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Background: Obesity is a risk factor for postmenopausal breast cancer, but the role of the timing and amount of adult weight change in breast cancer risk is unclear., Methods: We prospectively examined the relations of adiposity and adult weight change to breast cancer risk among 99 039 postmenopausal women in the National Institutes of Health-AARP Diet and Health Study. Anthropometry was assessed by self-report in 1996. Through 2000, 2111 incident breast cancer cases were ascertained., Results: Current body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared), BMI at ages 50 and 35 years, and waist-hip ratio were associated with increased breast cancer risk, particularly in women not using menopausal hormone therapy (MHT). Weight gained between age 18 years and the current age, between ages 18 and 35 years, between ages 35 and 50 years, and between age 50 years and the current age was consistently associated with increased breast cancer risk in MHT nonusers (relative risk [RR], 2.15; 95% confidence interval [CI], 1.35-3.42 for a >/=50-kg weight gain between age 18 years and the current age vs stable weight) but not in current MHT users. Risk associated with adult weight change was stronger in women with later vs earlier age at menarche (RR, 4.20; 95% CI, 2.05-8.64 for >/=15 years vs RR, 1.51; 95% CI, 1.11-2.06 for 11-12 years; P = .007 for interaction). In MHT nonusers, the associations with current BMI and adult weight change were stronger for advanced disease than for nonadvanced disease (P = .009 [current BMI] and .21 [weight gain] for heterogeneity) and were stronger for hormone receptor-positive than hormone receptor-negative tumors (P < .001 for heterogeneity)., Conclusion: Weight gain throughout adulthood is associated with increased postmenopausal breast cancer risk in MHT nonusers.

Obesity and menopausal estrogen therapy are established risk factors for endometrial cancer. However, the joint effects of obesity and menopausal hormone therapy on endometrial cancer risk are incompletely understood. We addressed this issue in a cohort of 103,882 women ages 50 to 71 years at baseline in 1995 to 1996. During a median of 4.6 years, which contributed to a total of 455,304 person-years of follow-up through 2000, 677 cases of endometrial cancer were ascertained. Both baseline body mass index (BMI) and adult weight gain were associated with increased endometrial cancer risk. The multivariate relative risk (RR) comparing obese with normal weight women (BMI >30 versus <25 kg/m(2)) was 3.03 [95% confidence interval (95% CI), 2.50-3.68]. Compared with women with stable weight (gained or lost <5 kg) between age 18 and baseline, women who gained >or=20 kg had a RR of 2.75 (95% CI, 1.96-3.86). Menopausal hormone therapy significantly modified the relations of BMI (P(interaction) < 0.001) and adult weight gain (P(interaction) = 0.004) to endometrial cancer risk. Compared with normal weight, the RRs for obesity were 5.41 (95% CI, 4.01-7.29) among women who never used menopausal hormone therapy, 2.53 (95% CI, 1.21-5.30) among former menopausal hormone therapy users, and 1.44 (95% CI, 1.00-2.05) among current users. Compared with a stable weight between age 18 and baseline, the RRs for weight gain of >or=20 kg among never users and ever users of menopausal hormone therapy were 5.35 (95% CI, 3.01-9.52) and 1.43 (95% CI, 0.96-2.15), respectively. We conclude that both current adiposity and adult weight gain are associated with substantial increases in the risk of endometrial cancer, with relations particularly evident among never users of menopausal hormone therapy.

Background: Menopausal hormone therapy formulations for women without hysterectomy have included estrogen plus progestin for years, but endometrial cancer risks associated with the use of sequential and continuous estrogen-plus-progestin regimens remain unclear., Methods: The National Institutes of Health-AARP Diet and Health Study included 73,211 women who were ages 50 years to 71 years at baseline and who completed 2 questionnaires (1995-1996 and 1996-1997). Linkage to state cancer registries and mortality indices identified 433 incident endometrial cancers through 2000. Using proportional hazards regression, the authors estimated relative risks (RRs) and 95% confidence intervals (95% CIs) relative to never-use of hormone therapy., Results: In 51,312 women who never used hormones or only used estrogen-plus-progestin regimens at doses consistent with current practice, neither sequential estrogen plus progestin (daily estrogen plus progestin for 10-14 days per cycle: RR, 0.74; 95% CI, 0.39-1.40) nor continuous estrogen plus progestin (daily estrogen plus progestin for >/=20 days per cycle: RR, 0.80; 95% CI, 0.55-1.15) had any statistically significant association with endometrial cancer. Long durations (>/=5 years) of sequential regimen use (RR, 0.79; 95% CI, 0.38-1.66) and of continuous regimen use (RR, 0.85; 95% CI, 0.53-1.36) were not associated with endometrial cancer., Conclusions: Confirmation that these estrogen-plus-progestin regimens neither increase nor decrease the risk of endometrial cancer could influence menopausal symptom management for women who are considering estrogen-plus-progestin therapy., ((c) 2007 American Cancer Society.)

Background: Many factors contribute to mortality in older women, but their relative importance and independent contribution have been poorly characterized., Methods: From 1990 to 1992, we assessed demographics, lifestyle measures, prevalent disease, medication use, anthropometrics, vital signs, and physical function in 17 748 postmenopausal women. We used proportional hazards modeling to evaluate their association with mortality., Results: During 9 years of follow-up, 1886 women (10.6%) died. The relative hazard (RH) of death was approximately 1.5 (95% confidence interval [CI], 1.5-1.6) per 5 years of age, 1.4 (95% CI, 1.2-1.6) for a history of heart disease, and 1.9 (95% CI, 1.6-2.3) for a history of breast cancer. Modifiable risk factors associated with mortality included smoking (RH, 3.7 [95% CI, 3.1-4.5] for current smokers with a > or =50 pack-year history) and systolic blood pressure (RH, 1.3 [95% CI, 1.1-1.5], fifth vs first quintile). Elevated waist-hip ratio was associated with higher mortality (RH, 1.3 [95% CI, 1.1-1.5], fifth vs first quintile), but obesity was associated with lower mortality (RH, 0.7 [95% CI, 0.6-0.9] for body mass index [calculated as weight in kilograms divided by the square of height in meters] of >35.0 vs 18.5-25.0). Poor results on the timed Up and Go Test, a measure of physical function, were also strongly associated with mortality (RH, 1.7 [95% CI, 1.4-2.0], fifth vs first quintile)., Conclusions: Simple measures are sufficient to stratify postmenopausal women into groups at high and low risk of dying. Smoking, central obesity, blood pressure, and physical function are potentially modifiable risk factors, although clinical trials are required to demonstrate that change in these factors affects mortality.

Purpose: Reported associations between ovarian cancer and body size are inconsistent. We assessed ovarian cancer and anthropometry in the Breast Cancer Detection Demonstration Project Follow-Up Study., Methods: The 46,026 participants completed a baseline interview and mailed questionnaires between 1979 and 1998. By using multiple sources, we identified 346 incident ovarian cancers during follow-up. We calculated rate ratios (RRs) and 95% confidence intervals (CIs) to estimate relative risks for developing ovarian cancer associated with height and weight (measured 1973 to 1980) and self-reported current and usual adult weight (collected during follow-up)., Results: Neither taller height (> or =66 versus <62 inches; RR, 0.90; 95% CI, 0.64-1.26) nor greater weight (> or =161 versus < or =120 lbs; RR, 1.09; 95% CI, 0.77-1.55) was associated with ovarian cancer. Compared with normal weight (body mass index [BMI], 18.5 to 24.9 kg/m(2)), overweight (BMI, 25 to 29.9 kg/m(2); RR, 1.00; 95% CI, 0.78-1.29) and obesity (BMI, 30 to 34.9 kg/m(2); RR, 0.94; 95% CI, 0.59-1.48) were not associated with ovarian cancer. Severe obesity (BMI > or = 35 kg/m(2)) produced a nonsignificantly elevated RR (1.55; 95% CI, 0.84-2.84). Associations with histologic types and statistical interactions with menopausal status and hormone therapy use were null., Conclusions: Based on height and weight measured before baseline, overweight and obesity were not significantly associated with ovarian cancer in this cohort.

