A prospective cohort study of cigarette smoking and the risk of endometrial cancer

Case-control studies have shown inverse associations between cigarette smoking and endometrial cancer risk. However, two small prospective cohort studies have not clearly supported an association. Moreover, quantitative measures of smoking have been examined infrequently. Our aim was to study the association between smoking and endometrial cancer risk in a large prospective cohort. We used proportional hazards models to estimate hazard ratios relating cigarette smoking to endometrial cancer risk among 70 591 women aged 40-59 years at recruitment into a randomised controlled trial of mammography screening for breast cancer. During an average of 10.6 years of follow-up (751 833 person-years), a total of 403 women were diagnosed with incident endometrial cancer. We found that a reduced endometrial cancer risk was evident only among women who currently smoked 20 cigarettes per day or more (hazard ratio=0.62, 95% CI=0.42-0.92, P for trend=0.03). There was some suggestion of an inverse association with smoking duration, but this was less clear. The association did not vary with menopausal status, relative body weight, or the use of hormone replacement therapy, but it appeared to be stronger among parous than nulliparous women. The underlying biological mechanisms of this association remain unclear.     

Patterns of postmenopausal progestin use with estrogen in relation to endometrial cancer (United States)

Objective: To investigate the risk of endometrial cancer associated with various regimens of postmenopausal hormone therapy. Methods: Data from a population-based case–control study were analysed that included 591 women newly diagnosed with endometrial cancer, aged 40–79, and who were reported to Wisconsin's statewide tumor registry in 1991–1994. Similarly aged population controls (n = 2045) were randomly selected from lists of licensed drivers and Medicare beneficiaries. Information on hormone use and other factors was obtained through telephone interviews. Results: Ever use of estrogen–progestin hormones was associated with increased endometrial cancer compared to women who had never used hormones; the increase per year of use was 7% (95% confidence interval 1–13%). Both cyclic (<10 days per month) and continuous progestin used with estrogen were associated with comparable twofold increases in risk relative to non-users. There was no increased risk associated with progestin used for 10–21 days per month. Conclusions: Both continuous and cyclic progestin regimens are associated with a much lower risk of endometrial cancer than estrogen alone. However, many women using these regimens remain at significantly increased risk of endometrial cancer.     

Obesity,body size,and risk of postmenopausal breast cancer: the Women's Health Initiative (United States)

OBJECTIVE: Body size is an important modifiable risk factor for breast cancer. Although obesity has generally been found to be associated with increased risk for postmenopausal breast cancer, there remain questions concerning the role of body fat distribution, lifetime weight history, and effects within specific subgroups of women.METHODS: We assessed the relationship of several anthropometric measures and risk of postmenopausal breast cancer in 85,917 women aged 50–79 at entry in the Women's Health Initiative Observational Study. Women were enrolled during 1993–1998 at 40 clinics in the US and 1030 developed invasive breast cancer by April 2000. Upon entry, trained clinical center staff measured each woman's height, weight, and waist and hip circumference.RESULTS: Anthropometric factors were not associated with breast cancer among women who had ever used hormone replacement therapy (HRT). Among HRT non-users, heavier women (baseline body mass index (BMI) > 31.1) had an elevated risk of postmenopausal breast cancer (relative risk (RR) = 2.52; 95% confidence interval (CI) = 1.62–3.93), compared to slimmer women (baseline BMI 22.6). The elevation in risk associated with increasing BMI appeared to be most pronounced among younger postmenopausal women. Change in BMI since age 18, maximum BMI, and weight were also associated with breast cancer in HRT non-users. While both waist and hip circumference were associated with breast cancer risk, their ratio, a measure of fat distribution, was not (RR = 1.33; 95% CI = 0.88–2.01).CONCLUSIONS: Our study confirms previously reported findings that generalized obesity is an important risk factor for postmenopausal breast cancer, but only among women who have never taken HRT. Lifetime weight gain is also a strong predictor of breast cancer. Waist to hip ratio, a measure of weight distribution, does not appear to be related to postmenopausal breast cancer risk.     

