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1.  Body size and the risk of endometrial cancer by hormone therapy use in postmenopausal women in the California Teachers Study cohort 
Cancer causes & control : CCC  2010;21(9):1407-1416.
To investigate whether hormone therapy (HT) and obesity are associated with endometrial cancer risk among postmenopausal women in the California Teachers Study cohort.
Of 28,418 postmenopausal women, 395 developed type 1 endometrial cancer between 1995 and 2006. Multivariate Cox regression was performed to estimate relative risks (RR), stratified by HT use (never used, ever estrogen-alone (ET), or exclusively estrogen-plus-progestin (EPT)).
Among women who never used HT, overall and abdominal adiposity were associated with increased risk; when evaluated simultaneously, abdominal adiposity was more strongly associated (RR 2.2, 95% confidence interval (CI): 1.1–4.5 for waist ≥35 vs. <35 inches). Among women who ever used ET, risk was increased in women with BMI ≥25 kg/m2 (RR 1.6, 95% CI: 1.1–2.3 vs. <25 kg/m2). Neither overall nor abdominal obesity was associated with risk in women who exclusively used EPT (P-interaction<0.001 for BMI by HT use).
Among women who never used HT, risk was strongly positively related to obesity and may have been influenced more by abdominal than overall adiposity; however, due to small numbers, this latter finding requires replication. Among women who ever used ET, being overweight at baseline predicted higher risk, whereas use of EPT mitigated any effect of obesity.
PMCID: PMC2925506  PMID: 20431936
endometrial cancer; obesity; abdominal adiposity; hormone therapy
2.  Wine and other alcohol consumption and risk of ovarian cancer in the California Teachers Study cohort 
Cancer Causes & Control  2007;18(1):91-103.
Whether alcohol consumption influences ovarian cancer risk is unclear. Therefore, we investigated the association between alcohol intake at various ages and risk of ovarian cancer.
Among 90,371 eligible members of the California Teachers Study cohort who completed a baseline alcohol assessment in 1995–1996, 253 women were diagnosed with epithelial ovarian cancer by the end of 2003. Multivariate Cox proportional hazards regression analysis was performed to estimate relative risks (RRs) and 95% confidence intervals (CIs).
Consumption of total alcohol, beer, or liquor in the year prior to baseline, at ages 30–35 years, or at ages 18–22 years was not associated with risk of ovarian cancer. Consumption of at least one glass per day of wine, compared to no wine, in the year before baseline was associated with increased risk of developing ovarian cancer: RR = 1.57 (95% CI 1.11–2.22), Ptrend = 0.01. The association with wine intake at baseline was particularly strong among peri-/post-menopausal women who used estrogen-only hormone therapy and women of high socioeconomic status.
Alcohol intake does not appear to affect ovarian cancer risk. Constituents of wine other than alcohol or, more likely, unmeasured determinants of wine drinking were associated with increased risk of ovarian cancer.
PMCID: PMC1764867  PMID: 17186425
Ovarian cancer; Alcoholic beverages; Cohort studies; Women’s health
3.  Diet and Risk of Ovarian Cancer in the California Teachers Study Cohort 
American journal of epidemiology  2007;165(7):802-813.
Dietary phytochemical compounds, including isoflavones and isothiocyanates, may inhibit cancer development but have not yet been examined in prospective epidemiologic studies of ovarian cancer. The authors have investigated the association between consumption of these and other nutrients and ovarian cancer risk in a prospective cohort study. Among 97,275 eligible women in the California Teachers Study cohort who completed the baseline dietary assessment in 1995–1996, 280 women developed invasive or borderline ovarian cancer by December 31, 2003. Multivariable Cox proportional hazards regression, with age as the timescale, was used to estimate relative risks and 95% confidence intervals; all statistical tests were two sided. Intake of isoflavones was associated with lower risk of ovarian cancer. Compared with the risk for women who consumed less than 1 mg of total isoflavones per day, the relative risk of ovarian cancer associated with consumption of more than 3 mg/day was 0.56 (95% confidence interval: 0.33, 0.96). Intake of isothiocyanates or foods high in isothiocyanates was not associated with ovarian cancer risk, nor was intake of macronutrients, antioxidant vitamins, or other micronutrients. Although dietary consumption of isoflavones may be associated with decreased ovarian cancer risk, most dietary factors are unlikely to play a major role in ovarian cancer development.
PMCID: PMC2093945  PMID: 17210953
antioxidants; cohort studies; diet; isoflavones; isothiocyanates; nutrition; ovarian neoplasms; women's health
4.  Dietary patterns and risk of ovarian cancer in the California Teachers Study cohort 
Nutrition and cancer  2008;60(3):285-291.
Previous studies have examined the association between individual foods or nutrients, but not overall diet, and ovarian cancer risk. To account for the clustering of foods in the diet, we investigated the association between dietary patterns and risk of ovarian cancer in the prospective California Teachers Study cohort. Of 97,292 eligible women who completed the baseline dietary assessment in 1995–1996, 311 women developed epithelial ovarian cancer on or before December 31, 2004. Based on principal components analysis, five major dietary patterns were identified and termed “plant-based,” “high-protein/high-fat,” “high-carbohydrate,” “ethnic,” and “salad-and-wine.” Multivariable Cox proportional hazards regression analysis was used to estimate associations between these dietary patterns and risk of incident ovarian cancer. Most of the dietary patterns were not significantly associated with ovarian cancer risk. However, women who followed a plant-based diet had higher risk; comparing those in the top quintile of plant-based food intake with those in the lowest quintile, the relative risk of ovarian cancer was 1.65 (95% confidence interval: 1.07–2.54; Ptrend=0.03). Associations with the five dietary patterns did not vary by known ovarian cancer risk factors or other behavioral or sociodemographic characteristics. Overall, our results show no convincing associations between dietary patterns and ovarian cancer risk.
