A major emphasis of this project has been to define the relationship of exogenous hormones to subsequent cancer risk. Recent analyses have assesed the relationships of menopausal hormones to gynecologic and breast cancer risk using data from our large, prospective cohort studies. Using data from the NIH-AARP Diet and Health Cohort Study, we have clarified some unresolved issues regarding ovarian cancer risk in women who use menopausal hormone therapy. Increased ovarian cancer risks among women who used unopposed estrogen therapy for 10 or more years provide further evidence to support the hypothesis that increased estrogen levels after menopause can influence the development of ovarian cancer. In addition, this study provided some of the first strong evidence that specifically links estrogen plus progestin use to increased ovarian cancer risk in women with intact uteri. These results reiterate the value of long-term follow-up of existing cohorts to elucidate increased risks of rare outcomes, such as ovarian cancer, among women exposed to menopausal hormone therapy. This large cohort study has also been used to assess relationships of menopausal hormones to the risk of endometrial cancers. In contrast to some previous suggestions that estrogen plus progestin therapy might protect against this cancer, we found no evidence for such protection. In fact, we found evidence that women who used progestins sequentially, particularly for long periods of time, might be at an increased risk of developing endometrial cancer compared to non-users. Further, within this same study we examined risks of breast cancer related to both estrogens alone and with combined estrogen-progestin therapy. This investigation found elevated risks for both types of preparations, although combined therapy was more strongly related. Hormone effects were stronger among thin women, but combined therapy continued to be a risk factor even among heavy women. Finally, data were used to assess whether hormones had differential relationships on different types of tumors. The strongest effects were seen for estrogen receptor positive tumors, and these relations affected other clinical parameters, including histology. These analyses stressed the importance of considering joint clinical parameters when assessing hormone effects. In contrast to the relationships observed for breast and gynecologic cancers, we observed no relationship of hormone therapy to lung cancer risk, as had been suggested by some earlier studies.The AARP study has also been useful for evaluating effects on cancer risk of other medications. Analyses have assessed breast, endometrial and liver cancer risk in relation to non-steroidal anti-inflammatory drugs (NSAIDs), stimulated by some research that has suggested an important role for inflammation in the etiology of these cancer sites. There were suggestions for all three of these cancer site that NSAID use might reduce risk, although the relationships with the drugs used were somewhat different across cancer sites. We are also evaluating risk of testicular cancer in relation to certain cholesterol-lowering and diabetic medications.Recent cohort studies demonstrated reduced breast cancer risks among women with a history of fractures or low bone mineral density. The impact of the severity and timing of bone loss on risk has not yet been investigated, and the extent to which other risk factors (family history, anthropometric factors, physical activity, and exogenous hormones) modify the relationship with bone density is unknown. To elaborate on these research questions, we have conducted a follow-up study of over 20,000 postmenopausal women who volunteered for a clinical trial of the bone-enhancing drug alendronate. This large cohort includes extensive baseline information on major breast cancer risk factors, and thus is ideal for evaluating potential interactions with bone mineral density and the effects of bone mineral density on other cancer sites. The availability of serologic samples from study participants will also enable assessment of the interactive effects of endogenous hormones and bone mineral density on subsequent breast cancer risk.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Investigator-Initiated Intramural Research Projects (ZIA)
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Division of Cancer Epidemiology and Genetics
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Dallal, Cher M; Lacey Jr, James V; Pfeiffer, Ruth M et al. (2016) Estrogen Metabolism and Risk of Postmenopausal Endometrial and Ovarian Cancer: the B ∼ FIT Cohort. Horm Cancer 7:49-64
Reigstad, Marte Myhre; Larsen, Inger Kristin; Myklebust, Tor Ã…ge et al. (2016) Risk of Cancer in Children Conceived by Assisted Reproductive Technology. Pediatrics 137:e20152061
Reigstad, M M; Larsen, I K; Myklebust, T Ã… et al. (2015) Cancer risk among parous women following assisted reproductive technology. Hum Reprod 30:1952-63
Brinton, Louise A; Moghissi, Kamran S; Scoccia, Bert et al. (2015) Effects of fertility drugs on cancers other than breast and gynecologic malignancies. Fertil Steril 104:980-8
Key, T J; Appleby, P N; Reeves, G K et al. (2015) 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. Steroids 99:49-55
Falk, Roni T; Dallal, Cher M; Lacey Jr, James V et al. (2015) Estrogen Metabolites Are Not Associated with Colorectal Cancer Risk in Postmenopausal Women. Cancer Epidemiol Biomarkers Prev 24:1419-22
Dallal, Cher M; Tice, Jeffrey A; Buist, Diana S M et al. (2014) Estrogen metabolism and breast cancer risk among postmenopausal women: a case-cohort study within B~FIT. Carcinogenesis 35:346-55
Trabert, Britton; Lamb, Emmet J; Scoccia, Bert et al. (2013) Ovulation-inducing drugs and ovarian cancer risk: results from an extended follow-up of a large United States infertility cohort. Fertil Steril 100:1660-6
Hargreave, Marie; Jensen, Allan; Deltour, Isabelle et al. (2013) Increased risk for cancer among offspring of women with fertility problems. Int J Cancer 133:1180-6
Brinton, Louise A; Westhoff, Carolyn L; Scoccia, Bert et al. (2013) Fertility drugs and endometrial cancer risk: results from an extended follow-up of a large infertility cohort. Hum Reprod 28:2813-21

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