Oral contraceptives and endometrial cancer: Do other risk factors modify the association?

The joint effect of use of combination-type oral contraceptives and other exposure factors on risk of endometrial cancer was examined in data from a multicenter case-control study conducted in 5 areas of the United States. Cases were 405 women with histologically confirmed invasive epithelial endometrial cancer first treated at one of 7 participating hospitals. A total of 297 population-based controls of similar age, race, and geographic area were selected as a comparison group. Information on exposure factors was derived from in-person interviews. Combination-type oral contraceptive (COC) use was associated with a significant reduction in risk of endometrial cancer, with an adjusted odds ratio (OR) of 0.4 (95% confidence interval 0.3 to 0.7) for ever compared to never use. Long-term (≥ 10 years) users experienced a markedly lower risk (OR = 0.2). Women who discontinued COC use ≥20 years earlier remained at reduced risk (OR = 0.7) compared with non-users. The negative association with COC use was apparent regardless of the presence or level of several other risk factors for endometrial cancer, including age, menopausal status, parity, obesity, ever-use of menopausal estrogens, smoking history, or history of infertility. The magnitude of the negative association observed in COC users, however, was considerably diminished in women with no full-term births and in women who subsequently used replacement estrogens for 3 or more years. These results provide new evidence that the protective effect of COC use lasts for 20 or more years after use is discontinued, and highlight several sub-groups of users in whom the level of protection is attenuated by the presence of other risk factors for this disease.     

Tamoxifen therapy for breast cancer and endometrial cancer risk.

BACKGROUND: Tamoxifen is effective in treating breast cancer, reduces breast cancer incidence among high-risk women, and is associated with increased endometrial cancer risk. This study was designed to examine the possible modifying effects of endometrial cancer risk factors on the tamoxifen-endometrial cancer association. METHODS: We conducted a case-control study of endometrial cancer (324 case patients and 671 individually matched control subjects) nested within a population-based cohort of patients with breast cancer diagnosed from 1978 through 1992 within four regions of the United States. We obtained information on breast cancer treatment and endometrial cancer risk factors through interviews and reviews of medical records. All P values reported are two-sided. RESULTS: Endometrial cancer risk was associated with tamoxifen therapy for breast cancer (odds ratio = 1.52; 95% confidence interval [CI] = 1. 07-2.17). Risk increased with duration of tamoxifen use (P for trend =.0002). Women with more than 5 years of exposure to tamoxifen had 4. 06-fold greater odds of developing endometrial cancer than nonusers (95% CI = 1.74-9.47). Prior use of estrogen replacement therapy (ERT) increased risk associated with tamoxifen use (P for homogeneity of trends <.0001). Risk associated with tamoxifen use was stronger among heavier women than among thinner women, although trends did not differ statistically (P =.10). Tamoxifen dose-response effects were more pronounced among women with both previous ERT exposure and higher body mass index than among women in other risk groups. CONCLUSIONS: ERT use and obesity, both established endometrial cancer risk factors and markers of estrogen exposure, substantially modify the association between tamoxifen use and endometrial cancer risk among patients with breast cancer. Women with positive ERT histories and those who are obese, when prescribed tamoxifen, may warrant closer surveillance for endometrial cancer than women without such histories.     

Recency,duration, and progestin content of oral contraceptives in relation to the incidence of endometrial cancer (Washington,USA)

Women who have used combined oral contraceptives (COC) have a reduced risk of endometrial cancer relative to that of women who have never used oral contraceptives, but it is unclear whether the size of the reduction is influenced by the progestin content of the preparation. We analyzed data from two population-based case-control studies of endometrial cancer to investigate this question. Among women aged 40 to 59 years who were residents of King or Pierce Counties, Washington (United States), incident cases who were diagnosed during 1975–77 or 1985–87 were identified. Personal interviews were conducted with 316 such women and their responses compared with those of 501 controls who were selected by household surveys or random-digit dialing. A reduced risk of endometrial cancer associated with COC use was present only among users of five or more years' duration, and even then only in women who were not long-term users of unopposed postmenopausal estrogens. Among these women, the relative risk (RR) of endometrial cancer did not differ according to the progestin potency of the COC used: it was equally low for women who had used a COC with low progestin content (RR=0.2, 95 percent confidence interval [CI]=0.1–0.8) as for women who had used a COC with high progestin content (RR=0.3, CI=0.1–0.9). Our results argue that, if the reduced risk of endometrial cancer in long-term users of COCs is due to the progestins contained in these preparations, that amount of progestin in most COCs exceeds the threshold amount needed to produce this beneficial effect.This project was supported by Grant 5R35CA39779 and Contract NO1-CN-05230 from the US National Cancer Institute.     