PMCID: PMC2365491  PMID: 18444162
5.  Several anthropometric measurements and breast cancer risk: results of the E3N cohort study 
International Journal of Obesity  2006;30(1):156-163.
To investigate the association between various anthropometric characteristics and breast cancer.
Longitudinal prospective cohort study. Follow-up between 1995 and 2000.
In total, 69 116 women (age: 45–70 years; mean follow-up: 3.6 years), 275 premenopausal and 860 postmenopausal incident invasive breast cancers.
Self-reported height, weight, breast, thorax, waist and hip circumferences and calculated body mass index (BMI) and waist-to-hip ratio (WHR) at baseline.
A slight increase in risk with increasing height was found. Weight, BMI, thorax and waist circumferences and WHR were negatively related to breast cancer risk among premenopausal women. The relationships became non significant after additional adjustment for BMI. An increased risk of premenopausal breast cancer with an android body shape (WHR>0.87) might possibly be confined to obese women. Among postmenopausal women, all anthropometric measurements of corpulence were positively associated with breast cancer risk but became non significant after additional adjustment for BMI. No difference in risk of postmenopausal breast cancer according to HRT use was observed.
The study confirmed that adiposity was negatively associated to premenopausal breast cancer risk and positively associated to postmenopausal breast cancer risk. Further studies will be needed to specify clearly the association between WHR and breast cancer risk, particularly before menopause.
PMCID: PMC1903368  PMID: 16231021
Adiposity; Aged; Anthropometry; Body Constitution; Body Height; Body Mass Index; Breast Neoplasms; Etiology; Epidemiologic Methods; Female; Humans; Middle Aged; Obesity; Complications; Postmenopause; Premenopause; Reproductive History; anthropometry; breast cancer; HRT use; cohort study; overweight
Results from studies examining the association between hormone therapy (HT) and lung cancer risk disagree.
We examined the associations between HT use and lung cancer risk among 60,592 postmenopausal women enrolled in the prospective California Teachers Study cohort. Between 1995 and 2007, 727 women were diagnosed with lung cancer. Multivariable Cox proportional hazards regression models were fit using age as the time metric.
No measure of HT use was associated with lung cancer risk (all p-values for trend≥0.4). In addition, no variations in risk by smoking status (never, ever, former, current), type of HT (E-alone, E+P use), type of menopause, or lung cancer histology were observed.
Our findings do not support an association between HT and lung cancer.
This large-scale, prospective study, which capitalizes on the detailed hormone use, smoking history, and type of menopause information available within this unique cohort, was unable to find any association between intake of HT and lung cancer risk.
PMCID: PMC3065239  PMID: 21266521
7.  Anthropometric measures and risk of epithelial ovarian cancer: results from the Nurses’ Health Study 
Obesity (Silver Spring, Md.)  2009;18(8):1625-1631.
Epidemiologic evaluations of the relationship between anthropometry and ovarian cancer risk have not been conclusive. Using data collected from two large cohorts, the Nurses’ Health Study (NHS) and NHSII, we prospectively evaluated the association between waist and hip circumference, the waist-to-hip ratio (WHR), and body mass index (BMI) with risk of epithelial ovarian cancer. Women completed biennial questionnaires assessing ovarian cancer risk factors beginning in 1976 (NHS) and 1989 (NHSII). For the WHR and BMI analyses, 333 and 862 confirmed cases were identified, respectively, through June 1, 2006 (NHS) and June 1, 2005 (NHSII). WHR and waist circumference were not associated with risk (P-trend=0.63 and 0.65, respectively). There was evidence for a decreased risk with increasing hip circumference among post-(P-trend=0.03), but a suggestive positive association among premenopausal women (P-trend=0.04) (P-interaction = 0.01). The hazard ratios comparing the highest versus lowest quintile of hip circumference among pre- and postmenopausal women were 1.54 (95% confidence interval [CI]=0.45–5.23) and 0.66 (95% CI=0.37–1.16), respectively. BMI was not clearly associated with risk in pre- or postmenopausal women. Results from this large prospective study suggest that hip circumference could be a possible risk factor for premenopausal ovarian cancer, but may reduce risk of postmenopausal ovarian cancer. The differential effect of hip circumference based on menopausal status requires further confirmation.
