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.     

Oral contraceptive use and mammographic patterns.

High-risk mammographic patterns represent an increased risk of contracting breast cancer and may be used as a surrogate endpoint for the disease. We examined the relationship between oral contraceptive (OC) use and mammographic patterns among 3218 Norwegian women, aged 40-56 years. Information on ever OC use, duration, and age of first OC use and other epidemiological data were obtained through questionnaires. The mammograms were categorized into five groups. Patterns I-III were combined into a low-risk group and patterns IV and V into a high-risk group. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression and adjusted for age, menopausal status, parity, age at first birth, and body mass index. Women who reported ever having used OCs were 20% more likely (OR 1.27, 95% CI 1.0-1.6) to have high-risk mammographic patterns compared with those reporting never having used OCs. There was no dose response between different measures of OC use and high-risk patterns. Among nulliparous women, ever OC users were four times more likely (OR 4.65, 95% CI 2.1-10.3) to have high-risk patterns compared with never users. Our findings suggest that, especially among nulliparous women, ever OC use may exert its effect on breast cancer risk through changes in breast tissue, which can be observed on a mammogram.     

Impact of teenage oral contraceptive use in a population-based series of early-onset breast cancer cases who have undergone BRCA mutation testing

Oral contraceptive (OC) use in young women has been associated with an increased risk of breast cancer. This matched case-control study aims to elucidate the combined effects of OC use and genetic factors in a population-based series of BRCA1/2 mutation-tested early-onset breast cancers. A first invasive breast cancer was diagnosed in 259 women aged 40 years between 1990 and 1995 in the South Swedish Health Care Region. A total of 245 women were included in this study. Information on family history of cancer, reproductive factors, smoking and OC use was obtained from questionnaires or patient charts. Three age-matched controls per case were chosen from a prospective South Swedish cohort. Ever OC use and current OC use were not associated with breast cancer. Cases were more likely to have used OCs before age 20 years (adjusted odds ratio (OR) 2.10 (95% CI 1.32-3.33)) and before their first child (adjusted OR 1.63 (95% CI 1.02-2.62)). When stratified by age, the effect of early OC use was limited to women diagnosed prior to age 36 years (OR 1.53 (1.17-1.99) per year of OC use prior to age 20 years). The risks were similar for low-dose and high-dose OCs. The probability of being a BRCA1/2 mutation carrier was three times higher among cases who started OC use prior to age 20 years compared with cases who started at age 20 years or older or who had never used OCs. However, the duration of OC use was similar among cases with and without BRCA1/2 mutations. No association was seen with a first-degree family history of breast cancer. Each year of OC use prior to age 20 years conferred a significantly increased risk for early-onset breast cancer, while there was no risk associated with use after age 20 years.     

Intrauterine device use and risk of endometrial cancer.

The relationship between intrauterine device (IUD) use and risk of endometrial cancer has been analysed in a case-control study conducted in Italy between 1983 and 1992, including 453 patients with histologically confirmed endometrial cancer and 1,451 controls admitted for acute, non-gynaecological, non-hormonal, non-neoplastic conditions to the same network of hospitals where cases had been identified. Two (0.4%) cases versus 36 (2.3%) controls reported ever using an IUD. The corresponding multivariate relative risk was 0.4 (95% CI 0.1-1.0). The results of this study and the few published available epidemiological data suggest a protective role of IUD use on endometrial carcinogenesis, but potential selective mechanisms for IUD utilisation (indication bias) should be carefully considered in the interpretation.     

Oral contraceptive use and breast cancer risk: modification by NAD(P)H:quinone oxoreductase (NQO1) genetic polymorphisms.

Despite intensive study, the relationship between oral contraception (OC) and breast cancer remains unclear. OCs contain a potent synthetic estrogen (ethinyl estradiol) but lower endogenous estradiol levels, and ethinyl estradiol is a weak progenitor of semiquinones, catechol estrogens capable of damaging DNA. NAD(P)H:quinone oxoreductase (NQO1) stabilizes semiquinones, thus potentially preventing genetic damage from catechol estrogens, and the NQO1 C609T polymorphism seems functionally relevant. Using data from the Shanghai Breast Cancer Study, a population-based case-control study, we investigated the relationships between OC use (20% ever using), breast cancer, and NQO1 (C/C 31% and C/T + T/T 69%) among 1,039 cases and 1,121 controls. Breast cancer was not significantly associated with NQO1 genotype. There was a significant protective association between OC after age 30 years and premenopausal breast cancer [odds ratio (OR) 0.51, 95% confidence interval (95% CI) 0.29-0.89] primarily with the NQO1 T allele (C/C OR 0.76, 95% CI 0.31-1.82; C/T + T/T OR 0.38, 95% CI 0.18-0.80; P for interaction = 0.19). The association between premenopausal breast cancer and OCs significantly differed with NQO1 genotype when using OCs for >18 months (C/C OR 2.34, 95% CI 0.92-5.99; C/T + T/T OR 0.69, 95% CI 0.38-1.25; P for interaction = 0.02). Among women with the C/C genotype, postmenopausal breast cancer was significantly associated with ever-using OCs (C/C OR 2.01, 95% CI 1.08-3.74; C/T + T/T OR 0.72, 95% CI 0.49-1.05; P for interaction < 0.01). This crossover was stronger with OC use prior to age 30 years (C/C OR 3.00, 95% CI 1.43-6.25; C/T or T/T OR 0.49, 95% CI 0.29-0.81; P for interaction < 0.01). Our results require confirmation but suggest that the OC and breast cancer association depends on the ability to invoke protection from catechol estrogens.     