Hormonal content and potency of oral contraceptives and breast cancer risk among young women

Recent use of oral contraceptive pills is associated with a modest risk of breast cancer among very young women. In this US population-based case-control study, we evaluated whether the excess risk associated with recent oral contraceptive use is ubiquitous for all pill types or attributable to specific oral contraceptive preparations. Hormonal content and potency of combination oral contraceptives used for the longest duration within 5 years of interview for breast cancer cases aged 20-44 years (N=1640) were compared with age-matched community controls (N=1492). Women who recently used oral contraceptives containing more than 35 microg of ethinyl oestradiol per pill were at higher risk of breast cancer than users of lower dose preparations when compared to never users (respective relative risks of 1.99 and 1.27, P(trend)<0.01). This relationship was more marked among women <35 years of age, where risks associated with high- and low-dose ethinyl oestradiol use were 3.62 and 1.91 (P(trend)<0.01), respectively. We also found significant trends of increasing breast cancer risk for pills with higher progestin and oestrogen potencies (P(trend)<0.05), which were most pronounced among women aged <35 years of age (P(trend)<0.01). Risk was similar across recently used progestin types. Our findings suggest that newer low-potency/low oestrogen dose oral contraceptives may impart a lower risk of breast cancer than that associated with earlier high-potency/high-dose preparations.     

Risk of endometrial cancer and estrogen replacement therapy history by CYP17 genotype

Common variants among genes coding for enzymes in sex steroid biosynthetic pathways may influence the risk of endometrial cancer. We examined the association between endometrial cancer risk and estrogen replacement therapy (ERT) by CYP17 genotype using 51 incident cases and 391 randomly selected controls from a multiethnic cohort in Hawaii and Los Angeles, California. The relative risk of endometrial cancer was calculated for ever use versus never use of ERT by CYP17 genotype (TT, TC, and CC). We found that women who reported ever taking ERT were more than twice as likely to develop endometrial cancer as women who never took ERT [odds ratio (OR), 2.24; 95% confidence interval (CI), 1.19-4.23]. Among these women, the risk of endometrial cancer was higher for women homozygous for the CYP17 T allele (OR, 4.10; 95% CI, 1.64-10.3), but not for women with the C allele (OR, 1.31; 95% CI, 0.53-3.21). These preliminary findings suggest that CYP17 or other variants in estrogen biosynthesis or metabolism pathways may be potential markers of endometrial cancer susceptibility due to ERT.     

A prospective study of high-grade cervical neoplasia risk among human papillomavirus-infected women