PMCID: PMC2888954  PMID: 20035276
cancer; BMI; waist circumference
8.  Oral contraceptives, menopausal hormone therapy use and risk of B-cell non-Hodgkin lymphoma in the California Teachers Study 
We examined oral contraceptive (OC) and menopausal hormonal therapy (MHT) use in relation to risk of B-cell non-Hodgkin lymphoma (NHL). Women under age 85 years participating in the California Teachers Study with no history of hematopoietic cancer were followed from 1995 through 2007. 516 of 114,131 women eligible for OC use analysis and 402 of 54,758 postmenopausal women eligible for MHT use analysis developed B-cell NHL. Multivariable adjusted and stratified Cox proportional hazards models were fit to estimate relative risks (RR) and 95% confidence intervals (95% CI). Ever versus never OC use was marginally associated with lower B-cell NHL risk, particularly among women first using OCs before age 25 years (RR=0.72, 95%CI=0.51-0.99); yet, no duration-response effect was observed. No association was observed for ever versus never MHT use among postmenopausal women (RR=1.05, 95%CI=0.83-1.33) overall, or by formulation (estrogen alone, ET, or estrogen plus progestin, EPT). Among women with no MHT use, having bilateral oophorectomy plus hysterectomy was associated with greater B-cell NHL risk than having natural menopause (RR=3.15, 95%CI=1.62-6.13). Bilateral oophorectomy plus hysterectomy was not associated with risk among women who used ET or EPT. These results indicate that exogenous hormone use does not strongly influence B-cell NHL risk.
PMCID: PMC3258672  PMID: 20957632
non-Hodgkin lymphoma; oral contraceptives; menopausal hormonal therapy; hysterectomy; bilateral oophorectomy
9.  Menopausal hormone therapy and subsequent risk of specific invasive breast cancer subtypes in the California Teachers Study 
Although it is well established that combined estrogen-progestin therapy (EPT) increases breast cancer risk, questions remain regarding the impact of different formulations of hormones, whether certain women are at particularly high risk, and whether risk varies by tumor subtype.
We investigated hormone therapy (HT) use in relation to breast cancer risk in the California Teachers Study cohort; after a mean follow-up of 9.8 years 2,857 invasive breast cancers were diagnosed.
Compared to women who had never used HT, women who reported 15 or more years of estrogen therapy (ET) use had 19% greater risk of breast cancer (95% Confidence Interval (CI), 1.03-1.37), while women using EPT for 15 or more years had 83% greater risk (95% CI, 1.48-2.26). Breast cancer risk was highest among women using continuous combined EPT regimens. Risks associated with EPT and ET use were increased with duration of HT use for women with body mass index (BMI)<29.9 kg/m2 but not for women with BMI≥30 kg/m2. Elevated risks associated with EPT and ET use were confined to tumors that were positive for both estrogen and progesterone receptors and those that were HER2+ but were slightly diminished for HER2- tumors.
Breast cancer risks increased with longer duration of ET and EPT use, and risks were highest for continuous-combined EPT use. Further, risks varied by BMI and tumor subtype.
These findings underscore the need for personalized risk-benefit discussions with women contemplating HT use.
PMCID: PMC2936672  PMID: 20699377
10.  Body Size and the Risk of Postmenopausal Breast Cancer Subtypes in the California Teachers Study Cohort 
Cancer causes & control : CCC  2012;10.1007/s10552-012-9897-x.
To evaluate how the association between body size and breast cancer risk varies by tumor receptor subtype, host factors and other exposures among women in the California Teacher Study cohort.
Among 52,642 postmenopausal women, 2,321 developed invasive breast cancer with known estrogen- and progesterone-receptor status (1,652 ER+PR+, 338 ER+PR−, 312 ER−PR−) between 1995 and 2007. In a subset of 35,529 with waist circumference data, 1,377 developed invasive breast cancer with known ERPR status (991 ER+PR+, 208 ER+PR−, 169 ER−PR−) between 1997 and 2007. Multivariate Cox regression was performed to estimate relative risks (RR) and 95% confidence intervals (CI).
Obesity, adult weight gain of ≥40 pounds, greater abdominal adiposity and greater height increased risk of ER+PR+ breast cancer. The increased risk associated with postmenopausal obesity was limited to those who did not use hormone therapy (HT) at cohort entry (RR=1.37, 95% CI: 1.05–1.78 for BMI ≥30 vs. <25 kg/m2; P-interaction=0.14) and those who were not overweight or obese at age 18 (P-interaction=0.06). The increased risk associated with greater abdominal adiposity was limited to those who were not also overweight or obese (P-interaction=0.01). Neither obesity, abdominal adiposity nor height were associated with the risk of ER−PR− tumors.
The effects of body size on postmenopausal breast cancer risk differed by hormone receptor subtype, and among women with ER+PR+ tumors, by HT use and early adult body size.
PMCID: PMC3366039  PMID: 22286371
breast cancer; obesity; hormone receptor status; abdominal adiposity; hormone therapy
11.  Ovarian Cancer Incidence Trends in Relation to Changing Patterns of Menopausal Hormone Therapy Use in the United States 
Journal of Clinical Oncology  2013;31(17):2146-2151.
After a report from the Women's Health Initiative (WHI) in 2002, a precipitous decline in menopausal hormonal therapy (MHT) use in the United States was linked to a decline in breast cancer incidence rates. Given that MHT use is also associated with increased ovarian cancer risk, we tested whether ovarian cancer incidence rates changed after 2002.
Using the North American Association of Central Cancer Registries database (1995 to 2008; N = 171,142 incident ovarian cancers), we applied standard analytic approaches and age-period-cohort (APC) models to estimate ovarian cancer incidence rate changes before (1995 to 2002) and after (2003 to 2008) the WHI report.