Cigarette smoking and breast cancer risk among young women (United States)

Objectives: To evaluate whether heavy cigarette smoking as a teenager or long-term smoking increases breast cancer risk or, alternatively, whether smoking acts as an anti-estrogen and reduces risk.Methods: Data from a multi-center, population-based, case-control study among women under age 55 were analyzed.Results: Among women under age 45, there was a modest inverse relation with current (OR=0.82, 95% CI=0.67, 1.01) but not past (OR=0.99, 95% CI=0.81, 1.21) smoking. Odds ratios were decreased for current smokers who began at an early age (0.59 for15, 95% CI=0.41, 0.85) or continued for long periods of time (0.70 for >21 years, 95% CI=0.52, 0.94). In subgroup analyses, reduced odds ratios were observed among current smokers who were ever users of oral contraceptives (0.79, 95% CI=0.63, 0.98), were in the lowest quartile of adult body size (0.53, 95% CI=0.34, 0.81), or never or infrequently drank alcohol (0.68, 95% CI=0.47, 0.98). Among women ages 45-54, there was little evidence for an association with smoking.Conclusions: These results suggest that breast cancer risk among women under age 45 may be reduced among current smokers who began smoking at an early age, or long-term smokers, but require confirmation from other studies.     

Dietary iron and haem iron intake and risk of endometrial cancer: a prospective cohort study

We used data from a large cohort study of Canadian women to assess the association of meat intake and dietary intake of iron and haem iron with risk of endometrial cancer. Among 34,148 women with an intact uterus at baseline and followed for a mean of 16.4 years, we identified 426 incident endometrial cancer cases. Data from a food frequency questionnaire administered at baseline were used to calculate intake of all meats, red meat, total dietary iron, iron from meat, haem iron, and non-haem iron. Analyses were carried out using Cox proportional hazards models with adjustment for known risk factors and covariates. We found no association of intake of meat or any of the dietary iron-related variables with risk of endometrial cancer.     

Postmenopausal hormone therapy and risk of breast cancer by histologic type (United States)

Objective: Postmenopausal hormone use and risk of breast cancer by histopathology was examined in a large multi-centered population-based case–control study. Methods: Women younger than 75 years newly diagnosed with invasive breast cancer between 1988 and 1991 were identified from statewide tumour registries in Wisconsin, Massachusetts, New Hampshire, and Maine. Only postmenopausal women were included in this analysis. Breast cancer cases (lobular (n = 219), ductal, NOS (n = 2172), and specific ductal subtypes (n = 242)) were compared with randomly selected population controls (n = 3179) using adjusted multi-variable polytomous logistic regression to estimate odds ratios (OR) and 95% confidence intervals (95%CI) for each histology. Results: Lobular carcinoma was associated with recent (within 2 years) estrogen therapy (OR:1.8, 95%CI: 1.0–3.4) and recent use of combined estrogen-plus-progestin therapy (OR:3.6, 95%CI: 1.8–7.6). Risk of ductal carcinoma was not associated with recent use of either estrogen alone (OR: 0.9, 95%CI: 0.7–1.2) or combined therapy (OR:0.9, 95%CI: 0.6–1.3). No associations were found with ductal subtypes. Conclusions: The association between postmenopausal hormone use and risk of breast cancer may depend on histopathology. Of particular interest is the association between combined hormone therapy and increased risk of lobular carcinoma. This lesion is increasingly common but, nonetheless, comprises fewer than 10% of invasive breast cancers.     

