnet, C. C., primary, Chen, Y., additional, Chow, W.-H., additional, Gao, Y.-T., additional, Helzlsouer, K. J., additional, Le Marchand, L., additional, McCullough, M. L., additional, Shikany, J. M., additional, Virtamo, J., additional, Weinstein, S. J., additional, Xiang, Y.-B., additional, Yu, K., additional, Zheng, W., additional, Albanes, D., additional, Arslan, A. A., additional, Campbell, D. S., additional, Campbell, P. T., additional, Hayes, R. B., additional, Horst, R. L., additional, Kolonel, L. N., additional, Nomura, A. M. Y., additional, Purdue, M. P., additional, Snyder, K., additional, and Shu, X.-O., additional

Published
2010
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18. Circulating 25-Hydroxyvitamin D and Risk of Pancreatic Cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers

Author

Stolzenberg-Solomon, R. Z., primary, Jacobs, E. J., additional, Arslan, A. A., additional, Qi, D., additional, Patel, A. V., additional, Helzlsouer, K. J., additional, Weinstein, S. J., additional, McCullough, M. L., additional, Purdue, M. P., additional, Shu, X.-O., additional, Snyder, K., additional, Virtamo, J., additional, Wilkins, L. R., additional, Yu, K., additional, Zeleniuch-Jacquotte, A., additional, Zheng, W., additional, Albanes, D., additional, Cai, Q., additional, Harvey, C., additional, Hayes, R., additional, Clipp, S., additional, Horst, R. L., additional, Irish, L., additional, Koenig, K., additional, Le Marchand, L., additional, and Kolonel, L. N., additional

Published
2010
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19. Circulating 25-Hydroxyvitamin D and Risk of Endometrial Cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers

Author

Zeleniuch-Jacquotte, A., primary, Gallicchio, L., additional, Hartmuller, V., additional, Helzlsouer, K. J., additional, McCullough, M. L., additional, Setiawan, V. W., additional, Shu, X.-O., additional, Weinstein, S. J., additional, Weiss, J. M., additional, Arslan, A. A., additional, De Vivo, I., additional, Gao, Y.-T., additional, Hayes, R. B., additional, Henderson, B. E., additional, Horst, R. L., additional, Koenig, K. L., additional, Patel, A. V., additional, Purdue, M. P., additional, Snyder, K., additional, Steplowski, E., additional, Yu, K., additional, Zheng, W., additional, and Hankinson, S. E., additional

Published
2010
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20. Circulating 25-Hydroxyvitamin D and the Risk of Rarer Cancers: Design and Methods of the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers

Author

Gallicchio, L., primary, Helzlsouer, K. J., additional, Chow, W.-H., additional, Freedman, D. M., additional, Hankinson, S. E., additional, Hartge, P., additional, Hartmuller, V., additional, Harvey, C., additional, Hayes, R. B., additional, Horst, R. L., additional, Koenig, K. L., additional, Kolonel, L. N., additional, Laden, F., additional, McCullough, M. L., additional, Parisi, D., additional, Purdue, M. P., additional, Shu, X.-O., additional, Snyder, K., additional, Stolzenberg-Solomon, R. Z., additional, Tworoger, S. S., additional, Varanasi, A., additional, Virtamo, J., additional, Wilkens, L. R., additional, Xiang, Y.-B., additional, Yu, K., additional, Zeleniuch-Jacquotte, A., additional, Zheng, W., additional, Abnet, C. C., additional, Albanes, D., additional, Bertrand, K., additional, and Weinstein, S. J., additional

Published
2010
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21. Overall and cancer related mortality among patients with ocular inflammation treated with immunosuppressive drugs: retrospective cohort study

Author

Kempen, J. H, primary, Daniel, E., additional, Dunn, J. P, additional, Foster, C S., additional, Gangaputra, S., additional, Hanish, A., additional, Helzlsouer, K. J, additional, Jabs, D. A, additional, Kacmaz, R O., additional, Levy-Clarke, G. A, additional, Liesegang, T. L, additional, Newcomb, C. W, additional, Nussenblatt, R. B, additional, Pujari, S. S, additional, Rosenbaum, J. T, additional, Suhler, E. B, additional, and Thorne, J. E, additional

Published
2009
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26. Nonmelanoma Skin Cancer and Risk for Subsequent Malignancy

Author

Chen, J., primary, Ruczinski, I., additional, Jorgensen, T. J., additional, Yenokyan, G., additional, Yao, Y., additional, Alani, R., additional, Liegeois, N. J., additional, Hoffman, S. C., additional, Hoffman-Bolton, J., additional, Strickland, P. T., additional, Helzlsouer, K. J., additional, and Alberg, A. J., additional

Published
2008
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31. 1,1-Dichloro-2,2-bis(p-chlorophenyl)ethylene and Polychlorinated Biphenyls and Breast Cancer: Combined Analysis of Five U.S. Studies