Among women age ≥ 50 years, age-standardized ovarian cancer incidence declined by 0.8% per year (95% CI, −1.8% to −0.5% per year) before the WHI announcement; after the WHI report, the rate declined by 2.4% per year (95% CI, −2.5% to −2.2% per year). APC models confirmed an accelerated decline in ovarian cancer incidence after the WHI report, adjusted for age and birth cohort effects. This sudden change was notable among women most likely to have used MHT (ie, women age 50 to 69 years, white women, and residents of regions with highest MHT prescription frequency). The largest changes were found for the endometrioid histologic subtype.
After a marked reduction in MHT use around 2002, ovarian cancer incidence rates demonstrated an accelerated decline, with the largest changes for endometrioid carcinomas. This strong temporal association, although not proving a causal role of hormones in ovarian carcinogenesis, suggests that future analytic research supporting cancer control efforts should clarify the role of hormonal exposures on the development and behavior of subtypes of ovarian cancer.
PMCID: PMC3731982  PMID: 23650423
12.  Body mass index and risk of ovarian cancer 
Cancer  2009;115(4):812-822.
Convincing epidemiologic evidence links excess body mass to increased risks of endometrial and postmenopausal breast cancers but the relation of body mass index (BMI) to ovarian cancer risk remains inconclusive. Potential similarities regarding a hormonal mechanism in the etiology of female cancers highlight the importance of investigating associations according to menopausal hormone therapy (MHT) use. However, data addressing whether the relation of BMI to ovarian cancer differs by MHT use are very sparse. We prospectively investigated the association between BMI and ovarian cancer among 94,525 U.S. women, followed from 1996–1997 to December 31, 2003. During 7 years of follow-up, we documented 303 epithelial ovarian cancer cases. As compared with normal weight women (BMI 18.5–24.9 kg/m2), the multivariate relative risk (MVRR) of ovarian cancer for obese women (BMI ≥30 kg/m2) in the cohort as a whole was 1.25 (95%-CI=0.93–1.68). Among women who never used MHT, the MVRR for obese versus normal weight women was 1.80 (95%-CI=1.16–2.80). In contrast, no relation between BMI and ovarian cancer was apparent among women who ever used MHT (MVRR=0.96; 95%-CI=0.64–1.43; P-interaction=0.02). Exploratory analyses also suggested a positive association between BMI and ovarian cancer among women without a family history of ovarian cancer (MVRR comparing obese versus normal weight women=1.36; 95%-CI=0.99–1.85), but no relation with BMI was apparent among women with a positive family history of ovarian cancer (MVRR=0.73; 95%-CI=0.34–1.60; P-interaction=0.02). We suspect that obesity is associated with enhanced ovarian cancer risk through a hormonal mechanism.
PMCID: PMC3507338  PMID: 19127552
13.  General and Abdominal Obesity and Risk of Death among Black Women 
The New England journal of medicine  2011;365(10):901-908.
Recent pooled analyses show an increased risk of death with increasing levels of the body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) of 25.0 or higher in populations of European ancestry, a weaker association among East Asians, and no association of an increased BMI with an increased risk of death among South Asians. The limited data available on blacks indicate that the risk of death is increased only at very high levels of BMI (≥35.0).
We prospectively assessed the relation of both BMI and waist circumference to the risk of death among 51,695 black women with no history of cancer or cardiovascular disease who were 21 to 69 years of age at study enrollment. Our analysis was based on follow-up data from 1995 through 2008 in the Black Women’s Health Study. Multivariable proportional-hazards models were used to estimate hazard ratios and 95% confidence intervals.
Of 1773 deaths identified during follow-up, 770 occurred among 33,916 women who had never smoked. Among nonsmokers, the risk of death was lowest for a BMI of 20.0 to 24.9. For a BMI above this range, the risk of death increased as the BMI increased. With a BMI of 22.5 to 24.9 as the reference category, multivariable-adjusted hazard ratios were 1.12 (95% confidence interval [CI], 0.87 to 1.44) for a BMI of 25.0 to 27.4, 1.31 (95% CI, 1.01 to 1.72) for a BMI of 27.5 to 29.9, 1.27 (95% CI, 0.99 to 1.64) for a BMI of 30.0 to 34.9, 1.51 (95% CI, 1.13 to 2.02) for a BMI of 35.0 to 39.9, and 2.19 (95% CI, 1.62 to 2.95) for a BMI of 40.0 to 49.9 (P<0.001 for trend). A large waist circumference was associated with an increased risk of death from any cause among women with a BMI of less than 30.0.
The risk of death from any cause among black women increased with an increasing BMI of 25.0 or higher, which is similar to the pattern observed among whites. Waist circumference appeared to be associated with an increased risk of death only among nonobese women. (Funded by the National Cancer Institute.)