Reproductive factors and postmenopausal hormone use in relation to endometrial cancer risk in the Nurses' Health Study cohort 1976–2004

Endometrial cancer is a disease primarily driven by cumulative exposure to estrogen unopposed by progesterone. Reproductive factors associated with changes in endogenous hormone levels and use of exogenous hormones such as postmenopausal hormones influence the risk of disease. The authors used the Nurses' Health Study, comprised of 121,700 nurses, to assess the above associations. Over 28 years of follow‐up, 778 adenocarcinoma cases were diagnosed and 1,850,078 person‐years were accumulated. Cox proportional hazards models were used to estimate relative risks (RR) and 95% confidence intervals (CI). A late age at menarche decreased the risk independent of body mass index (BMI) (P‐trend = 0.02). A late age at menopause increased cancer risk (P‐trend = 0.0003). An advanced age at last birth reduced the risk (P‐trend < 0.0001), however, an inverse association with age at first birth and parity diminished after adjustment for age at last birth. Compared with never users, an increased risk was observed among long‐term (≥5 years) users of both estrogen (E) (RR = 7.67, 95% CI: 5.57, 10.57) and combined estrogen plus progesterone (E+P) (RR = 1.52, 95% CI: 1.03, 2.23). Normal‐weight (BMI < 25) women had the highest risk following E or E+P use (P‐interaction‐E = 0.0008, P‐interaction‐E+P = 0.02). The findings from this study underscore the importance of hormonal mechanisms in endometrial carcinogenesis.     

Cytochrome P450 1A1, cigarette smoking,and risk of endometrial cancer (United States)

Cytochrome P450 1A1 (CYP1A1) is involved in the metabolism of estradiol and the activation of polycyclic aromatic hydrocarbons found in tobacco products. Polymorphic variation in CYP1A1 activity may modify susceptibility to endometrial cancer through the oxidative metabolism of estradiol and the activation of tobacco-smoke constituents. We prospectively evaluated the associations between three common CYP1A1 polymorphisms and endometrial cancer risk, as well as the potential modification of these associations by cigarette smoking, in a case–control study nested within the Nurses’ Health Study. We investigated the MspI restriction-site polymorphism, a C → A transversion at nucleotide 4887 (Thr461Asn) and a A → G transition at nucleotide 4889 (Ile462Val) among 456 women with endometrial cancer and 1,134 matched controls. We used conditional logistic regression to calculate the adjusted odds ratios (OR) and 95% confidence intervals (CI) to quantify the risk of endometrial cancer among subjects who had at least one variant allele compared with that of subjects homozygous for the wild-type allele. We did not observe any statistically significant associations between the MspI, Thr461Asn or Ile462Val polymorphisms and endometrial cancer risk or any significant effect modification by cigarette-smoking status. These data suggest that these three polymorphisms are not important in determining genetic susceptibility to endometrial cancer, although larger sample sizes are needed to confirm these findings.     

Obesity and the risk of prostate cancer (United States)

The role of obesity in prostate cancer etiology remains controversial. A recent report suggested that obese men younger than age 60 may have a lower risk of developing prostate cancer than men the same age who are not obese. The current study used a nested, matched case–control study design and data collected in the General Practice Research Database between January 1991 and December 2001 to assess the association between body mass index (BMI) and the risk of incident prostate cancer. Seven hundred and thirty cases of prostate cancer with adequate information on BMI were identified and matched to 2740 controls on age, sex, general practice, and index date. Obese men (BMI ≥ 30.0 kilograms [kg]/square of height in meters [m²]) were at lower risk of developing prostate cancer (AOR=0.78, 95% CI: 0.56, 1.09) compared to normal weight men (BMI=23.0–24.9 kg/m²), and the data best fit an inverse quadratic model for the relation between BMI and the risk of prostate cancer. This study provides modest support for a protective association between obesity and the risk of incident prostate cancer.     

Risk of endometrial cancer in relationship to cigarette smoking: results from the EPIC study