Author

Laden, F., primary, Collman, G., additional, Iwamoto, K., additional, Alberg, A. J., additional, Berkowitz, G. S., additional, Freudenheim, J. L., additional, Hankinson, S. E., additional, Helzlsouer, K. J., additional, Holford, T. R., additional, Huang, H.-Y., additional, Moysich, K. B., additional, Tessari, J. D., additional, Wolff, M. S., additional, Zheng, T., additional, and Hunter, D. J., additional

Published
2001
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37. Protective Alterations in Phase 1 and 2 Metabolism of Aflatoxin B1 by Oltipraz in Residents of Qidong, People's Republic of China

Author

Wang, J.-S., primary, Shen, X., additional, He, X., additional, Zhu, Y.-R., additional, Zhang, B.-C., additional, Wang, J.-B., additional, Qian, G.-S., additional, Kuang, S.-Y., additional, Zarba, A., additional, Egner, P. A., additional, Jacobson, L. P., additional, Munoz, A., additional, Helzlsouer, K. J., additional, Groopman, J. D., additional, and Kensler, T. W., additional

Published
1999
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41. Authors' reply

Author

Parkes, C., primary, Wald, N. J, additional, Murphy, P., additional, George, L., additional, Watt, H. C, additional, Kirby, R., additional, Knekt, P., additional, Helzlsouer, K J, additional, and Tuomilehto, J, additional

Published
1996
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45. Circulating sex hormones and breast cancer risk factors in postmenopausal women: reanalysis of 13 studies.

Author

Key, T. J., Appleby, P N, Reeves, G K, Roddam, A W, Helzlsouer, K J, Alberg, A J, Rollison, D E, Dorgan, J F, Brinton, L A, Overvad, K, Kaaks, R, Trichopoulou, A, Clavel-Chapelon, F, Panico, S, Duell, E J, Peeters, P H M, Rinaldi, S, Fentiman, I S, Dowsett, M, and Manjer, J

Subjects
SEX hormones, BREAST cancer, CANCER risk factors, OVARIECTOMY, POSTMENOPAUSE, TESTOSTERONE, CIGARETTE smokers, ANDROGENS
Abstract

Background: Breast cancer risk for postmenopausal women is positively associated with circulating concentrations of oestrogens and androgens, but the determinants of these hormones are not well understood.Methods: Cross-sectional analyses of breast cancer risk factors and circulating hormone concentrations in more than 6000 postmenopausal women controls in 13 prospective studies.Results: Concentrations of all hormones were lower in older than younger women, with the largest difference for dehydroepiandrosterone sulphate (DHEAS), whereas sex hormone-binding globulin (SHBG) was higher in the older women. Androgens were lower in women with bilateral ovariectomy than in naturally postmenopausal women, with the largest difference for free testosterone. All hormones were higher in obese than lean women, with the largest difference for free oestradiol, whereas SHBG was lower in obese women. Smokers of 15+ cigarettes per day had higher levels of all hormones than non-smokers, with the largest difference for testosterone. Drinkers of 20+ g alcohol per day had higher levels of all hormones, but lower SHBG, than non-drinkers, with the largest difference for DHEAS. Hormone concentrations were not strongly related to age at menarche, parity, age at first full-term pregnancy or family history of breast cancer.Conclusion: Sex hormone concentrations were strongly associated with several established or suspected risk factors for breast cancer, and may mediate the effects of these factors on breast cancer risk. [ABSTRACT FROM AUTHOR]

Published
2011
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46. The Reliability of Nipple Aspirate and Ductal Lavage in Women at Increased Risk for Breast Cancer--a Potential Tool for Breast Cancer Risk Assessment and Biomarker Evaluation.

Author

Visvanathan, K., Santor, D., Ali, S. Z., Brewster, A., Arnold, A., Armstrong, D. K., Davidson, N. E., and Helzlsouer, K. J.

Abstract

The article focuses on a study that evaluates the reliability of nipple aspirate (NAF) and ductal lavage in the assessment of breast cancer risk in women in Baltimore, Maryland. Ductal lavage is a method used to extract sample of epithelial cells from breast ducts. Samples of inadequate cellular material for diagnosis were significantly present in postmenopausal women compared with premenopausal women. The study concluded that the use of ductal lavage is limited by technical challenges.

Published
2007
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48. A prospective study of plasma ascorbic acid concentrations and breast cancer (United States).

Author

Wu, Kana, Helzlsouer, Kathy, Alberg, Anthony, Comstock, George, Norkus, Edward, Hoffman, Sandra, Wu, K, Helzlsouer, K J, Alberg, A J, Comstock, G W, Norkus, E P, and Hoffman, S C

Abstract

Objectives: To investigate the association between prediagnostic plasma ascorbic acid concentrations and subsequent breast cancer risk in a nested case-control study.Methods: Female volunteer residents of Washington County, MD, donated 14,625 non-fasting blood samples in 1989. Incident breast cancer cases (n = 115) and controls (n = 115) were matched by age, menopausal status at donation, and date and hour of blood donation.Results: Median ascorbic acid concentrations were similar between cases and controls (1.44 mg/dl vs. 1.39 mg/dl. p = 0.78). There was no evidence for a dose-response relationship between higher plasma ascorbic acid concentrations and breast cancer risk [highest vs. lowest fifths: ORadjusted = 0.90, Ptrend = 0.98).Conclusions: Findings from this prospective study do not suggest a protective association between prediagnostic plasma ascorbic acid concentrations and breast cancer risk in the subsequent 5 years of follow-up. [ABSTRACT FROM AUTHOR]

Published
2000
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49. Association between glutathione S-transferase M1, P1, and T1 genetic polymorphisms and development of breast cancer.