PMCID: PMC3206314  PMID: 21899451
14.  Adult weight gain, fat distribution and mammographic density in Spanish pre- and post-menopausal women (DDM-Spain) 
High mammographic density (MD) is a phenotype risk marker for breast cancer. Body mass index (BMI) is inversely associated with MD, with the breast being a fat storage site. We investigated the influence of abdominal fat distribution and adult weight gain on MD, taking age, BMI and other confounders into account. Because visceral adiposity and BMI are associated with breast cancer only after menopause, differences in pre- and post-menopausal women were also explored. We recruited 3,584 women aged 45–68 years within the Spanish breast cancer screening network. Demographic, reproductive, family and personal history data were collected by purpose-trained staff, who measured current weight, height, waist and hip circumferences under the same protocol and with the same tools. MD was assessed in the left craniocaudal view using Boyd’s Semiquantitative Scale. Association between waist-to-hip ratio, adult weight gain (difference between current weight and self-reported weight at 18 years) and MD was quantified by ordinal logistic regression, with random center-specific intercepts. Models were adjusted for age, BMI, breast size, time since menopause, parity, family history of breast cancer and hormonal replacement therapy use. Natural splines were used to describe the shape of the relationship between these two variables and MD. Waist-to-hip ratio was inversely associated with MD, and the effect was more pronounced in pre-menopausal (OR = 0.53 per 0.1 units; 95 % CI = 0.42–0.66) than in post-menopausal women (OR = 0.73; 95 % CI = 0.65–0.82) (P of heterogeneity = 0.010). In contrast, adult weight gain displayed a positive association with MD, which was similar in both groups (OR = 1.17 per 6 kg; 95 % CI = 1.11–1.23). Women who had gained more than 24 kg displayed higher MD (OR = 2.05; 95 % CI = 1.53–2.73). MD was also evaluated using Wolfe’s and Tabár’s classifications, with similar results being obtained. Once BMI, fat distribution and other confounders were considered, our results showed a clear dose–response gradient between the number of kg gained during adulthood and the proportion of dense tissue in the breast.
PMCID: PMC3401511  PMID: 22689088
Mammographic density; Adult weight gain; Fat distribution; Breast cancer
15.  Menopausal Hormone Therapy Use and Risk of Invasive Colon Cancer 
American Journal of Epidemiology  2010;171(4):415-425.
Results from epidemiologic studies of hormone therapy use and colon cancer risk are inconsistent. This question was investigated in the California Teachers Study (1995–2006) among 56,864 perimenopausal or postmenopausal participants under 80 years of age with no prior colorectal cancer by using Cox proportional hazards regression. Incident invasive colon cancer was diagnosed among 442 participants. Baseline-recent hormone therapy users were at 36% lower risk for colon cancer versus baseline-never users (baseline-recent users: relative risk (RR) = 0.64, 95% confidence interval (CI): 0.51, 0.80). Results did not differ by formulation. Estimated risk was lower among baseline-recent hormone therapy users with increasing duration between 5 and 15 years of use (RR = 0.49, 95% CI: 0.35, 0.68), but the trend did not persist in the longest duration group, more than 15 years of use (RR = 0.69, 95% CI: 0.52, 0.92; Ptrend = 0.60). Long-term recreational physical activity, obesity, regular use of nonsteroidal antiinflammatory medications, and daily alcohol intake did not modify these effects; baseline-recent use was more strongly associated with colon cancer risk among women with a family history of colorectal cancer (Pheterogeneity = 0.04). Baseline-recent hormone therapy use was inversely associated with invasive colon cancer risk among perimenopausal and postmenopausal women in the California Teachers Study.
PMCID: PMC2842195  PMID: 20067917
colonic neoplasms; hormone replacement therapy; lung neoplasms; parity; prospective studies; reproduction; smoking
16.  Influence of Body Size and Body Fat Distribution on Risk of Uterine Leiomyomata in U.S. Black Women 
Epidemiology (Cambridge, Mass.)  2005;16(3):346-354.
Uterine leiomyomata are a major source of morbidity in black women. We prospectively investigated the risk of self-reported uterine leiomyomata in relation to body mass index (BMI), weight change, height, waist and hip circumferences, and waist-to-hip ratio in a large cohort of U.S black women.
Data were derived from the Black Women’s Health Study, a U.S. prospective cohort study of black women who complete biannual mailed health questionnaires. From 1997 through 2001, we followed 21,506 premenopausal women with intact uteri and no prior diagnosis of uterine leiomyomata. Cox regression models were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CIs).
After 70,345 person-years of follow up, 2146 new cases of uterine leiomyomata confirmed by ultrasound (n = 1885) or hysterectomy (n = 261) were self-reported. Compared with the thinnest women (BMI <20.0 kg/m2), the multivariate IRRs for women with BMIs of 20.0–22.4, 22.5–24.9, 25.0–27.4, 27.5–29.9, 30.0–32.4, and 32.5= kg/m2 were 1.34 (95% CI = 1.02–1.75), 1.39 (1.07–1.81), 1.45 (1.12–1.89), 1.47 (1.11–1.93), 1.36 (1.02–1.80), and 1.21 (0.93–1.58), respectively. IRRs were larger among parous women. Weight gain since age 18 was positively associated with risk, but only among parous women. No other anthropometric measures were associated with risk.
BMI and weight gain exhibited a complex relation with risk of uterine leiomyomata in the Black Women’s Health Study. The BMI association was inverse J-shaped and findings were stronger in parous women. Weight gain was positively associated with risk among parous women only.
PMCID: PMC1847589  PMID: 15824551
17.  Adiposity, hormone replacement therapy use and breast cancer risk by age and hormone receptor status: a large prospective cohort study 
Associations of hormone-receptor positive breast cancer with excess adiposity are reasonably well characterized; however, uncertainty remains regarding the association of body mass index (BMI) with hormone-receptor negative malignancies, and possible interactions by hormone replacement therapy (HRT) use.