Sex is a consistent predictor of bladder cancer: men experience 2-4-fold higher age-adjusted rates than women in the U.S. and Europe. The objective of this study was to examine whether hormone-related factors are associated with bladder cancer in women. We examined parity, age at menarche, age at first birth, age at menopause, oral contraceptive use and menopausal hormone therapy (HT) use and bladder cancer risk in the Breast Cancer Detection Demonstration Project Follow-Up Study. Endpoint and exposure information was collected on 54,308 women, using annual telephone interviews (1980-86) and 3 mailed, self-administered questionnaires (1987-98). During an average follow-up time of 15.3 years, 167 cases of bladder cancer were identified. Univariate and adjusted rate ratios (RRs) were estimated using Poisson regression. Parity, age at menarche, age at first birth, age at menopause, and oral contraceptive use were not associated with bladder cancer risk. The majority of menopausal women who took HT used estrogen therapy (ET). Postmenopausal women with less than 4 years, 4-9 years, 10-19 years and 20 or more years of ET use had RRs of 1.55 (95% CI = 0.96-2.51), 1.00 (95% CI = 0.49-2.04), 1.23 (95% CI = 0.62-2.43) and 0.57 (95% CI = 0.14-2.34), respectively, compared with nonusers (p = 0.50). Findings from this study are not consistent with the hypothesis that hormone-related factors in women are associated with bladder cancer.

Objective: Difficulties in detecting cervical adenocarcinoma early are well known. We report a detailed pathology review of cervical adenocarcinoma subtypes, comparing growth patterns and appearance of non-neoplastic epithelium to inform possible clues for disease progression and early detection., Methods: This analysis includes 154 women aged 18-69 years and diagnosed with incident in situ or invasive adenocarcinoma (AC), adenosquamous (AS), or other rare cervical glandular tumors from 1992-1996 in six U.S. medical centers. A pathology review panel evaluated histological features from original diagnostic slides., Results: Higher tumor grade (P < 0.001) and vascular invasion (P = 0.002) were more common in AS compared to AC. Adenocarcinoma in situ (AIS) was also more common among AC than AS (P = 0.002). Among AC with cervical intraepithelial carcinoma (CIN), AIS and cribriform patterns were more common than AC without CIN (P = 0.01). Further, non-endometrioid AC had higher tumor grade (P = 0.01) and stromal responses (P = 0.02) than endometrioid AC. Finally, although microglandular hyperplasia is historically thought to be related to oral contraceptive (OC) use, our data do not support this notion., Conclusion(s): AS appears to be either diagnosed later or histologically more aggressive than AC, and among AC subtypes, there are distinct histologic characteristics. Further research is needed to identify precursor lesions for early detection of AC and particularly for AS where AIS may not be a common precursor.

Background: Recent studies offer conflicting data on risks of ovarian cancer in users of menopausal hormone therapy. Some findings of increased risks associated with unopposed estrogen use are based on older studies of women with intact uteri, and small sample size and incomplete exposure information have limited the data on estrogen plus progestin associations., Methods: The National Institutes of Health-AARP Diet and Health Study Cohort included 97,638 women aged 50-71 years at baseline who completed two questionnaires (1995-1996 and 1996-1997). We identified 214 incident ovarian cancers among these women through the year 2000 using data from state cancer registries and mortality indexes. We estimated relative risks (RRs) of ovarian cancer for detailed hormone therapy exposures using multivariable proportional hazards regression models. All statistical tests were two-sided., Results: Use of unopposed estrogen for fewer than 10 years was not associated with ovarian cancer. Compared with use of no hormone therapy, use of unopposed estrogen for 10 or more years was statistically significantly associated with ovarian cancer among all women (RR = 1.89, 95% confidence interval [CI] = 1.22 to 2.95; P = .004; 56 versus 72 ovarian cancers per 100,000 person-years, respectively) and, albeit not statistically significantly, among women with hysterectomy (n = 19,359, RR = 1.70, 95% CI = 0.87 to 3.31; P = .06). Among the 73,483 women with intact uteri, 51,698 had used no hormone therapy or only estrogen plus progestin. Compared with no hormone therapy use, 5 or more years of use of sequential (progestin for < 15 days per cycle; RR = 3.09, 95% CI = 1.68 to 5.68; P < .001; 49 versus 108 per 100,000 person-years) or continuous (progestin for > or = 15 days per cycle; RR = 1.82, 95% CI = 1.03 to 3.23; P = .02; 49 versus 66 per 100,000 person-years) estrogen plus progestin regimens were statistically significantly associated with ovarian cancer., Conclusions: Long durations of use of unopposed estrogen and of estrogen plus progestin, especially sequential regimens, are associated with increased ovarian cancer risk. These data expand the range of possible risks associated with menopausal hormone therapy.

Background: A family history of breast cancer has been associated with increased ovarian cancer risk. However, few studies have assessed risk according to characteristics that suggest an inherited cancer susceptibility disorder, such as earlier-than-usual age at cancer diagnosis, family members with double primary cancers of different types, multiple relatives with cancer, and cancer in both members of paired organs., Methods: Ovarian cancer risk was assessed according to a detailed breast cancer family history among 49,975 participants in the Breast Cancer Detection Demonstration Project Breast Cancer Defection Demenstration Project (BCDDP) Follow-up Study (1979-1998). In all, 362 incident ovarian cancers were identified during follow-up and rate ratios (RRs) were calculated by Poisson regression. RESULTS.: Breast cancer in a first- or second-degree relative was associated with increased risk of ovarian cancer (RR = 1.4; 95% confidence interval [CI] = 1.1-1.7). Having 2 or more affected first-degree relatives was associated with increased risk (RR = 1.8; 95% CI = 1.1-2.8), especially for women diagnosed with ovarian cancer before age 60 (RR = 4.2; 95% CI = 1.9-9.2) or with a personal history of breast cancer (RR = 3.7; 95% CI 1.8-7.7). Risk was also particularly high for women with 2 or more first-degree relatives with breast cancer and at least 1 affected relative diagnosed before age 50 (RR = 2.6; 95% CI = 1.4-4.8) or with bilateral breast cancer (RR = 4.2; 95% CI = 1.7-10)., Conclusions: A detailed breast cancer family history as well as an individual's age and personal history of breast cancer are useful for identifying women at elevated genetic risk of ovarian cancer.

Clinical studies have reported associations between ovarian stromal hyperplasia and the diagnosis of hormonally related tumors such as endometrial cancer. To assess the hypothesis that characteristics of benign ovaries among postmenopausal women are related to risk for breast, endometrial, and colon cancer, we analyzed systematically collected transvaginal ultrasound data for participants enrolled in the screening arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Among women without cancer, median ovarian volume declined with age from 1.25 cm3 for women between ages 55 and 59 years to 1.0 cm3 for those between ages 65 and 69 years. African American and Caucasian women had larger median ovarian volumes than Asians. Larger ovarian volume was also associated with the highest quartiles of height and weight and ever having smoked. After adjusting for race, age, parity, body mass, smoking, and hormone use, women with median ovarian volumes >or=3.0 cm3 were at increased risk for breast cancer [odds ratio (OR), 1.42; 95% confidence interval (95% CI), 1.11-1.70], endometrial cancer (OR, 1.97; 95% CI, 1.12-3.48), and colon cancer (OR, 2.00; 95% CI, 1.25-3.21). Significant trends of risk with increasing volume were found only for breast and endometrial cancers. We conclude that large ovaries among postmenopausal women may represent a marker of risk for hormonally related tumors. Confirmation of these findings in future studies, including analyses of serum hormone levels and tissues, may provide insights into hormonal carcinogenesis among older women.