Author

Helzlsouer, K J, Selmin, O, Huang, H Y, Strickland, P T, Hoffman, S, Alberg, A J, Watson, M, Comstock, G W, and Bell, D

Subjects
*BREAST tumors, *COMPARATIVE studies, *DNA, *DNA probes, *GENETIC polymorphisms, *RESEARCH methodology, *MEDICAL cooperation, *PAIRED comparisons (Mathematics), *RESEARCH, *TRANSFERASES, *PERIMENOPAUSE, *LOGISTIC regression analysis, *EVALUATION research, *RELATIVE medical risk, *CASE-control method, *POSTMENOPAUSE, *ODDS ratio
Abstract

Background: Glutathione S-transferases (GSTs) are encoded by a superfamily of genes and play a role in the detoxification of potential carcinogens. In a nested case-control study, we investigated associations between genetic variability in specific GST genes (GSTM1, GSTT1, and GSTP1) and susceptibility to breast cancer.Methods: In 1989, a total of 32 898 individuals donated blood samples to a research specimen bank established in Washington County, MD. Genotypes of blood specimen DNA were determined for 110 of 115 women with incident cases of breast cancer diagnosed during the period from 1990 through 1995 and up to 113 of 115 control subjects. Associations between specific genotypes and the development of breast cancer were examined by use of logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs).Results: The GSTM1 homozygous null genotype was associated with an increased risk of developing breast cancer (OR = 2.10; 95% CI = 1.22-3.64), principally due to an association with postmenopausal breast cancer (OR = 2.50; 95% CI = 1.34-4.65). For GSTP1, the data were suggestive of a trend of increasing risk with higher numbers of codon 105 valine alleles (compared with isoleucine alleles); a 1.97-fold increased risk of breast cancer (95% CI = 0.77-5.02) was associated with valine/valine homozygosity. The risk of breast cancer associated with the GSTT1 homozygous null genotype was 1.50 (95 % CI = 0.76-2.95). The risk of breast cancer increased as the number of putative high-risk genotypes increased (P for trend <.001) (OR = 3.77; 95% CI = 1.10-12.88 for a combined genotype of GSTM1 null, GSTT1 null, and either GSTP1 valine heterozygosity or GSTP1 valine homozygosity).Conclusions: Our findings suggest that genetic variability in members of the GST gene family may be associated with an increased susceptibility to breast cancer. [ABSTRACT FROM AUTHOR]

Published
1998
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50. COMT genotype, micronutrients in the folate metabolic pathway and breast cancer risk.

Author

Goodman, J E, Lavigne, J A, Wu, K, Helzlsouer, K J, Strickland, P T, Selhub, J, and Yager, J D

Abstract

Catechol-O-methyltransferase (COMT) catalyzes the O-methylation of catechol estrogens (CEs), using S-adenosylmethionine (SAM) as a methyl donor. Several studies have indicated that the val108met COMT polymorphism, which results in a 3-4-fold decrease in activity, is associated with increased breast cancer risk. Folate, whose intake levels have also been associated with breast cancer risk, and other micronutrients in the folate metabolic pathway influence levels of SAM and S-adenosylhomocysteine (SAH), a COMT inhibitor generated by the demethylation of SAM. Because these micronutrients have been shown to alter SAM and SAH levels, we hypothesized that they could also affect COMT-catalyzed CE methylation. Although measurements of SAM and SAH were not initially collected, a secondary analysis of data from two nested case-control studies was performed to examine whether serum levels of folate, vitamin B12 (B12), pyridoxal 5'-phosphate (PLP), cysteine and homocysteine, in conjunction with COMT genotype, were associated with breast cancer risk. COMT(HH) (high activity COMT homozygote) breast cancer cases had statistically significantly lower levels of homocysteine (P = 0.05) and cysteine (P = 0.04) and higher levels of PLP (P = 0.02) than COMT(HH) controls. In contrast, COMT(LL) (low activity COMT homozygote) cases had higher levels of homocysteine than COMT(LL) controls (P = 0.05). No associations were seen between B12, COMT genotype, and breast cancer risk. An increasing number of COMT(L) alleles was significantly associated with increased breast cancer risk in women with below median levels of folate (P(trend) = 0.05) or above median levels of homocysteine (P(trend) = 0.02). These findings are consistent with a role for certain folate pathway micronutrients in mediating the association between COMT genotype and breast cancer risk.

Published
2001
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