BACKGROUND: In case-control studies, smoking, parity, and oral contraceptive use have been associated with an increased risk of cervical intraepithelial neoplasia grade 3 (CIN3) and cervical cancer among women who are infected with oncogenic human papillomavirus (HPV). However, these potential risk factors have not been adequately studied in prospective studies. METHODS: We studied 1812 women who were enrolled in a 10-year prospective study of cervical neoplasia at Kaiser Permanente in Portland, Oregon, and who at enrollment had tested positive for oncogenic HPV DNA and had responded to a questionnaire that included questions on smoking, oral contraceptive use, and parity. Absolute risks and crude relative risks (RRs) with 95% confidence intervals (CIs) for CIN3 or cervical cancer were computed for three time intervals (0-8, 9-68, and 69-122 months after enrollment) using the Kaplan-Meier method. Conditional logistic regression models were used to control for factors that may have influenced our risk estimates, specifically the cytologic interpretation of baseline Pap smear, number of Pap smears during follow-up, age at enrollment, age at prediagnosis visit, and age at diagnosis. All statistical tests were two-sided. RESULTS: Oral contraceptive use and parity were not associated with risk of CIN3 or cervical cancer. Former smokers, women who smoked less than one pack of cigarettes per day, and women who smoked one or more packs per day had crude RRs for CIN3 or cervical cancer for the entire follow-up period of 2.1 (95% CI = 1.1 to 3.9), 2.2 (95% CI = 1.2 to 4.2), and 2.9 (95% CI = 1.5 to 5.6), respectively, compared with never smokers. In the multivariable model, former smokers, women who smoked less than one pack/day, and women who smoked one or more packs/day had RRs of 3.3 (95% CI = 1.6 to 6.7), 2.9 (95% CI = 1.4 to 6.1), and 4.3 (95% CI = 2.0 to 9.3), respectively, for CIN3 or cervical cancer compared with never smokers. CONCLUSIONS: Smoking is associated with an increased risk of invasive cervical cancer in women who are infected with oncogenic HPV. Subsequent studies should examine the role of smoking in the multistage pathogenesis of cervical cancer.     

Use of oral contraceptives and endometrial cancer risk (Sweden)

Objectives: To estimate the magnitude and persistence of the protective effect of use of combined oral contraceptives (COCs) and endometrial cancer risk.Methods: We performed a nation-wide, population-based case–control study among postmenopausal women aged 50–74 years in Sweden, which included 709 subjects with incident, histopathologically verified endometrial cancer, and 3,368 controls with an intact uterus. We used unconditional logistic regression to calculate odds ratios as estimates of relative risks.Results: Use of any sort of oral contraceptive decreased risk for endometrial cancer by 30%, while progestin-only pills reduced risk more markedly. For COCs the reduction in risk was noticeable following 3 or more years of use (OR 0.5, 95% CI 0.3–0.7), and increased with duration of intake, reaching 80% lower risk after 10 years of use. The protective effect of COC use was similar for all degrees of tumor differentiation and invasiveness, and remained for at least 20 years after cessation of use. Subsequent use of hormone replacement did not modify these protective effects.Conclusions: We conclude that COC use confers a long-lasting protection against endometrial cancer risk which is particularly marked for long-term users.(institution where the work has been performed)     

The dose-effect relationship between 'unopposed' oestrogens and endometrial mitotic rate: its central role in explaining and predicting endometrial cancer risk

The 'unopposed oestrogen hypothesis' for endometrial cancer maintains that risk is increased by exposure to endogenous or exogenous oestrogen that is not opposed simultaneously by a progestagen, and that this increased risk is due to the induced mitotic activity of the endometrial cells. Investigation of the mitotic rate during the menstrual cycle shows that increases in plasma oestrogen concentration above the relatively low levels of the early follicular phase do not produce any further increase in the mitotic rate of endometrial cells. A modification of the unopposed oestrogen hypothesis which includes this upper limit in the response of endometrial cells to oestrogen is consistent with the known dose-effect relationships between endometrial cancer risk and both oestrogen replacement therapy and postmenopausal obesity; it also suggests that the mechanism by which obesity increases risk in premenopausal women involves progesterone deficiency rather than oestrogen excess, and that the protective effect of cigarette smoking may be greater in postmenopausal than in premenopausal women. Detailed analysis of the age-incidence curve for endometrial cancer in the light of this hypothesis suggests that there will be lifelong effects of even short duration use of exogenous hormones. In particular, 5 years of combination-type oral contraceptive use is likely to reduce a woman's lifetime risk of endometrial cancer by some 60%; whereas 5 years of unopposed oestrogen replacement therapy is likely to increase her subsequent lifetime risk by at least 90%; and even 5 years of 'adequately' opposed therapy is likely to increase subsequent lifetime risk by at least 50%.     