Physical activity has frequently been reported to decrease the risk of colon cancer in men, but data on the relation of physical activity to colon cancer risk in women have generally been less consistent. To further investigate the relationship of physical activity with colon cancer risk in women, we studied a cohort of 31,783 US women participating in the Breast Cancer Detection Demonstration Project Follow-up Study. Information on daily physical activity over the past year was ascertained using a self-administered questionnaire at study baseline. The Cox proportional hazards model was used to estimate relative risks (RRs) relating physical activity to the risk of incident colon cancer. During 270,325 person-years of follow-up, 243 colon cancer cases were identified. No association was observed between physical activity and the subsequent risk of colon cancer. The multivariable RRs of colon cancer across increasing quintiles of total physical activity were 1.0, 1.45, 1.16, 1.27 and 1.15 (95% CI: 0.76, 1.75; p(trend) = 0.77). The multivariable RRs comparing women at the extremes of moderate and vigorous physical activity, respectively, were 1.07 (95% CI: 0.70, 1.62) and 1.10 (95% CI: 0.78, 1.55). The relationship between physical activity and colon cancer risk did not vary by anatomic subsite or across subgroups defined by age, body mass, dietary fiber intake, menopausal status, menopausal hormone use or aspirin use. The results of this large prospective cohort study among women do not support the hypothesis that physical activity is related to a lower incidence of colon cancer., (2006 Wiley-Liss, Inc.)

Energy restriction remains one of the most effective ways known to prevent breast cancer in animal models. However, energy intake has not been consistently associated with risk of breast cancer in humans. In a prospective study, we assessed whether energy intake, body size, and physical activity each independently influence breast cancer risk in postmenopausal women and estimated the joint effect of combinations of these individual factors. As part of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, 38,660 women, ages 55 to 74 years and recruited from 10 centers in the United States during 1993 to 2001, were randomized to the screening arm of the trial. At baseline, the women completed a self-administered questionnaire, including a food frequency questionnaire. During follow-up from 1993 to 2003, 764 incident breast cancer cases were ascertained. Women in the highest quartile of energy intake (> or = 2,084 kcal/d) compared with those in the lowest quartile (<1,316 kcal/d) had a significantly increased risk for breast cancer [multivariate relative risk (RR), 1.25; 95% confidence interval (95% CI), 1.02-1.53; P(trend continuous) = 0.03]. Current body mass index (BMI) was also positively and significantly associated with risk (multivariate RR comparing >30 kg/m2 with <22.5 kg/m2, 1.35; 95% CI, 1.06-1.70; P(trend) = 0.01). Women with > or = 4 hours/wk of vigorous recreational physical activity had a significantly reduced risk of breast cancer compared with those who reported no recreational physical activity (multivariate RR, 0.78; 95% CI, 0.60-0.99; P(trend) = 0.15). None of these associations with individual energy balance measures was substantially confounded by the other two measures. When we estimated the joint effect of all three variables, women with the most unfavorable energy balance (the highest energy intake, highest BMI, and least physical activity) had twice the risk (RR, 2.10; 95% CI, 1.27-3.45) of women with the most favorable energy balance (the lowest energy intake, lowest BMI, and most physical activity). Although our estimates of absolute energy intake, based on a food frequency questionnaire, are imperfect, these results suggest that energy intake, in addition to BMI and physical activity may be independently associated with breast cancer risk. In addition, these three aspects of energy balance may act jointly in determining breast cancer risk.

Background: Dairy foods and their constituents (lactose and calcium) have been hypothesized to promote ovarian carcinogenesis. Although case-control studies have reported conflicting results for dairy foods and lactose, several cohort studies have shown positive associations between skim milk, lactose, and ovarian cancer., Methods: A pooled analysis of the primary data from 12 prospective cohort studies was conducted. The study population consisted of 553,217 women among whom 2,132 epithelial ovarian cases were identified. Study-specific relative risks and 95% confidence intervals were calculated by Cox proportional hazards models and then pooled by a random-effects model., Results: No statistically significant associations were observed between intakes of milk, cheese, yogurt, ice cream, and dietary and total calcium intake and risk of ovarian cancer. Higher lactose intakes comparing > or = 30 versus <10 g/d were associated with a statistically significant higher risk of ovarian cancer, although the trend was not statistically significant (pooled multivariate relative risk, 1.19; 95% confidence interval, 1.01-1.40; P(trend) = 0.19). Associations for endometrioid, mucinous, and serous ovarian cancer were similar to the overall findings., Discussion: Overall, no associations were observed for intakes of specific dairy foods or calcium and ovarian cancer risk. A modest elevation in the risk of ovarian cancer was seen for lactose intake at the level that was equivalent to three or more servings of milk per day. Because a new dietary guideline recommends two to three servings of dairy products per day, the relation between dairy product consumption and ovarian cancer risk at these consumption levels deserves further examination.

In the United States, endometrial carcinoma incidence rates, uncorrected for hysterectomy prevalence, are higher among white women than black women. We estimated corrected endometrial carcinoma rates by racial/ethnic groups and age (30-74 years) for 1992-2000 using data from the Surveillance, Epidemiology, and End Results program and the Behavioral Risk Factor Surveillance Survey. Hysterectomy prevalence was higher among black women than among Hispanic and white non-Hispanic women. Correcting for hysterectomy prevalence increased age-adjusted endometrial carcinoma rates per 10(5) woman-years from 29.2 to 48.7 (66.8% increase) overall, from 14.6 to 28.5 (95.3% increase) in blacks, from 18.8 to 29.6 (57.6% increase) in Hispanics, and from 33.2 to 54.9 (65.1%) in white non-Hispanics. This correction reduced the rate ratio for white non-Hispanics compared with blacks from 2.27 to 1.93. Among blacks but not Hispanics or white non-Hispanics, the endometrial carcinoma risk factors of obesity and diabetes were more prevalent among hysterectomized than nonhysterectomized women. Failure to correct for hysterectomy prevalence may lead to underestimates of endometrial carcinoma risk, especially among blacks. The high prevalence of hysterectomy among blacks with strong endometrial cancer risk factors may partly account for lower cancer rates in this group.

Background: Because unopposed estrogen substantially increases endometrial carcinoma risk, estrogen plus progestin is one menopausal hormone therapy formulation for women who have not had a hysterectomy. However, endometrial carcinoma risks among estrogen plus progestin users and among former unopposed estrogen users are not firmly established., Methods: We evaluated endometrial carcinoma risks associated with estrogen plus progestin and unopposed estrogen therapies in 30,379 postmenopausal Breast Cancer Detection Demonstration Project follow-up study participants. We ascertained hormone therapy use and other risk factors during telephone interviews and mailed questionnaires between 1979 and 1998. We identified 541 endometrial carcinomas via self-report, medical records, the National Death Index, and state cancer registries. Poisson regression generated time-dependent rate ratios (RR) and 95% confidence intervals (95% CI)., Results: Endometrial carcinoma was significantly associated with estrogen plus progestin only use (n = 68 cancers; RR, 2.6; 95% CI, 1.9-3.5), including both sequential (progestin <15 days per cycle; n = 32 cancers; RR, 3.0; 95% CI, 2.0-4.6) and continuous (progestin at least 15 days per cycle; n = 15 cancers; RR, 2.3; 95% CI, 1.3-4.0) regimens. The RR increased by 0.38 (95% CI, 0.20-0.64) per year of estrogen plus progestin use, and RRs increased with increasing duration of use for both regimens. The strong association with unopposed estrogen use declined after cessation but remained significantly elevated > or =10 years after last use (RR, 1.5; 95% CI, 1.0-2.1)., Conclusions: Both estrogen plus progestin regimens significantly increased endometrial carcinoma risk in this study. Risks among unopposed estrogen users remained elevated long after last use. The prospect that all estrogen plus progestin regimens increase endometrial carcinoma risk deserves continued research.