Within the European EPIC cohort, Cox proportional hazards models were used to describe the relationship of BMI, waist and hip circumferences with risk of estrogen-receptor (ER) negative and progesterone-receptor (PR) negative (n = 1,021) and ER+PR+ (n = 3,586) breast tumors within five-year age bands. Among postmenopausal women, the joint effects of BMI and HRT use were analyzed.
For risk of ER-PR- tumors, there was no association of BMI across the age bands. However, when analyses were restricted to postmenopausal HRT never users, a positive risk association with BMI (third versus first tertile HR = 1.47 (1.01 to 2.15)) was observed. BMI was inversely associated with ER+PR+ tumors among women aged ≤49 years (per 5 kg/m2 increase, HR = 0.79 (95%CI 0.68 to 0.91)), and positively associated with risk among women ≥65 years (HR = 1.25 (1.16 to 1.34)). Adjusting for BMI, waist and hip circumferences showed no further associations with risks of breast cancer subtypes. Current use of HRT was significantly associated with an increased risk of receptor-negative (HRT current use compared to HRT never use HR: 1.30 (1.05 to 1.62)) and positive tumors (HR: 1.74 (1.56 to 1.95)), although this risk increase was weaker for ER-PR- disease (Phet = 0.035). The association of HRT was significantly stronger in the leaner women (BMI ≤22.5 kg/m2) than for more overweight women (BMI ≥25.9 kg/m2) for, both, ER-PR- (HR: 1.74 (1.15 to 2.63)) and ER+PR+ (HR: 2.33 (1.84 to 2.92)) breast cancer and was not restricted to any particular HRT regime.
An elevated BMI may be positively associated with risk of ER-PR- tumors among postmenopausal women who never used HRT. Furthermore, postmenopausal HRT users were at an increased risk of ER-PR- as well as ER+PR+ tumors, especially among leaner women. For hormone-receptor positive tumors, but not for hormone-receptor negative tumors, our study confirms an inverse association of risk with BMI among young women of premenopausal age. Our data provide evidence for a possible role of sex hormones in the etiology of hormone-receptor negative tumors.
PMCID: PMC3446339  PMID: 22583394
18.  Placental Weight and Risk of Invasive Epithelial Ovarian Cancer with an Early Age of Onset 
Epithelial ovarian cancer is associated with reproductive factors, but we lack knowledge if hormonal factors during pregnancy influence the mother’s risk. Because pregnancy hormones are primarily produced by the placenta, placental weight may be an indirect marker of hormone exposure during pregnancy.
In a nationwide Swedish cohort study, we included women with singleton births from 1982 to 1989. Women were followed for occurrence of invasive epithelial ovarian cancer, death, or emigration through 2004. Hazard ratios (HR) with 95% confidence intervals (95% CI) from Cox models were used to estimate associations between pregnancy exposures and epithelial ovarian cancer.
Among 395,171 women with information on placental weight in their first recorded birth, 316 women developed invasive epithelial ovarian cancer. Mean age at diagnosis was 44 years. Compared with women with a placental weight of 500 to 699 g, women with a high (≥700 g) placental weight had an increased riskof developing epithelial ovarian cancer (HR, 1.47; 95% CI, 1.14–1.90). Compared with women with term pregnancies (40–41 weeks), women with post-term (≥42 weeks) pregnancies had an increased risk of developing epithelial ovarian cancer (HR, 1.48; 95% CI, 1.00–2.19). These associations were slightly stronger when we included information about women’s overall first birth, and slightly weaker when we included information about last recorded birth or ever last birth from 1982 to 1989.
Because pregnancy hormone levels increase with placental weight, our study supports the hypothesis that hormone exposures during pregnancy influence the risk of invasive epithelial ovarian cancer among young women.
PMCID: PMC2643070  PMID: 18768502
19.  Alcohol consumption and breast cancer risk among postmenopausal women following the cessation of hormone therapy use: the California Teachers Study 
Alcohol consumption increases breast cancer risk, but its effect may be modified by hormone therapy (HT) use, such that exposure to both may be synergistic. Because many women stopped taking HT after mid-2002, it is important to quantify risks associated with alcohol consumption in the context of HT cessation, as these risks may be more relevant to cancer prevention efforts today.
Among 40,680 eligible postmenopausal California Teachers Study cohort participants, 660 were diagnosed with invasive breast cancer before 2010. Multivariate Cox proportional hazards regression models were used to estimate relative risks (RR) and 95% confidence intervals (CI).
Increased breast cancer risk associated with alcohol consumption was observed among postmenopausal women who were current HT users (RR=1.60, 95% CI: 1.13–2.26 and RR=2.11, 95% CI: 1.41–3.15 for <20 and ≥20 g/d of alcohol), with risks being similar by HT preparation. Alcohol did not increase risk among women who had stopped using HT within 3 years or 3–4 years before completing the follow-up questionnaire or in the more distant past. Results were similar for ER+ and ER+PR+ tumors; while power was limited, no increase in risk was observed for ER- tumors.
Following the cessation of HT use, alcohol consumption is not significantly associated with breast cancer risk, although a non-significant increased risk was observed among women who never used HT.
Our findings confirm that concurrent exposure to HT and alcohol has a substantial adverse impact on breast cancer risk. However, after HT cessation, this risk is reduced.
