Publications

 
Title: Influence of Vitamin A on Cervical Dysplasias and Carcinoma in Situ. Nutrition and Cancer 6(1):49 57.
Author:
Wylie Rosett, J.A., Romney, S.L., Slagle, N.S., Wassertheil Smoller, S., Miller, G.L., Palan, P.R., Lucido, D.L., Duttagupta, C.
Date:
1984
Title: Plasma Vitamin C and Uterine Cervical Dysplasia. American Journal of Obstetrics and Gynecology, 151:976 979.
Author:
Romney, S.L., Duttagupta, C., Basu, J., Palan, P.R., Karp, S., Slagle, S.N., Dwyer, A., Wassertheil Smoller, S., Wylie Rosett, J.
Date:
1985
Title: Cardiovascular Health and Risk Management: The Role of Nutrition and Medication in Clinical Practice, PSG, Publishing, Inc.
Author:
Edited by S. Wassertheil Smoller, M.H. Alderman and J. Wylie Rosett
Date:
1988
Title: The insulin-like growth factor (IGF)-axis in glucose homeostasis and type 2 diabetes
Author:
, S.N., Gunter, M.J., Wylie-Rosett, J., Kaplan, R.C., Muzumdar, R., Rohan, T.E., and Strickler, H.D
Publication:
Diabetes and Metabolism Research and Reviews
Date:
2008; In Press
Title: Body Iron stores and risk of developing Type II diabetes
Author:
Rajpathak, S.N., Wylie-Rosett, J., Gunter, M.J., Negassa, A., Kabat, G.C., Rohan, T.E., Crandall, J.
Publication:
Diabetes, Obesity and Metabolism
Date:
2008; In press
Title: A Prospective Evaluation of Insulin, insulin-like growth factor-I and risk of endometrial cancer.
Author:
Gunter, M.J., Hoover, D., Yu, H., Wassertheil-Smoller, S., Manson, J.E., Li, J., Harris, TG., Xue, X. Rohan, T.E., Ho, G.Y., Einstein, M.H., Anderson, G.L., Kaplan, R.C., Burk, R.D., Pollak, M.N., Howard, B.V and Strickler, H.D.
Abstract:
Obesity is a major risk factor for endometrial cancer; a relationship thought to largely be explained by the prevalence of high estrogen levels in obese women. Obesity is also associated with high levels of insulin, a known mitogen. However, no prospective studies have directly assessed whether insulin and/or insulin-like growth factor-I (IGF-I), a related hormone, are associated with endometrial cancer while accounting for estrogen levels. We, therefore, conducted a case-cohort study of incident endometrial cancer in the Women’s Health Initiative Observational Study, a prospective cohort of 93,676 postmenopausal women. The study involved all 250 incident cases, and a random subcohort of 465 subjects for comparison. Insulin, total IGF-I, free IGF-I, IGF binding protein-3, glucose and estradiol levels were measured in fasting baseline serum specimens. Cox models were used to estimate associations with endometrial cancer-particularly endometrioid adenocarcinomas (EA), the main histologic type (N=205). Our data showed that insulin levels were positively associated with EA (hazard ratio contrasting highest versus lowest quartile [HRq4-q1]=2.33, 95% confidence interval [CI],1.13 - 4.82), among women not using hormone therapy (HT), after adjustment for age and estradiol. Free IGF-I was inversely associated with EA (HRq4-q1=0.53, 95% CI, 0.31 - 0.90), after adjustment for age, HT use and estradiol. Both of these associations were stronger among overweight/obese women, especially the association between insulin and EA (HRq4-q1=4.30, 95% CI,1.62 -11.43). These data indicate that hyperinsulinemia may represent a risk factor for EA, that is independent of estradiol. Free IGF-I levels were inversely associated with EA, consistent with prior cross-sectional data.
Publication:
Cancer Epidemiology Biomarkers Prevention
Date:
2008; 17(4):921-9.
Title: Insulin, insulin-like growth factor-I, endogenous estradiol and colorectal cancer risk in postmenopausal women.
Author:
Gunter, M.J., Hoover, D., Yu, H., Wassertheil-Smoller, S., Manson, J.E., Li, J., Harris, TG., Xue, X. Rohan, T.E., Ho, G.Y., Anderson, G.L., Kaplan, R.C., Burk, R.D., Howard, B.V and Strickler, H.D.
Abstract:
Obesity is a risk factor for colorectal cancer, and hyperinsulinemia, a common condition in obese patients, may underlie this relationship. Insulin, in addition to its metabolic effects, has pro-mitotic and anti-apoptotic activity that may be tumorigenic. Insulin-like growth factor (IGF)-I, a related hormone, shares sequence homology with insulin, and has even stronger mitogenic effects. However, few prospective colorectal cancer studies directly measured fasting insulin, and none evaluated free IGF-I, or endogenous estradiol, a potential cofactor in postmenopausal women. Therefore, we conducted a case-cohort investigation of colorectal cancer among non-diabetic subjects enrolled in the Women’s Health Initiative (WHI) Observational Study, a prospective cohort of 93,676 postmenopausal women. Fasting baseline serum from all incident colorectal cancer cases (N=438) and a random subcohort (N=816) of WHI-OS subjects was tested for insulin, glucose, total IGF-I, free IGF-I, IGF binding protein-3, and estradiol. Comparing extreme quartiles, insulin [Hazard Ratio,HR,q4-q1]=1.73, 95% confidence interval[CI], 1.16-2.57; Ptrend=0.005), waist circumference (HRq4-q1=1.82, 95%CI, 1.22-2.70; Ptrend=0.001), and free IGF-I (HRq4-q1=1.35, 95%CI, 0.92-1.98; Ptrend=0.05) were each associated with colorectal cancer incidence in multivariate models. However, these associations each became non-significant when adjusted for one another. Endogenous estradiol levels, in contrast, were positively associated with risk of colorectal cancer (HR comparing high versus low levels =1.53, 95% CI, 1.05-2.22), even after control for insulin, free IGF-I, waist circumference. These data suggest the existence of at least two independent biologic pathways that are related to colorectal cancer: one that involves endogenous estradiol, and a second pathway broadly associated with obesity, hyperinsulinemia, and free IGF-I.