Oral contraceptives and the risk of endometrial cancer

The relationship between the use of combbination oral contraceptives (OCs) and the risk of endometrial cancer was assessed in a case-control study conducted in the Swiss Canton of Vaud between 1 January 1988 and 31 July 1990. Subjects included 122 women aged 75 or less with histologically confirmed endometrial cancer, and 309 control women in hospital for acute conditions unrelated to OC use. Overall, 14 percent of cases and 27 percent of controls had ever used OCs, corresponding to a multivariate relative risk (RR) of 0.5 (95 percent confidence interval [CI]: 0.3. 0.8). The risk of endometrial cancer was found to be related inversely to duration of OC use: RR=1.0 for less than two years of OC use; 0.5 for two to five years; and 0.3 (95 percent CI: 0.1, 0.7) for more than five years. The protection appeared greater within 20 years since last use, and the RR rose to 0.8 after 20 or more years since last use; numbers are too small, however, for reliable inference from these subanalyses. No significant interaction or modifying effect was observed with other major factors related to endometrial cancer, including parity, body mass index, estrogen replacement therapy, and cigarette smoking. While this study provides further evidence for the protective effect of OCs against risk of endometrial cancer, the relationship requires continued evaluation to assess the long-term implications and public health impact of OC use.This work was supported in part by the Swiss National Science Foundation Grant No. 3.866-0.88.     

Risk Factors for Breast Cancer in Iranian Women Aged Less than 40 Years

This case-control study was carried out in a university-affiliated teaching hospital, Tehran city, Iran. A total of312 newly diagnosed cases aged less than 40 years old participated and were matched for age and ethnicity with312 controls. The results showed that in women who never married (OR=2.42 95%CI=1.51-3.88) (P<0.001), hada family history of breast cancer (OR=7.07 95%CI=2.95-16.99) (P<0.001), a low age of menarche (OR=0.1 95%CI=0.04-0.23) (P<0.001)), lower parity (OR=13.3 95% CI=3.89-45.66) (P<0.001) and took oral contraceptive pills(OR= 2.83 95% CI=1.87-4.24) (P<0.000) were at increased risk. A direct association with age at first birth wasalso evident(P=0.041), with a significantly inverse association between duration of lactation and breast cancer risk(p=0.016). On multivariate logistic regression, parity, family history of breast cancer, use of oral contraceptivepills, and age at first birth remained significant. In women lower than 40 years of age, breast cancer risk wassignificantly higher in women with parity ≥4 compared with nulliparity but no association emerged with historyof breast-feeding. Other risk factors were similar to those described in breast cancer epidemiology at any age.     

Timing of births and oral contraceptive use influences ovarian cancer risk

Increasing parity and duration of combined oral contraceptive (COC) use provide substantial protection against ovarian carcinoma (cancer). There are limited data on the impact of the age of the births or age of COC use on reducing ovarian cancer risk. Here, we examined the effects of age at first and last births and age at use of COCs using data from studies conducted in Los Angeles County, California, USA (1,632 cases, 2,340 controls). After adjusting for the number of births, every 5 years that a first birth was delayed reduced the risk of ovarian cancer by 13% (95% CI 5–21%; p = 0.003); a first birth after age 35 was associated with a 47% lower risk than a first birth before age 25. COC use before age 35 was associated with greater protection per year of use than COC use at older ages. Considering previously published results as well as the results presented here, increasing parity and a later age at births are both important protective factors against ovarian cancer and the protection extends over 30 or more years from last birth. Current models of the etiology of ovarian cancer do not encompass an effect of late age at births. Our result of an attenuation of the protective effect with COC use after around age 35 needs further investigation as it has not been seen in all studies.     