Background: We have previously reported on the utility of the Recommended Foods Score (RFS), a measure of overall diet quality, in detecting associations between diet and mortality in a cohort of older women. Using additional follow-up, we have now extended our analysis to detailed studies of associations between RFS and the mortality and incidence from common cancers., Methods: The RFS, the sum of 23 recommended food items consumed at least weekly, was computed from a 62-item food frequency questionnaire completed at baseline by 42 254 women with a mean age of 61 years. Multivariate adjusted relative risk (RR) of cancer mortality and incidence of the cancers for which we were able to obtain data in relation to quartiles of RFS were examined using proportional hazards regression analyses after a median follow-up period of 9.5 years., Results: We observed that RFS was inversely associated with total mortality (RR = 0.8; P < 0.001) cancer mortality (RR = 0.74; P < 0.001) as well as mortality from cancers of the breast (RR = 0.75; P < 0.06), colon/rectum (RR = 0.49; P < 0.01) and lung (RR = 0.54; P < 0.001). The risk of incident lung cancer (RR = 0.62; P < 0.001) was reduced in women in the highest vs the lowest quartile of RFS; for incident cancers of the breast, colorectum, endometrium, ovaries, and bladder, there was no RFS association., Conclusion: A dietary pattern reflecting a higher RFS was associated with decreased overall mortality in women, specifically cancers of the lung, colon/rectum, and to a lesser extent breast. Incidence was only decreased for lung cancers. These observations are consistent with the hypothesis that a high RFS dietary pattern, or associated lifestyle factors, might affect cancer progression and survival.

We investigated the association between calcium intake and colorectal cancer in a prospective cohort of 45,354 women without a history of colorectal cancer who successfully completed a 62-item National Cancer Institute/Block food-frequency questionnaire. Women were followed for an average of 8.5 years, during which time 482 subjects developed colorectal cancer. We used Cox proportional hazards models, with age as the underlying time metric, to estimate risk of colorectal cancer. Cut points between quintiles of energy-adjusted dietary calcium were 412, 529, 656, and 831 mg/day. We created categories for calcium from supplements as follows: 0 mg/day (n = 25,441), 0 to 400 mg/day (n = 9,452), 401 to 800 mg/day (n = 4,176), and >800 mg/day (n =6,285). Risk ratios and confidence intervals (95% CI) for increasing quintiles of dietary calcium relative to the lowest quintile were 0.79 (0.60-1.04), 0.77 (0.59-1.02), 0.78 (0.60-1.03), and 0.74 (0.56-0.98), P(trend) = 0.05. For increasing categories of calcium from supplements, the risk ratios (and 95% CI) relative to no supplement use were 1.08 (0.87-1.34), 0.96 (0.70-1.32), and 0.76 (0.56-1.02), P(trend) = 0.09. Simultaneously high consumption of calcium from diet and calcium from supplements resulted in even further risk reduction, RR = 0.54 (95% CI, 0.37-0.79) compared with low consumption of both sources of calcium. These data indicate that a difference of < 400 to > 800 mg of calcium per day was associated with an approximately 25% reduction in risk of colorectal cancer, and this reduction in risk occurred regardless of the source of the calcium (i.e., diet or supplements).

Increased physical activity may lower the risk of ovarian cancer by reducing the frequency of ovulation, decreasing body fat, or diminishing chronic inflammation. Previous epidemiological studies examining the association between physical activity and risk of ovarian cancer have been inconsistent. We investigated the association of physical activity with ovarian cancer in a prospective cohort of 27,365 individuals from the Breast Cancer Detection Demonstration Project. During 227,045 person-years of follow-up, 121 cases of ovarian cancer were ascertained. Usual physical activity during the past year was assessed by a self-administered questionnaire. After adjusting for potential risk factors for ovarian cancer, the relative risks (95% confidence intervals) across increasing quintiles of total physical activity were 1.0, 0.73 (0.43-1.25), 0.84 (0.50-1.40), 0.56 (0.31-1.00), and 0.70 (0.41-1.21), respectively (P for trend = 0.13). In this prospective cohort study among U.S. women, we found no overall significant association between physical activity and risk of ovarian cancer, although the results are suggestive of an inverse association.

Objective: To assess whether circulating insulin-like growth factor-1 (IGF-1), IGF-2, insulin-like growth factor-binding protein-1 (IGFBP-1), or IGFBP-3 were associated with endometrial cancer in postmenopausal women., Study Design: Between 1987 and 1990, we conducted a case-control study of 405 women with endometrial cancer and 297 matched population-based controls. This analysis included 174 postmenopausal cases and 136 controls., Results: In logistic regression models adjusted for potential confounders, higher IGF-1 levels were not positively associated with endometrial cancer: odds ratio (OR) for the highest tertile versus the lowest tertile = 0.63, 95% confidence interval (CI) = 0.30-1.32. Endometrial cancer was inversely associated with IGF-2 (OR for the highest tertile = 0.35, 95% CI = 0.18-0.69) and IGFBP-3 (OR for the highest tertile = 0.40, 95% CI = 0.21-0.77), and not associated with IGFBP-1., Conclusion: Serum IGF-1, IGF-2, and IGFBP-3, but not IGFBP-1, were inversely associated with endometrial cancer in postmenopausal women. These associations and the potential role of the IGF system in endometrial proliferation and carcinogenesis warrant further research.

Background: Although cervical carcinoma incidence and mortality rates have declined in the U.S. greatly since the introduction of the Papanicolaou smear, this decline has not been uniform for all histologic subtypes. Therefore, the authors assessed the differential incidence rates of squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the cervix by race and disease stage for the past 25 years., Methods: Data from nine population-based cancer registries participating in the U.S. Surveillance, Epidemiology, and End Results (SEER) Program were used to compute incidence rates for cervical carcinoma diagnosed during 1976-2000 by histologic subtype (SCC and AC), race (black and white), age, and disease stage (in situ, localized, regional, or distant)., Results: In black women and white women, the overall incidence of invasive SCC declined over time, and the majority of tumors that are detected currently are in situ and localized carcinomas in young women. The incidence of in situ SCC increased sharply in the early 1990s. AC in situ (AIS) incidence rates increased, especially among young women. In black women, invasive AC incidence rose linearly with age., Conclusions: Changes in screening, endocervical sampling, nomenclature, and improvements in treatment likely explain the increased in situ cervical SCC incidence in white women and black women. Increasing AIS incidence over the past 20 years in white women has not yet translated into a decrease in invasive AC incidence. Etiologic factors may explain the rising invasive cervical AC incidence in young white women; rising cervical AC incidence with age in black women may reflect either lack of effective screening or a differential disease etiology., (Copyright 2004 American Cancer Society.)