Publication:
Cancer Research
Date:
2008, 68(1): 329-37
Title: Insulin, Insulin-like growth factor-I and Breast Cancer Risk in Postmenopausal Women
Author:
Gunter, M.J., Hoover, D., Yu, H., Wassertheil-Smoller, S., Manson, J.E., Li, J., Harris, TG., Xue, X. Rohan, T.E., Ho, G.Y., Anderson, G.L., Kaplan, R.C., Burk, R.D., Howard, B.V and Strickler, H.D
Abstract:
Background: The positive association between obesity and postmenopausal breast cancer has been attributed, in part, to the fact that estrogen, a risk factor for breast cancer, is synthesized in adipose tissue. Obesity is also associated with high levels of insulin, a known mitogen. However, no prospective studies have directly assessed associations between circulating levels of insulin and/or insulin-like growth factor (IGF)-I, a related hormone, and the risk of breast cancer independent of estrogen level. Methods: We conducted a case–cohort study of incident breast cancer among nondiabetic women who were enrolled in the Women's Health Initiative Observational Study (WHI-OS), a prospective cohort of 93 676 postmenopausal women. Fasting serum samples obtained at study entry from 835 incident breast cancer case subjects and from a subcohort of 816 randomly chosen WHI-OS subjects were tested for levels of insulin, glucose, total IGF-I, free IGF-I, insulin-like growth factor binding protein-3, and estradiol. Multivariable Cox proportional hazards models were used to estimate associations between levels of the serologic factors and baseline characteristics (including body mass index [BMI]) and the risk of breast cancer. All statistical tests were two-sided. Results: Insulin levels were positively associated with the risk of breast cancer (hazard ratio [HR] for highest vs lowest quartile of insulin level = 1.46, 95% confidence interval [CI] = 1.00 to 2.13, Ptrend = .02); however, the association with insulin level varied by hormone therapy (HT) use (Pinteraction = .01). In a model that controlled for multiple breast cancer risk factors including estradiol, insulin level was associated with breast cancer only among nonusers of HT (HR for highest vs lowest quartile of insulin level = 2.40, 95% CI = 1.30 to 4.41, Ptrend < .001). Obesity (BMI 30 kg/m2) was also associated with the risk of breast cancer among nonusers of HT (HR for BMI 30 kg/m2 vs 18.5 to <25 kg/m2 = 2.12, 95% CI = 1.26 to 3.58, Ptrend = .003); however, this association was attenuated by adjustment for insulin (Ptrend = .40). Conclusion: These data suggest that hyperinsulinemia is an independent risk factor for breast cancer and may have a substantial role in explaining the obesity–breast cancer relationship.
Publication:
Journal of the National Cancer Institute
Date:
1/7/2009
Title: Alcohol consumption and the risk of coronary heart disease in postmenopausal women with diabetes: Women's Health Initiative Observational Study
Author:
Rajpathak SN, Freiberg MS, Wang C, Wylie-Rosett J, Wildman RP, Rohan TE, Robinson
Abstract:
BACKGROUND: Although several observational studies have consistently reported an inverse association between moderate alcohol consumption and risk of coronary heart disease (CHD), it is yet not well established if this association also exists among people with type 2 diabetes. The aim of this study is to evaluate the association between the frequency and quantity of alcohol intake and the risk of developing CHD among postmenopausal women with diabetes. METHODS: We conducted a prospective cohort study, which included 3,198 women with self-reported diabetes and without any history of cardiovascular disease at baseline, in the Women's Health Initiative Observational Study. Alcohol intake was assessed by a semiquantitative food frequency questionnaire. The primary outcome of this study was CHD, which was validated by medical record review. Cox proportional hazards regression was used to estimate the hazard ratio (HR) for the association of alcohol intake and risk of incident CHD while adjusting for several potential confounders. RESULTS: During the 22,546 person-years of follow-up, there were 336 incident cases of CHD. Both frequency and quantity of alcohol intake were inversely associated with the risk of developing CHD. Compared to nondrinkers, the multivariable HRs across categories of frequency of alcohol consumption (or=2 drinks/week) were 0.89 (95% confidence intervals [CI]: 0.63, 1.26), 0.84 (95% CI: 0.56, 1.25) and 0.65 (95% CI: 0.43, 0.99), respectively (p for trend: 0.04). This association did not appear to differ based on the type of the alcoholic beverage consumed. CONCLUSIONS: Moderate alcohol consumption of postmenopausal women with type 2 diabetes may have a benefit on CHD similar to that seen in postmenopausal nondiabetic women. The potential risks of alcohol on noncardiac outcomes may need consideration when recommending alcohol to women with diabetes.
Publication:
European Journal of Nutrition