LHRH agonists and the prevention of breast and ovarian cancer

Early age at natural menopause or bilateral ovariectomy substantially reduce a woman's lifetime risk of breast cancer. Reversible 'bilateral ovariectomy' can now in effect be achieved by 'high-dose' luteinising hormone releasing hormone (LHRH) agonists (LHRHAs). The harmful effects of such medical reversible bilateral ovariectomy, in particular the increased risks of coronary heart disease and osteoporosis, can in all likelihood be obviated by 'low-dose' oestrogen replacement therapy (ERT), specifically 0.625 mg of conjugated equine oestrogens (CEE) for 21 days in each 28-day treatment cycle, and such ERT use will only negate to a relatively small extent the beneficial effect of such bilateral ovariectomy on breast cancer risk. We calculate that such an LHRHA plus low-dose ERT regimen given to a premenopausal woman for 10 years will, in addition to being a most effective contraceptive, decrease her lifetime risk of breast cancer by more than 50%. We calculate that such a 10-year regimen will also decrease her risk of ovarian cancer by two-thirds. This regimen should leave endometrial cancer risk and bone metabolism unaltered, and may reduce the risk of heart disease. The addition of a 'low-dose' progestogen to the regimen for 12 days in each 28-day treatment cycle would be beneficial to the endometrium, but it will adversely affect risk factors for heart disease and it may significantly reduce the benefit of the regimen as regards breast cancer. A satisfactory compromise may be to add a low-dose progestogen for 12 days at less frequent intervals. Another possibility may be to deliver a progestogen solely to the endometrium with an intra-uterine device; the benefits of such a regimen would be a significant reduction in the incidence of breast, ovarian and endometrial cancer.     

Endometrial cancer following treatment for breast cancer: a case-control study in Denmark

To evaluate the risk of endometrial cancer subsequent to breast cancer, a case-control study was carried out in Denmark. Between 1943-1977, 115 cases of histologically confirmed endometrial carcinoma developed more than 3 months after the diagnosis of a primary breast cancer in 51,638 women. A total of 235 breast cancer patients with no second primary cancer were matched to the cases on age, calendar year of diagnosis, and survival with an intact uterus. Identification of cases and controls relied upon records available in the Danish Cancer Registry. Information on risk factors and reproductive histories was abstracted from hospital records. Increased relative risks (RR) for endometrial cancer were associated with menopausal oestrogen use (RR = 4.9), nulliparity (RR = 2.1), late age at natural menopause (RR = 2.9), and pelvic irradiation (RR = 1.4). No association was apparent for drugs used to treat breast cancer. This study indicates that breast and endometrial cancer share several common aetiologic factors and that studies of second primary cancers have the potential to provide information on risk factors other than those associated with therapy.     

Oral contraceptives and risk of ovarian and breast cancers in BRCA mutation carriers: a meta-analysis

Prophylactic salpingo-oophorectomy is currently the only effective strategy available for decreasing ovarian cancer risk in BRCA1/2 mutation carriers. Significantly decreased risk of ovarian cancer associated with the use of combined oral contraceptives (COCs) was shown in the general population, which could be an alternative approach for those who do not accept risk-reducing surgery. Cohort, case-control and case-case studies published in English up to December 2009 reporting the association of ovarian or breast cancer risk with the use of COCs and presenting BRCA status were selected for meta-analysis. Meta-analysis of three case-control studies showed a significant risk reduction of ovarian cancer in BRCA1/2 mutation carriers who were associated with any past COC use (odds ratio [OR]: 0.57; 95% CI: 0.47-0.70; p < 0.001) and significant trend by duration of COC use (OR: 0.95; 95% CI: 0.93-0.97; p < 0.001). No significant increase in breast cancer risk associated with COC use has been found in case-control studies in BRCA1 (OR: 1.08; p = 0.250), in BRCA2 (OR: 1.03; p = 0.788) mutation carriers or in case-case studies in BRCA1/2 carriers (OR: 0.80; p = 0.147). Significantly increased risk of breast cancer was only shown on a subset of cohort studies in BRCA1 mutation carriers (OR: 1.48; 95% CI: 1.14-1.92). In conclusion, meta-analysis confirmed significantly decreased ovarian cancer risk in BRCA1/2 mutation carriers associated with the use of COCs comparable to the relative extent shown in the general population. Data on the risk of breast cancer associated with COC use in BRCA mutation carriers are heterogeneous and results are inconsistent. COCs can be considered as an alternative strategy in the chemoprevention of ovarian cancer in BRCA1 mutation carriers who do not accept prophylactic salpingo-oophorectomy above the age of 30 years.     

Does menopausal hormone replacement therapy interact with known factors to increase risk of breast cancer?