Current epidemiologic evidence indicates that cigarette smoking reduces the risk of endometrial cancer. We examined data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to analyze further aspects of the smoking-endometrial cancer relationship, such as possible modifying effects of menopausal status, HRT use, BMI and parity. In a total of 249,986 women with smoking exposure and menopausal status information, 619 incident endometrial cancer cases were identified during 1.56 million person-years of follow-up. Among postmenopausal women, the hazard ratio (HR) for current smokers versus never smokers was 0.70 (95% CI = 0.53-0.93), while it was 1.75 (95% CI = 1.13-2.70) among premenopausal women at recruitment. After adjustment for risk factors, the HR for postmenopausal women was slightly attenuated to 0.78 (95% CI = 0.59-1.03). No heterogeneity of effect was observed with HRT use or BMI. Among premenopausal women, current smokers of more than 15 cigarettes per day or who smoked for 30 years or more at the time of recruitment had a more than 2-fold increased risk of endometrial cancer compared to never smokers (HR = 2.54; 95% CI = 1.47-4.38 and HR = 2.23; 95% CI = 1.04-4.77, respectively). Past smoking was not associated with endometrial cancer risk, either among pre- or postmenopausal women. In this prospective study, we observed an increased risk of endometrial cancer with cigarette smoking in premenopausal women. The reduction of endometrial cancer risk observed among postmenopausal women does not have direct public health relevance since cigarette smoking is the main known risk factor for cancer.     

Hormone Replacement Therapy,Reproductive History,and Colorectal Adenomas: Data from the Prostate,Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial (United States)

Objective Findings from some epidemiologic studies of colorectal cancer and adenoma suggest that the protective effect of post-menopausal hormone replacement therapy (HRT) may differ across categories of age and body mass index (BMI). We conducted an analysis of women participating in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial to investigate the relationship between HRT use and prevalent adenoma, both overall and across different population subgroups.Methods Women aged 55–74 were randomized to screening by flexible sigmoidoscopy at ten PLCO screening centers between September 1993 and September 2001. We identified 1468 women with at least one left-sided adenoma and 19,203 without adenoma or colorectal cancer. Information about HRT and reproductive factors was obtained from a self-administered questionnaire.Results Compared to never use of HRT, current use was associated with a decreased prevalence of left-sided adenoma (odds ratio (OR) 0.85; 95% confidence interval (CI) 0.75–0.97). We found no evidence of dose–response with increasing duration of use for current or former users. The association with current HRT use was stronger among women aged 65+ (OR 0.69; 95% CI 0.56–0.84), with a BMI<30 (OR 0.82; 95% CI 0.71–0.95) and who regularly use aspirin or ibuprofen (OR 0.77; 95% CI 0.65–0.91). Other reproductive factors were not significantly associated with adenoma prevalence.Conclusions Our findings suggest that current HRT use may protect against colorectal adenoma, and that this protective effect is short-lived following cessation of use.     

Breast cancer risk factors in relation to breast density (United States)

Objectives Evaluate known breast cancer risk factors in relation to breast density. Methods We examined factors in relation to breast density in 144,018 New Hampshire (NH) women with at least one mammogram recorded in a statewide mammography registry. Mammographic breast density was measured by radiologists using the BI-RADS classification; risk factors of interest were obtained from patient intake forms and questionnaires. Results Initial analyses showed a strong inverse influence of age and body mass index (BMI) on breast density. In addition, women with late age at menarche, late age at first birth, premenopausal women, and those currently using hormone therapy (HT) tended to have higher breast density, while those with greater parity tended to have less dense breasts. Analyses stratified on age and BMI suggested interactions, which were formally assessed in a multivariable model. The impact of current HT use, relative to nonuse, differed across age groups, with an inverse association in younger women, and a positive association in older women (p < 0.0001 for the interaction). The positive effects of age at menarche and age at first birth, and the inverse influence of parity were less apparent in women with low BMI than in those with high BMI (p = 0.04, p < 0.0001 and p = 0.01, respectively, for the interactions). We also noted stronger positive effects for age at first birth in postmenopausal women (p = 0.004 for the interaction). The multivariable model indicated a slight positive influence of family history of breast cancer. Conclusions The influence of age at menarche and reproductive factors on breast density is less evident in women with high BMI. Density is reduced in young women using HT, but increased in HT users of age 50 or more.     