Inflammation and gonadotropins are hypothesized to influence ovarian carcinogenesis. In a prospective study, we evaluated ovarian cancer risk associated with self-reported use of medications that influence inflammation or gonadotropin levels. The Breast Cancer Detection Demonstration Project Follow-Up Study enrolled 61,431 women in 1979 and used telephone interviews and 3 mailed questionnaires through 1998 to update risk factor information and identify incident ovarian cancers. The 1992-95 questionnaire ascertained medication use, including duration and frequency of use for aspirin, acetaminophen, other nonsteroidal anti-inflammatory drugs (NSAIDs), tranquilizers and histamine-receptor antagonists. A Poisson regression analysis generated rate ratios (RRs) and 95% confidence intervals (CIs) for the 31,364 women who were at risk of ovarian cancer and responded to the questionnaire that queried regular medication use. One hundred sixteen women developed ovarian cancer during follow-up. None of the anti-inflammatory medications was associated with ovarian cancer, but the RR for more than 1 aspirin per day for 1 year or longer was 0.56 (95% CI 0.20-1.5) and the RR for more than 5 years of regular "other NSAID" use was 2.0 (95% CI 0.95-4.2). Regular tranquilizer use was not associated with ovarian cancer, but histamine-receptor antagonists used regularly for more than 5 years (RR = 3.6, 95% CI 1.4-9.1) or more than once daily (RR = 3.1, 95% CI 1.5-6.5) appeared to increase risk. In our study, neither anti-inflammatory medications nor anti-psychotic medications were associated with ovarian cancer. Potential associations with histamine-receptor antagonists may warrant further study., (Copyright 2003 Wiley-Liss, Inc.)

Background: Hormonal factors may play a more prominent role in cervical adenocarcinoma than squamous cell carcinoma. The authors evaluated whether obesity, which can influence hormone levels, was associated with adenocarcinoma and squamous cell carcinoma., Methods: This case-control study included 124 patients with adenocarcinoma, 139 matched patients with squamous cell carcinoma, and 307 matched community control participants. All participants completed interviews and provided cervicovaginal samples for human papillomavirus (HPV) testing. Polytomous logistic regression-generated odds ratios (ORs) and 95% confidence intervals (95% CIs) for self-reported height and weight, body mass index (BMI; kg/m(2)), and measured waist-to-hip ratio (WHR) for both histologic types were adjusted and stratified for HPV and other confounders., Results: Height, weight, BMI, and WHR were positively associated with adenocarcinoma. BMI >or= 30 kg/m(2) (vs. BMI < 25 kg/m(2); OR, 2.1 and 95% CI, 1.1-3.8) and WHR in the highest tertile (vs. the lowest tertile; OR, 1.8 and 95% CI, 0.97-3.3) were associated with adenocarcinoma. Neither height nor weight was found to be associated with squamous cell carcinoma, and associations for BMI >or= 30 kg/m(2) (OR, 1.6) and WHR in the highest tertile (OR, 1.6) were weaker and were not statistically significant. Analyses using only HPV positive controls showed similar associations. The data were adjusted for and stratified by screening, but higher BMI and WHR were associated with higher disease stage at diagnosis, even among recently and frequently screened patients with adenocarcinoma. Thus, residual confounding by screening could not be excluded as an explanation for the associations., Conclusions: Obesity and body fat distribution were associated more strongly with adenocarcinoma than with squamous cell carcinoma. Although questions about screening remain, obesity may have a particular influence on the risk of glandular cervical carcinoma.

Objective: To estimate the prevalence, incidence, survival, and disease characteristics of systemic sclerosis (SSc) in the Detroit tricounty area., Methods: A census of SSc cases for the period 1989-1991 was conducted in the Detroit area, using multiple sources for case identification. Diagnoses were verified by medical record review. Capture-recapture analysis was used to estimate the total SSc population. Cases of localized scleroderma (morphea and linear disease) were excluded., Results: Based on 706 verified cases of SSc, prevalence was initially estimated to be 242.0 cases per million adults (95% confidence interval [95% CI] 213-274), with an annual incidence of 19.3 new cases per million adults per year (95% CI 12.4-30.2). Capture-recapture analysis, based on the degree of overlap of verified cases among multiple sources, resulted in a revised prevalence estimate of 276 cases per million adults (95% CI 245-310). Sex- and race-specific prevalence estimates were significantly higher for women than for men, and for blacks than for whites. The average age at diagnosis was significantly younger for blacks than for whites. Compared with white patients, black patients were almost twice as likely to have diffuse disease (prevalence proportion ratio 1.86, 95% CI 1.48-2.35). Median survival was approximately 11 years. Factors negatively affecting survival included male sex (hazard ratio 1.81, 95% CI 1.29-2.55) and older age at diagnosis (hazard ratio 1.04, 95% CI 1.03-1.05)., Conclusion: This study establishes baseline estimates of SSc occurrence and characteristics in a large US cohort consisting primarily of black adults and white adults. These data should facilitate research regarding the role of geographic, ethnic, racial, and environmental factors for this disease in comparison populations.

Objective: To examine the physical activity and endometrial cancer relationship in a prospective study of US women enrolled in the Breast Cancer Detection Demonstration Project (BCDDP) Follow-up Study., Methods: We assessed past-year physical activity of all types in 23,369 women who returned the baseline questionnaire (1987-1989) and had no prior hysterectomy and/or endometrial cancer. Cox proportional hazards models were used to estimate age, education, and parity-adjusted rate ratios (RR) and 95% confidence intervals (CI) for the 253 confirmed endometrial cancer cases identified during an average 8.2 years of follow-up (ending 1995-1998)., Results: There were no dose-response relationships with either total or vigorous physical activity; however, compared to the lowest total activity quartile, the higher four quartiles had a non-significantly lower risk (RR = 0.8, CI = 0.6-1.0). The association with moderate activity varied with follow-up time: RRs (CI) for a 1 h increase in daily moderate activity within 2-year intervals of follow-up (< or = 2, 2.1-4.9, 5.0-8.0, > 8 years) were 1.1 (1.0, 1.2), 1.0 (0.9, 1.1), 1.0 (0.9, 1.1), 1.0 (0.9, 1.1), and 0.8 (0.7, 1.0), respectively., Conclusion: These data suggest that recent physical activity is not strongly related to the risk of endometrial cancer, and that prolonged exposure and longer follow-up may be necessary.

The authors investigated the association of intakes of meat and fat with colorectal cancer in a prospective cohort of women in the United States. Between 1987 and 1989, 45,496 women completed a 62-item National Cancer Institute/Block food frequency questionnaire, and during 386,716 person-years of follow-up, there were 487 incident cases of colorectal cancer. The authors used Cox proportional hazards regression to estimate relative risks and 95% confidence intervals for total meat, red meat, white meat, processed meat, and well-done meat intakes, as well as for total fat, saturated fat, and unsaturated fat. Relative risks for increasing quintiles of total meat and red meat consumption indicated no association with colorectal cancer (relative risk for high compared with low quintile = 1.10, 95% confidence interval: 0.83, 1.45) for red meat. For total fat, there was also no association with increasing quintiles of consumption (relative risk for high compared with low quintile = 1.14, 95% confidence interval: 0.86, 1.53). Additionally, none of the other subtypes of either meat or fat showed any association with colorectal cancer. This study provided no evidence of an association between either meat or fat (or any of their subtypes) and colorectal cancer incidence, but the authors cannot rule out the possibility of a modest association.