PURPOSE: We and other investigators have previously shown that postmenopausal combined estrogen and progestin replacement therapy (EPRT) increases the risk of breast cancer and that the risk associated with EPRT is substantially higher than for estrogen replacement therapy (ERT) alone. The present study was conducted to determine whether any particular subgroup of women are at particularly high risk of breast cancer if they use EPRT and whether tumor characteristics in women who develop cancer while on ERT or EPRT are different from those in women not using ERT or EPRT. PATIENTS AND METHODS: We conducted a population-based case-control study in Los Angeles, CA, with patients diagnosed with breast cancer in the late 1980s and early 1990s. Control subjects were matched to patients on age, ethnicity, and neighborhood of residence. We present data on 1,897 postmenopausal patients and 1,637 controls aged 55 to 72 years who had not undergone a simple hysterectomy. RESULTS: Relative risk of breast cancer associated with EPRT use did not vary with body mass index (body mass index at or below v above median [24.6 kg/m(2)]; P =.98), alcohol intake (> or + one v < one drink per week; P =.16), parity (nulliparous v parous; P =.45), history of benign breast disease (yes v no; P =.99), or family history of breast cancer (first degree v none; P =.57). All of these results were compatible with our previously reported estimate of an increased risk of breast cancer of 5% per year of use of EPRT. Hormone users, principally EPRT users, were more likely to have hormone receptor--positive, especially progesterone-positive, tumors. CONCLUSION: We found no evidence that the risk of breast cancer associated with EPRT is limited to subgroups of women with specific cofactors. Tumors in EPRT users are more often hormone receptor--positive, indicating that they may have a better prognosis than breast cancer overall.     

Oral contraceptive use and the risk of ovarian cancer: An Italian case-control study

The association between oral contraceptive (OC) use and the risk of ovarian cancer was analysed in a case-control study, conducted between 1985 and 1989 on 505 epithelial ovarian cancer cases under 60 years of age, and 1375 controls in hospitals for a spectrum of acute conditions, not gynaecological, hormonal or neoplastic, apparently unrelated to OC use. 41 (8.1%) women with epithelial ovarian cancer and 192 (14.0%) controls reported OC use. The multivariate relative risk (RR) for ever use was 0.7 (95% confidence interval (CI) = 0.5–1.0). The risk decreased with duration of use: compared with never users the multivariate RRs were 0.9 and 0.5 respectively for less than 2 years and 2 years or more users (X²₁ trend = 6.17, P = 0.01). The risk of ovarian cancer decreased with recency and latency of use: the estimated RR were 0.5 and 0.9 in women reporting last OC use less than 10 or 10 years or more from the diagnosis of the disease, and 0.6 and 0.8 in those reporting first OC use less than 10 or 15 or more years before. The protective effect of OC was consistent in separate strata of selected covariates, including parity and other major known or suspected risk factors for ovarian cancer. There was some indication that the protection declines with advancing age, but the risk estimates were similar in premenopause and postmenopause.     

Use of electric blankets and association with prevalence of endometrial cancer.

The objective of this study was to assess the relationship between electric blanket use and prevalence of endometrial cancer for women. Information relating to women enrolled in the Women's Health Initiative Observational Data Set (n=93 676) used to test the relationship factors associated with endometrial cancer included older age at screening, younger age at last menstrual period, region of domicile (highest prevalence in the South), less than a high school education, lower income, body mass index >25 kg/m, low parity, unopposed use of estrogen, never use of estrogen plus progesterone, past alcohol use, higher percentage of daily calories from fat and any electric blanket use. Following a univariate identification of factors significantly related to endometrial cancer, stepwise logistic regression analysis was performed for those factors with P values of less than 0.001 in the univariate analysis. Using electric blankets was associated with a 15% higher prevalence of endometrial cancer than never having used electric blankets (odds ratio=1.15, 95% confidence interval: 1.03-1.27). After controlling for variables significantly associated with endometrial cancer, use of electric blankets for 20 years or more was associated with 36% higher prevalence of endometrial cancer (odds ratio=1.36, 95% confidence interval: 1.16-1.59). Although we were unable to determine the duration of electric blanket use before diagnosis of endometrial cancer, we found that women using electric blankets for 20 years or more had a significantly higher prevalence.     