Menopausal estrogen and estrogen-progestin replacement therapy and risk of breast cancer (United States)

This study examines the relationship between menopausal estrogen and estrogen-progestin replacement therapy and risk of breast cancer, focusing on whether associations differ according to whether the tumors arein situ or invasive. Data are from a prospective study conducted 1980–89 on 49,017 selected participants in the Breast Cancer Detection Demonstration Project, a five-year screening program conducted between 1973 and 1980 in the United States. Overall, the rate ratio for estrogen-only use compared with no-hormone use was 1.0, and that for the estrogen-progestin combination was 1.2 (95 percent confidence interval [CI]=1.0–1.6). However, the associations differed according to whether the tumors werein situ or invasive. The rate ratios ofin situ breast cancer associated with use of estrogens alone and the combination regimen were 1.4 (CI=1.0–2.0) and 2.3 (CI=1.3–3.9), respectively. Duration of estrogen-only use also was associated with risk ofin situ tumors, with users for 10 or more years at twice the risk of nonusers (P-value for trend test =0.02). Duration of use was not associated with risk of in vaisve cancer. Our results are consistent with the hypothesis that hormone replacement therapy is related to earlier-stage breast cancer; however, the possibility that the results reflect increased breast cancer surveillance among those taking hormones cannot be ruled out.     

A prospective study of menopausal hormones and risk of colorectal cancer (United States)

The relation of colorectal cancer and its subsites with use ofmenopausal hormones was evaluated in the United States among 40,464postmenopausal women, 41 to 80 years of age, who initially volunteered for anationwide breast-cancer screening program and were followed for an averageof 7.7 years. Ever-use of menopausal hormones was not associated with risk oftotal colorectal cancers (relative risk [RR] = 0.99, 95 percent confidenceinterval [CI] = 0.79-1.2) or cancers of the colon (RR = 1.1, CI = 0.81-1.6)or rectum (RR = 1.1, CI = 0.59-1.9). Recent hormone users, however, had asmall nonsignificant reduction in risk of colorectal cancer (RR = 0.78, CI =0.55-1.1), which was most pronounced for distal colon (RR = 0.68, CI =0.29-1.6) and rectal tumors (RR = 0.64, CI = 0.24-1.7). No effect wasobserved for former hormone users, and risk generally did not vary by timesince last use, type of regimen, or duration of use. However, the reducedrisk for recent users was stronger for users of five or more years'duration. These data show some lowering of colorectal cancer risk amongrecent menopausal hormone users of long duration.     

The associations of adolescent cigarette smoking, alcoholic beverage consumption, environmental tobacco smoke, and ionizing radiation with subsequent breast cancer risk (United States)

Objectives: Studies of breast cancer among survivors of the World War II atomic bomb blasts over Japan suggest that the adolescent breast may be particularly sensitive to carcinogenic insult. To further explore that possibility we examined the relationships of cigarette smoking, alcohol consumption, environmental tobacco smoke (ETS) exposure, and medical treatment with ionizing radiation during adolescence with subsequent breast cancer risk. Methods: Data from the Carolina Breast Cancer Study, a population-based, case–control study of breast cancer in North Carolina women aged 20–74years (864 cases, 790 controls), were analyzed. Results: A modest increase in breast cancer risk was suggested for women who began to smoke cigarettes between the ages of 10 and 14 years (OR: 1.5, CI: 0.9–2.5), and for women exposed to ionizing radiation between ages 10 and 19 years to treat or monitor a medical condition (OR: 1.6, CI: 0.5–2.5). Neither exposure to ETS at home prior to age 18 years (OR: 1.1, CI: 0.9–1.3) nor initiation of alcoholic beverage consumption between ages 10 and 15 years (OR: 1.1, CI: 0.6–1.8) appeared to increase risk. Conclusions: Our results are consistent with previous evidence suggesting that some adolescent exposures could influence future breast cancer risk.     