Background: The hypothesis that increased intake of dietary fibre lowers the risk of colorectal cancer (CRC) has recently been weakened by results from cohort and intervention studies that did not detect such an association. We investigated the association between dietary fibre intake and risk of CRC in a cohort of women that prospectively answered a food frequency questionnaire (FFQ)., Methods: We studied 45 491 women in the Breast Cancer Detection Demonstration Project (BCDDP) follow-up cohort. A 62-item FFQ was administered from 1987 and 1989 to assess dietary intake. Participants received follow-up questionnaires (in 1992-1995 and 1995-1998) on which they reported incident cancers. Cases were also identified through searches of the National Death Index and state cancer registries. Cox proportional hazard regression was used to generate risk ratios and 95% CI for quintiles of total fibre intake and fibre subtypes., Results: During a mean follow-up time of 8.5 years we identified 487 colorectal cancer cases. The 10th and 90th percentiles of dietary fibre intake were 5.4 g and 18.2 g respectively. For total fibre we observed no association with colorectal cancer (fifth versus first quintile, RR = 0.94, 95% CI: 0.71-1.23). Analyses by subgroup of fibre and by anatomical subsite did not reveal any stronger inverse associations., Conclusions: Within a cohort of older women characterized by a relatively low fibre intake, there was little evidence that dietary fibre intake lowers the risk of colorectal cancer.

Exposure to solvents has been reported to increase the risk of scleroderma. The authors investigated the relation between exposures to solvents in occupational and hobby settings and the development of scleroderma among women in a case-control study with population-based controls in Michigan (1980-1991) and Ohio (1980-1992). A total of 660 cases and 2,227 frequency-matched controls were interviewed by telephone. Diagnoses of scleroderma were verified by medical records review. Paint thinners and removers were significantly associated with scleroderma both by self-report (odds ratio (OR) = 1.9, 95% confidence interval (CI): 1.4, 2.6) and after expert review (OR = 2.0, 95% CI: 1.5, 2.6). Other petroleum distillates (gasoline and mineral spirits) were not significantly associated with scleroderma after controlling for other correlated exposures in multivariable analyses. Trichloroethylene was associated with scleroderma both by self-report (OR = 2.0, 95% CI: 0.8, 4.8) and after expert review (OR = 1.9, 95% CI: 0.6, 6.6), but not significantly. Analyses by duration of exposure found that risk increased with the duration of use of any of the solvents (OR = 1.01/year of exposure, 95% CI: 1.01, 1.02), but there was no evidence of increasing risk with increasing duration of exposure for any specific solvent studied. In summary, exposures to paint thinners and removers were associated with scleroderma in women but showed no evidence of increasing risk with increasing duration. Exposures to other specific chlorinated and nonchlorinated hydrocarbon solvents were not clearly associated with scleroderma.

Objective: Although human papillomavirus causes essentially all cervical carcinoma, cofactors may differ by cancer histologic type. We examined human papillomavirus genotypes and sexual and reproductive risk factors for cervical adenocarcinoma and squamous cell carcinoma., Study Design: One hundred twenty-four women with adenocarcinoma, 139 women with squamous cell carcinoma, and 307 control subjects participated in this case-control study. Logistic regression analyses were performed to calculate odds ratios and CIs., Results: Human papillomavirus 18 was associated most strongly with adenocarcinoma (odds ratio, 105; 95% CI, 23-487). Human papillomavirus 16 was associated most strongly with squamous cell carcinoma (odds ratio, 30; 95% CI, 12-77). More than three lifetime sexual partners was a risk factor for adenocarcinoma (odds ratio, 2.1; 95% CI, 1.1-4.0) and squamous cell carcinoma (odds ratio, 3.0; 95% CI, 1.6-5.9). Even being pregnant was associated inversely with adenocarcinoma (odds ratio, 0.4; 95% CI, 0.2-0.8). Five or more pregnancies was associated with squamous cell carcinoma (odds ratio, 2.2; 95% CI, 0.9-5.4)., Conclusion: The relative importance of human papillomavirus genotypes 16 and 18 and the reproductive co-factor differences suggest distinct causes for cervical adenocarcinoma and squamous cell carcinoma.

Objective: We investigated the associations of folate, methionine, and alcohol intake, as well as combinations of these factors, with risk of colorectal cancer (CRC)., Methods: We assessed diet using a 62-item food-frequency questionnaire among 45,264 women in the Breast Cancer Detection Demonstration Project (BCDDP) Follow-up Study. After an average of 8.5 years of follow-up, 490 cases of CRC were identified., Results: Dietary folate showed only a slight inverse association with the risk of CRC (RR = 0.86, 95% CI 0.65-1.13 for high vs. low quintile, p for trend = 0.14), and the association for total folate was null. Consuming more than two servings of alcohol per day was only slightly associated with CRC in this cohort (RR = 1.16, 95% CI 0.63-2.14). Combinations of high alcohol and low total folate did not result in a higher risk of CRC. There was no association between methionine and colorectal cancer., Conclusions: This study shows limited association between alcohol intake and CRC. The non-association of total folate and methionine with CRC, and the null results from the combined folate and alcohol analyses, suggest that what effect alcohol may have on CRC is unrelated to the methyl-group metabolism pathway.

Context: The association between menopausal hormone replacement therapy and ovarian cancer is unclear., Objective: To determine whether hormone replacement therapy using estrogen only, estrogen-progestin only, or both estrogen only and estrogen-progestin increases ovarian cancer risk., Design: A 1979-1998 cohort study of former participants in the Breast Cancer Detection Demonstration Project, a nationwide breast cancer screening program., Setting: Twenty-nine US clinical centers., Participants: A total of 44 241 postmenopausal women (mean age at start of follow-up, 56.6 years)., Main Outcome Measure: Incident ovarian cancer., Results: We identified 329 women who developed ovarian cancer during follow-up. In time-dependent analyses adjusted for age, menopause type, and oral contraceptive use, ever use of estrogen only was significantly associated with ovarian cancer (rate ratio [RR], 1.6; 95% confidence interval [CI], 1.2-2.0). Increasing duration of estrogen-only use was significantly associated with ovarian cancer: RRs for 10 to 19 years and 20 or more years were 1.8 (95% CI, 1.1-3.0) and 3.2 (95% CI, 1.7-5.7), respectively (P value for trend <.001), and we observed a 7% (95% CI, 2%-13%) increase in RR per year of use. We observed significantly elevated RRs with increasing duration of estrogen-only use across all strata of other ovarian cancer risk factors, including women with hysterectomy. The RR for estrogen-progestin use after prior estrogen-only use was 1.5 (95% CI, 0.91-2.4), but the RR for estrogen-progestin-only use was 1.1 (95% CI, 0.64-1.7). The RRs for less than 2 years and 2 or more years of estrogen-progestin-only use were 1.6 (95% CI, 0.78-3.3) and 0.80 (95% CI, 0.35-1.8), respectively, and there was no evidence of a duration response (P value for trend =.30)., Conclusion: Women who used estrogen-only replacement therapy, particularly for 10 or more years, were at significantly increased risk of ovarian cancer in this study. Women who used short-term estrogen-progestin-only replacement therapy were not at increased risk, but risk associated with short-term and longer-term estrogen-progestin replacement therapy warrants further investigation.

Background: Recent findings have cast doubt on the hypothesis that high intakes of fruit and vegetables are associated with a reduced risk of colorectal cancer., Objective: In a large prospective cohort of women, we examined the association between fruit and vegetable intakes and colorectal cancer., Design: Between 1987 and 1989, 45490 women with no history of colorectal cancer satisfactorily completed a 62-item Block-National Cancer Institute food-frequency questionnaire. During 386142 person-years of follow-up, 314 women reported incident colorectal cancer, searches of the National Death Index identified an additional 106 colorectal cancers, and a match with state registries identified another 65 colorectal cancers for a total of 485 cases. We used Cox proportional hazards regression analysis to estimate the relative risks (RRs) and 95% CIs in both energy-adjusted and fully adjusted models., Results: In models using the multivariate nutrient-density model of energy adjustment, RRs for increasing quintile of fruit consumption indicated no significant association with colorectal cancer [RR (95% CI)]: 1.00 (reference), 0.94 (0.70, 1.26), 0.85 (0.63, 1.15), 1.07 (0.81, 1.42), and 1.09 (0.82, 1.44). For vegetable consumption, there was also no significant association in the multivariate nutrient-density model with increasing quintiles of consumption: 1.00 (reference), 0.77 (0.58, 1.02), 0.83 (0.63, 1.10), 0.90 (0.69, 1.19), and 0.92 (0.70, 1.22). Additionally, 3 alternative models of energy adjustment showed no significant association between increases in vegetable intake and the risk of colorectal cancer., Conclusion: Although the limitations of our study design and data merit consideration, this investigation provides little evidence of an association between fruit and vegetable intakes and colorectal cancer.