Hormone replacement therapy and risk of epithelial ovarian cancer.

It has been suggested that oestrogen replacement therapy is associated with risk of epithelial ovarian cancer of the endometrioid type. Using data from an Australian population-based case-control study, the relation between unopposed oestrogen replacement therapy and epithelial ovarian cancer, both overall and according to histological type, was examined. A total of 793 eligible incident cases of epithelial ovarian cancer diagnosed from 1990 to 1993 among women living in Queensland, New South Wales and Victoria were identified. These were compared with 855 eligible female controls selected at random from the electoral roll, stratified by age and geographic region. Trained interviewers administered standard questionnaires to obtain detailed reproductive and contraceptive histories, as well as details about hormone replacement therapy and pelvic operations. No clear associations were observed between use of hormone replacement therapy overall and risk of ovarian cancer. Unopposed oestrogen replacement therapy was, however, associated with a significant increase in risk of endometrioid or clear cell epithelial ovarian tumours (odds ratio (OR) 2.56; 95% confidence interval (CI) 1.32-4.94). In addition, the risk associated with oestrogen replacement therapy was much larger in women with an intact genital tract (OR 3.00; 95% CI 1.54-5.85) than in those with a history of either hysterectomy or tubal ligation. Post-menopausal oestrogen replacement therapy may, therefore, be a risk factor associated with endometrioid and clear cell tumours in particular. Additionally, the risk may be increased predominantly in women with an intact genital tract. These associations could reflect a possible role of endometriosis in the development of endometrioid or clear cell ovarian tumours.     

A cohort study of reproductive and hormonal factors and renal cell cancer risk in women

We examined the association of reproductive and hormonal factors with renal cell cancer risk in a cohort study of 89 835 Canadian women. Compared with nulliparous women, parous women were at increased risk (hazard ratio (HR) 1.78, 95% confidence interval (CI) 1.02-3.09), and there was a significant gradient of risk with increasing levels of parity: relative to nulliparous women, women who had > or =5 pregnancies lasting 4 months or more had a 2.4-fold risk (HR=2.41, 95% CI=1.27-4.59, P for trend 0.01). Ever use of oral contraceptives was associated with a modest reduction in risk. No associations were observed for age at first live birth or use of hormone replacement therapy. The present study provides evidence that high parity may be associated with increased risk of renal cell cancer, and that oral contraceptive use may be associated with reduced risk.     

Risk factors for endometrial cancer at different ages

The importance of the major risk factors for endometrial cancer in women of different ages was evaluated with the use of data from a hospital-based case-control study conducted in Milan, Italy, on 283 women with endometrial cancer and 566 age-matched controls. Current weight was related strongly to the risk of endometrial cancer both in younger (premenopausal) and in older women (with risk estimates for the heaviest categories of 20.3 and 7.7, respectively), thus confirming that obesity is the major cause of endometrial cancer in Northern Italy. Endometrial cancer risk appeared to be approximately proportional to the second power of body mass index. Early menarche and nulliparity were associated with an increased risk of endometrial cancer in premenopausal women, the point estimate for nulliparity rising to 35.1 (with lower confidence limit of 10.2) after adjustment for marital status. However, no association with these factors was evident in postmenopausal women. Combination oral contraceptives were used by 2 cases and 19 controls only [relative risk (RR) = 0.2, with 95% confidence interval = 0.1-0.8]. The use of noncontraceptive estrogens was associated with an elevated risk, which was greater in perimenopausal women (RR = 5.1 for greater than 2 yr of use), and decreased progressively with increasing time after menopause. Late menopause was also related to endometrial cancer. However, the risk estimates for late menopause apparently were more elevated in older women (greater than or equal to 65 yr) than in perimenopausal women. Most of the risk factors identified (excluding late menopause) apparently act on one of the later stages of the process of carcinogenesis, because the excess risk drops after cessation of exposure.