Overall obesity, abdominal adiposity, diabetes and cigarette smoking in relation to the risk of pancreatic cancer in two Swedish population-based cohorts

We examined the associations of body mass index (BMI), waist circumference, a history of diabetes, and cigarette smoking with risk of pancreatic cancer among 37,147 women and 45,906 men followed up during 560,666 person-years in the Swedish Mammography Cohort and the Cohort of Swedish Men; 136 incident cases of pancreatic cancer were diagnosed. The multivariate rate ratio (RR) of pancreatic cancer for obese women and men (BMI > or =30 kg/m(2)) was 1.81 (95% CI: 1.04-3.15) compared to those with a BMI of 20-25 kg/m(2). For a difference of 20 cm (about two standard deviations) in waist circumference, the multivariate RRs were 1.32 (95% CI: 0.73-2.37) among women and 1.74 (95% CI: 1.00-3.01) among men. Pancreatic cancer risk was associated with history of diabetes (multivariate RR: 1.88; 95% CI: 1.09-3.26) and cigarette smoking (multivariate RR for current compared with never smokers: 3.06; 95% CI: 1.99-4.72). Current smokers of > or =40 pack-years had a five-fold elevated risk compared with never smokers. Risk among past smokers approached the RR for never smokers within 5-10 years following smoking cessation. Findings from this prospective study support positive relationships of overall obesity, abdominal adiposity, diabetes and smoking with risk of pancreatic cancer.     

Diet in the epidemiology of endometrial cancer in Western New York (United States)

Objectives: We examined diet and risk of endometrial cancer among women in the Western New York Diet Study (1986–1991). Methods: Self-reported frequency of use of 172 foods and beverages during the 2 years before the interview and other relevant data were collected by detailed interviews from 232 endometrial cancer cases and 639 controls, frequency-matched for age and county of residence. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by unconditional logistic regression, adjusting for age, education, body mass index (BMI), smoking history, hypertension, diabetes, age at menarche, parity, oral contraceptive use, menopausal status, menopausal estrogen use, and energy. Results: Risks were reduced for women in the highest quartiles of intake of protein (OR 0.4, 95% CI: 0.2–0.9), dietary fiber (OR 0.5, 95% CI: 0.3–1.0), phytosterols (OR 0.6, 95% CI: 0.3–1.0), vitamin C (OR 0.5, 95% CI: 0.3–0.8) folate (OR 0.4, 95% CI: 0.2–0.7), alpha-carotene (OR 0.6, 95% CI: 0.4–1.0), beta-carotene (OR 0.4, 95% CI: 0.2–0.6), lycopene (OR 0.6, 95% CI: 0.4–1.0), lutein + zeaxanthin (OR 0.3, 95% CI: 0.2–0.5) and vegetables (OR 0.5, 95% CI: 0.3–0.9), but unrelated to energy (OR 0.9, 95% CI: 0.6–1.5) or fat (OR 1.6, 95% CI: 0.7–3.4). Conclusions: Our results support previous findings of reduced endometrial cancer risks associated with a diet high in plant foods.     

Reproductive and hormonal factors associated with mammographic breast density by age (United States)

Objectives: We determined the association of certain reproductive and hormonal factors with breast density over decades of life. Methods: Subjects were women age 20–79 years who had a screening mammogram between 1 June 1996 and 1 August 1997, in Seattle, Washington. Women with increased breast density (upper two categories of BI-RADS terminology) (n = 14,432) were compared to those with fatty breasts (lower two categories (n = 14,552). Unconditional logistic regression was used with adjustment for age at mammogram, parity, age at first birth, menopausal status, current use of hormone replacement therapy (HRT), and body mass index. Results: The association of nulliparity with density was evident for women at all ages (odds ratio (OR) and 95% confidence interval (CI) = 1.5 (1.3–1.7) and 1.6 (1.4–1.9) for women age 45 and >65, respectively). Older age at first birth was more strongly associated with density among women >55 than among younger women. The association of current use of HRT with density, but not of former use, increased with age when compared to never users (OR = 1.4 (1.2–1.7) and 2.2 (2.0–2.5) for women age 46–55 and >65, respectively). Conclusions: Results suggest that pregnancy at an early age has a permanent beneficial association with density, while HRT has a transitory adverse association.