Breast cancer accounts for one-third of cancer diagnoses and 15% of cancer deaths in U.S. women. Its 192,000 cases and 40,000 deaths in 2001 make it the most common incident cancer (excluding superficial skin cancers) and second leading cause of cancer death. Over one-half of the 300,000 breast cancer deaths worldwide in 1990 (the latest year with such data) occurred in developed countries, but annual mortality rates ranged from 27/100,000 women in northern Europe to 4/100,000 women in Asia. Incidence data are less complete, although 1988-1992 rates varied threefold: low in Asia, intermediate in South America and Eastern Europe, and high in North America and Western Europe. Migrant studies suggest that lifestyle factors largely explain these international differences. U.S. incidence rates are generally 20%-40% higher in white women than in non-white women, but are higher in young (under age 40) black women than in young white women. Incidence rates rose in the 1970s, leveled off in the 1990s, and are declining for young women. Women in some areas of the northeast U.S. have twofold higher mortality than that of other U.S. women, but reproductive and socioeconomic characteristics explain much of that difference. In the 1970s and 1980s, mortality rates held steady in developed countries but rose in developing countries. Since 1987 mortality rates fell by 25% as a result of earlier detection and improved treatment. Age-period-cohort analyses indicate that changes in recognized risk factors may affect mortality patterns. Continued analysis of international and intranational trends may reveal targets for multidisciplinary intervention and prevention efforts.

A case-control study was conducted among 205 women in Michigan and Ohio who were diagnosed with undifferentiated connective tissue disease (UCTD) to investigate the significance of self-reported past exposures to implanted silicone-containing or non-silicone-containing medical devices. The 205 UCTD cases were compared with 2,095 controls who were sampled by random digit dialing. When silicone-containing devices, including shunts and catheters, were analyzed collectively, a significant association was observed (odds ratio (OR) = 2.81, 95% confidence interval (CI): 1.34, 5.89). The odds ratio for exposure to breast implants was increased, but not significantly (OR = 2.22, 95% CI: 0.65, 7.57). Among the non-silicone-containing devices, artificial joints (OR = 5.01, 95% CI: 1.60, 15.71) and orthopedic metallic fixation devices (OR = 1.95, 95% CI: 1.05, 3.60) were associated with UCTD. The estimations of risk associated with implanted medical devices in UCTD cases were explored in a comparison with 660 scleroderma patients who were ascertained concurrently in Michigan and Ohio. In general, the associations that were observed with non-silicone-containing devices, and more specifically with the fixation devices, persisted in the comparison of UCTD cases with scleroderma patients. The studies conducted among populations in Michigan and Ohio are intended to stimulate new hypotheses, innovative approaches, and the fostering of understanding of the environmental determinants of autoimmune disease.

Background: Studies suggest that increased levels of physical activity might decrease the risk of prostate cancer. We ascertained lifetime measures of activity in a population-based case-control study of prostate cancer in Shanghai, China to investigate physical activity in a population where the incidence of prostate cancer is low but rising., Methods: In all, 238 men with prostate cancer, diagnosed 1993-1995, were identified through a rapid reporting system. A second group of 206 men with benign prostatic hyperplasia (BPH) was matched to prostate cancer cases, and 471 age-matched and population-based controls were identified from urban Shanghai. Through personal interviews, we ascertained all daily, occupational, and recreational activities at ages 20-29, ages 40-49, and in 1988 to generate hours spent sleeping, sitting, in moderate activity, and in vigorous activity. Time spent per week in different activities was converted to metabolic equivalents (MET-h) and energy expended., Results: Time spent in, MET-h of, and energy expended in physical activities were not consistently related to either prostate cancer or BPH when compared to controls. Few men reported regular vigorous activity. Occupational activity, based on an energy expenditure index using job titles, was suggestively associated with a decreased risk of BPH, but not associated with prostate cancer. Associations did not vary according to age or stage of prostate cancer at diagnosis., Conclusions: Our results, based on regular physical activity, occupational activity, hours in activities, MET-h, and energy expended, did not support a protective role of physical activity in prostate cancer or BPH for men in a low-risk population.

As human papillomavirus (HPV) becomes accepted as the central cause of cervical cancer, longitudinal studies are shifting focus away from causality to a more detailed investigation of the natural history of HPV infections. These studies commonly require repeated samples for HPV testing over several years, usually collected during a pelvic exam, which is inconvenient to the participants and costly to the study. To alleviate the inconvenience and cost of repeated clinic visits, it has been proposed that women collect cervicovaginal cells themselves, hopefully increasing participation in the natural history studies. We evaluated the technical feasibility of self-collection of cervicovaginal cells using a Dacron swab for HPV DNA detection. We compared the self-collected swab sample and two clinician-administered swab samples (one from the endocervix and another from the ectocervix) from a total of 268 women participating in a case-control study of adenocarcinoma and squamous cell carcinomas of the uterine cervix (111 cases and 157 controls). HPV DNA was detected and genotyped using an L1 consensus PCR assay. The overall agreement between the clinician- and self-collected swabs was excellent [88.1%; kappa = 0.73 (95% confidence interval (CI), 0.61-0.85)]. The correlation was highest between the two clinician-administered swabs [kappa = 0.81 (95% CI, 0.69-0.93)] but was still excellent when comparing either clinician-administered swab to the self-administered sample [kappa = 0.75 (95% CI, 0.63-0.87) and 0.67 (95% CI, 0.55-0.79) for ectocervix and endocervix, respectively]. The type-specific agreement between samples was higher for high-risk, or cancer-associated, HPV genotypes than for low risk, noncancer-associated HPV genotypes when comparing the self-administered swab sample to the clinician-administered swab sample (kappa = 0.78 for high-risk versus 0.66 for low-risk HPV infections, t = -1.45, P = 0.15). The decrease in agreement for low risk types was largely attributable to an increased detection of these types in the self-administered sample (McNemar's chi2 = 6.25, P = 0.01 for clinician- versus self-administered swab comparisons). The agreement did not vary significantly by age, menopausal status, case status, or clinic center. We have demonstrated that a self-collected Dacron swab sample of cervicovaginal cells is a technically feasible alternative to clinician-administered cervical cell collection in natural history studies of HPV and cervical cancer.

Objectives: Few studies of smoking and cervical carcinoma have addressed the rare cervical adenocarcinomas or used DNA-based tests to control for human papillomavirus (HPV) infection., Methods: This multicenter case-control study included 124 adenocarcinoma cases, 307 community controls (matched on age, race, and residence to adenocarcinoma cases), and 139 squamous carcinoma cases (matched on age, diagnosis date, clinic, and disease stage to adenocarcinoma cases). Participants completed risk-factor interviews and volunteered cervical samples for PCR-based HPV testing. Polychotomous logistic regression generated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for both histologic types., Results: Eighteen percent of adenocarcinoma cases, 43% of squamous carcinoma cases, and 22% of controls were current smokers. After control for HPV and other questionnaire data, adenocarcinomas were consistently inversely associated with smoking (e.g. current: OR = 0.6, 95% CI 0.3-1.1; > or = 1 pack per day: OR = 0.7, 95% CI 0.4-1.3), while squamous carcinomas were positively associated with smoking (e.g. current: OR = 1.6, 95% CI 0.9-2.9; > or = 1 pack per day: OR = 1.8, 95% CI 1.0-3.3). Results in analyses restricted to HPV-positive controls were similar., Conclusion: Smoking has opposite associations with cervical adenocarcinomas and squamous carcinomas. Although both histologic types are caused by HPV and arise in the cervix, etiologic co-factors for these tumors may differ.