PMCID: PMC3721729  PMID: 22832206
breast cancer; alcohol; hormone therapy; cessation; epidemiology
20.  Body Size and Incident Colorectal Cancer: A Prospective Study of Older Women 
Obesity is a controversial risk factor for colorectal cancer (CRC) in older women. We evaluated associations between multiple body size parameters and incident CRC in the prospective, population-based Iowa Women's Health Study (IWHS). IWHS participants, ages 55–69 years, provided data regarding height; weight; weight at ages 50, 40, 30, 18 years; hip circumference; and waist circumference at baseline (1986). Derived variables included body mass index (BMI), waist-to-hip ratio (WHR) and “overweight years” (OWYs; conceptually similar to cigarette pack-years). Incident CRC cases (n=1464) were ascertained from the State Health Registry of Iowa, through 2005. Multivariable Cox regression models were fit to estimate body size-associated CRC risks. Among 36,941 women (619,961 person-years), baseline height, weight, BMI, hip circumference, waist circumference and WHR were all positively associated with incident CRC (p trend ≤ 0.003 for each). Baseline BMI yielded the highest CRC risk estimates (obese III versus normal, RR=1.56; 95% CI=1.10–2.22; p trend < 0.001) and was more closely associated with distal than proximal tumors (p trend < 0.001 vs. 0.06). Conversely, height was more closely associated with proximal than distal tumors (p trend < 0.001 vs. 0.04). Other body size parameters were less predictive of incident CRC. These data strongly support a positive association between increased body size and CRC risk among older women. Further investigation of when increased body size has the greatest effect on CRC risk (i.e., early adulthood versus later adulthood) might also be informative, particularly with respect to defining subsite-specific pathways of colorectal carcinogenesis.
PMCID: PMC3005991  PMID: 20719902
Colorectal Cancer; Body Size; Older Women; Cohort Study
21.  Maintaining a High Physical Activity Level Over 20 Years and Weight Gain 
JAMA : the journal of the American Medical Association  2010;304(23):10.1001/jama.2010.1843.
Data supporting physical activity guidelines to prevent long-term weight gain are sparse, particularly during the period when the highest risk of weight gain occurs.
To evaluate the relationship between habitual activity levels and changes in body mass index (BMI) and waist circumference over 20 years.
Design, Setting, and Participants
The Coronary Artery Risk Development in Young Adults (CARDIA) study is a prospective longitudinal study with 20 years of follow-up, 1985-86 to 2005-06. Habitual activity was defined as maintaining high, moderate, and low activity levels based on sex-specific tertiles of activity scores at baseline. Participants comprised a population-based multi-center cohort (Chicago, Illinois; Birmingham, Alabama; Minneapolis, Minnesota; and Oakland, California) of 3554 men and women aged 18 to 30 years at baseline.
Main Outcome Measures
Average annual changes in BMI and waist circumference
Over 20 years, maintaining high levels of activity was associated with smaller gains in BMI and waist circumference compared with low activity levels after adjustment for race, baseline BMI, age, education, cigarette smoking status, alcohol use, and energy intake. Men maintaining high activity gained 2.6 fewer kilograms (+ 0.15 BMI units per year; 95 % confidence interval [CI] 0.11-0.18 vs +0.20 in the lower activity group; 95% CI, 0.17-0.23) and women maintaining higher activity gained 6.1 fewer kilograms (+0.17 BMI units per year; 95 % CI, 0.12-0.21 vs. +0.30 in the lower activity group; 95 % CI, 0.25-0.34). Men maintaining high activity gained 3.1 fewer centimeters in waist circumference (+0.52 cm per year; 95 % CI, 0.43-0.61 cm vs 0.67 cm in the lower activity group; 95 % CI, 0.60-0.75) and women maintaining higher activity gained 3.8 fewer centimeters (+0.49 cm per year; 95 % CI, 0.39-0.58 vs 0.67 cm in the lower activity group; 95 % CI, 0.60-0.75).
Maintaining high activity levels through young adulthood may lessen weight gain as young adults transition to middle age, particularly in women.
PMCID: PMC3864556  PMID: 21156948
22.  Bilateral oophorectomy is not associated with increased mortality: the California Teachers Study 
Fertility and sterility  2011;97(1):111-117.
To investigate the effect of surgical menopause due to bilateral oophorectomy on mortality, in light of evidence that bilateral oophorectomy among premenopausal women rapidly reduces endogenous hormone levels thereby modifying risks of cardiovascular disease and breast cancer.
The California Teachers Study (CTS) is a prospective cohort study of 133,479 women initiated in 1995–1996 through a mailed, self-administered questionnaire. Relative risks (RR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression.
CTS participants who, at baseline, reported having surgical menopause due to bilateral oophorectomy (n=9,785), were compared to participants with natural menopause (n=32,219).
Main outcome measures
We investigated whether bilateral oophorectomy was associated with all-cause, cardiovascular, or cancer mortality, overall and by menopausal hormone therapy (HT) use status.
Among participants younger than 45 years of age at menopause, multivariable relative risks were 0.86 (95% CI, 0.74–1.00), 0.85 (95% CI, 0.66–1.11) and 0.91 (95% CI, 0.67–1.23) for all-cause mortality, cardiovascular mortality and cancer mortality, respectively. Among participants with an age at menopause of 45 years or later, multivariable relative risks were 0.87 (95% CI, 0.80–0.94), 0.83 (95% CI, 0.71–0.96) and 0.84 (95% CI, 0.72–0.98) for all-cause, cardiovascular and cancer mortality, respectively. The association between bilateral oophorectomy and mortality did not differ by baseline status of HT use.
Surgical menopause due to bilateral oophorectomy vs. natural menopause does not increase all-cause, cardiovascular, or cancer mortality.
PMCID: PMC3245786  PMID: 22088205
surgical menopause and mortality; bilateral oophorectomy; mortality; California Teachers Study
23.  Oral contraceptive use and reproductive factors and risk of ovarian cancer in the European Prospective Investigation into Cancer and Nutrition 
British Journal of Cancer  2011;105(9):1436-1442.
It is well established that parity and use of oral contraceptives reduce the risk of ovarian cancer, but the associations with other reproductive variables are less clear.
We examined the associations of oral contraceptive use and reproductive factors with ovarian cancer risk in the European Prospective Investigation into Cancer and Nutrition. Among 327 396 eligible women, 878 developed ovarian cancer over an average of 9 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models stratified by centre and age, and adjusted for smoking status, body mass index, unilateral ovariectomy, simple hysterectomy, menopausal hormone therapy, and mutually adjusted for age at menarche, age at menopause, number of full-term pregnancies and duration of oral contraceptive use.
Women who used oral contraceptives for 10 or more years had a significant 45% (HR, 0.55; 95% CI, 0.41–0.75) lower risk compared with users of 1 year or less (P-trend, <0.01). Compared with nulliparous women, parous women had a 29% (HR, 0.71; 95% CI, 0.59–0.87) lower risk, with an 8% reduction in risk for each additional pregnancy. A high age at menopause was associated with a higher risk of ovarian cancer (>52 vs ⩽45 years: HR, 1.46; 95% CI, 1.06–1.99; P-trend, 0.02). Age at menarche, age at first full-term pregnancy, incomplete pregnancies and breastfeeding were not associated with risk.
This study shows a strong protective association of oral contraceptives and parity with ovarian cancer risk, a higher risk with a late age at menopause, and no association with other reproductive factors.
PMCID: PMC3241548  PMID: 21915124
reproductive history; oral contraceptive use; ovarian cancer; cohort study
24.  Gender, anthropometric factors and risk of colorectal cancer with particular reference to tumour location and TNM stage: a cohort study 
It remains unclear whether the increased risk of colorectal cancer (CRC) associated with obesity differs by gender, distribution of fat, tumour location and clinical (TNM) stage. The primary aim of this study was to examine these associations in 584 incident colorectal cancer cases from a Swedish prospective population-based cohort including 28098 men and women.
Seven anthropometric factors; height, weight, bodyfat percentage, hip circumference, waist circumference, BMI and waist-hip ratio (WHR) were categorized into quartiles of baseline anthropometric measurements. Relative risks of CRC, total risk as well as risk of different TNM stages, and risk of tumours located to the colon or rectum, were calculated for all cases, women and men, respectively, using multivariate Cox regression models.
Obesity, as defined by all anthropometric variables, was significantly associated with an overall increased risk of CRC in both women and men. While none of the anthropometric measures was significantly associated with risk of tumour (T)-stage 1 and 2 tumours, all anthropometric variables were significantly associated with an increased risk of T-stage 3 and 4, in particular in men. In men, increasing quartiles of weight, hip, waist, BMI and WHR were significantly associated with an increased risk of lymph node positive (N1 and N2) disease, and risk of both non-metastatic (M0) and metastatic (M1) disease. In women, there were no or weak associations between obesity and risk of node-positive disease, but statistically significant associations between increased weight, bodyfat percentage, hip, BMI and M0 disease. Interestingly, there was an increased risk of colon but not rectal cancer in men, and rectal but not colon cancer in women, by increased measures of weight, hip-, waist circumference and bodyfat percentage.
This study is the first to show a relationship between obesity, measured as several different anthropometric factors, and an increased risk of colorectal cancer of more advanced clinical stage, in particular in men. These findings suggest that risk of CRC differs according to the method of characterising obesity, and also according to gender, location, and tumour stage.
PMCID: PMC3504577  PMID: 23072404
25.  Associations between Overall and Abdominal Obesity and Suicidal Ideation among US Adult Women 
Journal of Obesity  2012;2012:263142.
Obesity is associated with increased risks for mental disorders. This study examined associations of obesity indicators including body mass index (BMI), waist circumference, and waist-height ratio with suicidal ideation among U.S. women. We analyzed data from 3,732 nonpregnant women aged ≥20 years who participated in the 2005–2008 National Health and Nutrition Examination Survey. We used anthropometric measures of weight, height, and waist circumference to calculate BMI and waist-height ratio. Suicidal ideation was assessed using the Item 9 of the Patient Health Questionnaire-9. Odds ratios with 95% conference intervals were estimated using logistic regression analyses after controlling for potential confounders. The age-adjusted prevalence of suicidal ideation was 3.0%; the prevalence increased linearly across quartiles of BMI, waist circumference, and waist-height ratio (P for linear trend <0.01 for all). The positive associations of waist circumference and waist-height ratio with suicidal ideation remained significant (P < 0.05) after adjustment for sociodemographics, lifestyle-related behavioral factors, and having either chronic conditions or current depression. However, these associations were attenuated after both chronic conditions and depression were entered into the models. Thus, the previously reported association between obesity and suicidal ideation appears to be confounded by coexistence of chronic conditions and current depression among women of the United States.
PMCID: PMC3375088  PMID: 22720137

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