Objective: Surgical sterilization is a common method of contraception among U.S. women. Most surgical sterilizations are tubal ligations, but few studies have investigated their potential impact on endometrial cancer risk., Methods: A case-control study included 405 women diagnosed with endometrial cancer at 5 U.S. medical centers between 1987 and 1990 and 297 age-, race-, and location-matched controls who were identified by random-digit-dialing. Questionnaires ascertained information on tubal sterilization, and logistic regression models generated odds ratios (ORs) to estimate relative risk., Results: The OR and 95% confidence interval for tubal sterilization, which was reported by 47 cases and 40 controls, was 0.9 (0.6-1.4) before adjustment and 1. 4 (0.8-2.4) after adjustment for age, parity, and oral contraceptive use. Age at surgery, years since surgery, or calendar years of surgery were not associated with endometrial cancer, and associations did not vary according to parity or stage of disease at diagnosis., Conclusions: Tubal sterilization is not substantially associated with endometrial cancer., (Copyright 2000 Academic Press.)

Introduction: Exogenous hormones may influence the development of cervical adenocarcinomas. Incidence rates of adenocarcinomas and use of noncontraceptive hormones have increased since the 1970s, but few studies have investigated this potential relationship., Methods: We conducted a multicenter case-control study of 124 women with adenocarcinomas, 139 women with squamous cell carcinomas matched on age, diagnosis date, clinic, and stage of disease (in situ or invasive) to adenocarcinoma cases, and 307 healthy community controls who were also matched on age, ethnicity, and residence to adenocarcinoma cases. Participants completed in-person interviews regarding exogenous hormone use before diagnosis and other risk factors and volunteered cervical samples for human papillomavirus (HPV) testing via a PCR-based method. Odds ratios (ORs) with 95% confidence intervals (CIs) estimated relative risks., Results: Only 13 adenocarcinoma cases (10.5%), 7 squamous carcinoma cases (5%), and 20 controls (6.5%) had used noncontraceptive hormones for menopausal symptoms, irregular periods, or disease prevention; most use was short-term, former use. Ever-use was associated with adenocarcinomas (OR = 2.1, 95% CI 0.95-4.6) but not squamous carcinomas (OR = 0.85, 95% CI 0.34-2.1). No trends were seen with duration of use or ages at first use, but unopposed estrogens were positively associated with adenocarcinomas (OR = 2.7). Unopposed estrogens remained associated with adenocarcinomas (OR = 2.0) when analyses were restricted to the HPV-positive controls. Menopausal status was not associated with adenocarcinomas or squamous carcinomas and did not modify the other associations., Conclusion: Although small numbers warrant tentative conclusions, exogenous estrogens, especially unopposed estrogens, were positively associated with adenocarcinomas. Noncontraceptive hormones were negatively but weakly associated with squamous carcinomas., (Copyright 2000 Academic Press.)

To assess the hypothesis that oral contraceptives (OCs) increase the risk of cervical adenocarcinomas, we conducted a six-center case-control study of 124 patients with adenocarcinomas, 139 with squamous cell carcinomas, and 307 population controls. Women between the ages of 18 and 69 who were newly diagnosed with cervical adenocarcinomas between 1992 and 1996 were eligible. Healthy female controls and a second case group of incident cervical squamous cell carcinomas were matched to the adenocarcinoma cases. All participants were interviewed regarding OCs, other risk factors for cervical carcinoma, and utilization of cytological screening, and a PCR-based test determined HPV genotype of cervical samples for both case groups and controls. Use of OCs was positively and significantly associated with adenocarcinomas and positively but weakly associated with squamous cell carcinomas. Associations between OCs and invasive adenocarcinomas (n = 91), squamous cell carcinoma in situ (n = 48), and invasive squamous cell carcinomas (n = 91) disappeared after accounting for HPV infection, sexual history, and cytological screening, but a positive association remained between current use of OCs and cervical adenocarcinoma in situ (n = 33). This association persisted after stratification by screening and sexual history and after restriction according to HPV status, but small numbers made it difficult to exclude detection bias, selection bias, or residual confounding by HPV as potential explanations Current OC use was associated with cervical adenocarcinomas in situ, but we saw no other evidence that OCs independently increase the risk of cervical carcinomas.

Occupational solvent exposure may increase the risk of connective tissue disease (CTD). The objective of this case-control study was to investigate the relation between undifferentiated connective tissue disease (UCTD) and solvent exposure in Michigan and Ohio. Women were considered to have UCTD if they did not meet the American College of Rheumatology classification criteria for any CTD but had at least two documented signs, symptoms, or laboratory abnormalities suggestive of a CTD. Detailed information on solvent exposure was ascertained from 205 cases, diagnosed between 1980 and 1992, and 2,095 population-based controls. Age-adjusted odds ratios (OR) and 95 percent confidence intervals (CI) were calculated for all exposures. Among 16 self-reported occupational activities with potential solvent exposure, furniture refinishing (OR = 9.73, 95 percent CI 1.48-63.90), perfume, cosmetic, or drug manufacturing (OR = 7.71, 95 percent CI 2.24-26.56), rubber product manufacturing (OR = 4.70, 95 percent CI 1.75-12.61), work in a medical diagnostic or pathology laboratory (OR = 4.52, 95 percent CI 2.27-8.97), and painting or paint manufacturing (OR = 2.87, 95 percent CI 1.06-7.76) were significantly associated with UCTD. After expert review of self-reported exposure to ten specific solvents, paint thinners or removers (OR = 2.73, 95 percent CI 1.80-4.16) and mineral spirits (OR = 1.81, 95 percent CI 1.09-3.02) were associated with UCTD. These results suggest that exposure to petroleum distillates increases the risk of developing UCTD.

Objective: To examine racial differences in disease onset, extent, manifestations, and survival among women with scleroderma., Methods: A retrospective cohort study of women with scleroderma, diagnosed in Michigan between 1980 and 1991, was conducted. Clinical, laboratory, and demographic data were abstracted from the patients' medical records., Results: A total of 514 women with scleroderma were identified: 117 (23%) were black and 397 (77%) were white. Among black women, the mean age at diagnosis was lower (44.5 years versus 51.5 years; P < 0.001) and diffuse disease was more common (49.6% versus 24.9%; P < 0.001) than among white women. The overall incidence of scleroderma was 14.1 per million per year: 22.5 per million per year in black women versus 12.8 per million per year in white women (P < 0.001). Pericarditis (P = 0.009), pulmonary hypertension (P < 0.001), pleural effusions (P = 0.01), myositis (P = 0.02), and an erythrocyte sedimentation rate >40 mm/hour (P < 0.001) were more frequent among black women, while white women were more likely to have digital infarctions (P < 0.001). Survival at 7 years from diagnosis was 72.5% among black women and 77.6% among white women. Age-adjusted survival was significantly reduced among black women (P = 0.033), most likely because of increased diffuse involvement. Survival among those with renal or pulmonary involvement was also significantly reduced., Conclusion: Black women with scleroderma were significantly more likely than white women to develop diffuse disease, be diagnosed at a younger age, have a higher incidence of inflammatory features, and have a worse age-adjusted survival rate.