Long-term effects of oral contraceptives on ovarian cancer risk

Several epidemiologic studies have reported a protective effect of oral contraceptives (OCs) on ovarian cancer. However, there remain open issues, including better quantification of time-related factors such as time since last use, age at first use and time since first use. We performed a collaborative reanalysis of 6 case-control studies conducted between 1978 and 1999 in the United Kingdom, Greece and Italy, including a total of 2,768 incident, histologically confirmed cases of epithelial ovarian cancer and 6,274 hospital controls under age 70 years. A reduced risk of ovarian cancer was found for ever- compared to never-users [odds ratio (OR) = 0.66, 95% confidence interval (CI) 0.56-0.79], and a stronger reduction was observed for women who had used OCs for > or =5 years (OR = 0.50, 95% CI 0.33-0.76) compared to those who had used them for <5 years. The protective effect of OCs on ovarian cancer was consistent across strata of age, parity, menopausal status and family history of breast or ovarian cancer. After allowance for duration of use, no other time factor was related to ovarian cancer risk: the reduced risk was similar for women who stopped OC use > or =20 years before compared to <10 years; likewise, no significant modification of risk reduction was observed for age at first OC use and time since first OC use. The present analysis indicates that, after taking into account duration of OC use, the OC protection from ovarian cancer persists for a long time after stopping use.     

Oral contraceptives, hormone replacement therapy and the risk of colorectal cancer.

The relationship between oral contraceptives (OCs), menopausal hormone replacement therapy (HRT) and the risk of colorectal cancer was investigated in a case-control study conducted in northern Italy between 1985 and 1992 on 709 women with incident colorectal cancer and 992 controls admitted to hospital for a wide spectrum of acute, non-neoplastic, non-digestive tract, non-hormone-related disorders. A reduced risk of colorectal cancer was observed in women who had ever used OCs [multivariate odds ratio (OR) = 0.58; 95% confidence interval (CI): 0.36-0.92]. The OR was 0.52 (95% CI 0.27-1.02) for use over 2 years. For women ever using HRT, the multivariate OR was 0.40 (95% CI 0.25-0.66). The risk was inversely related to duration of use, with ORs of 0.46 for 2 years or less and 0.25 for more than 2 years of use. No consistent pattern of trends was observed with time since first or last use. This study provides further evidence that OC and HRT do not increase, and possibly decrease, the risk of colorectal cancer. These results, if confirmed, would have important implications for the ultimate risk-benefit assessment of female hormone preparations.     

Oral contraceptives and cervical cancer--further findings from the Oxford Family Planning Association contraceptive study.

In 1983, we reported results from the Oxford Family Planning Association contraceptive study regarding the association between oral contraceptives (OCs) and cervical neoplasia, after a 10 year follow-up of a cohort of 17,000 women. Further findings from this study are reported here after an additional 12 years of follow-up. A nested case--control design was used in which cases were all women diagnosed under 45 years of age with invasive carcinoma (n = 33), carcinoma in situ (n = 121) or dysplasia (n = 159). Controls were randomly selected from among cohort members and matched to cases on exact year of birth and clinic attended at recruitment to study. Conditional logistic regression analysis was used to determine odds ratios (ORs) and 95% confidence intervals (CIs) associated with various aspects of OC use relative to never users adjusted for social class, smoking, age at first birth and ever use of diaphragm or condom. Ever users of OCs had a slightly elevated OR for all types of cervical neoplasia combined (OR = 1.40, 95% CI 1.00-1.96). Odds ratios were highest for invasive carcinoma (OR = 4.44, 95% CI 1.04-31.6), intermediate for carcinoma in situ (OR = 1.73, 95% CI 1.00-3.00) and lowest for dysplasia (OR = 1.07, 95% CI 0.69-1.66). The elevated risk associated with OC use appeared to be largely confined to current or recent (last use in the past 2 years) long-term users of OCs. Among current or recent users, ORs for all types of cervical neoplasia combined were 3.34 (95% CI 1.96-5.67) for 49-72 months of use, 1.69 (95% CI 0.97-2.95) for 73-96 months and 2.04 (95% CI 1.34-3.11) for 97 or more months. These results suggest a possible effect of OC use on later stages of cervical carcinogenesis, although residual confounding due to sexual factors or human papillomavirus (HPV) infection cannot be ruled out.     

A pooled analysis of case-control studies of thyroid cancer¶ III. Oral contraceptives, menopausal replacement therapy and other female hormones

Objective: The relations between oral contraceptives (OC), hormone replacement therapy (HRT) for menopause, and other female hormone use and thyroid cancer risk was analyzed using the original data from 13 studies from North America, Asia and Europe.Methods: Based on 2,132 cases and 3,301 controls, odds ratios (OR) and the corresponding 95% confidence intervals (CI) were obtained by conditional regression models, conditioning on study and age at diagnosis, and adjusting for age, radiation exposure and parity.Results: Overall, 808 (38%) cases versus 1,290 (39%) controls had ever used OCs, corresponding to an OR of 1.2 (95% CI 1.0 to 1.4). There was no relation with duration of use, age at first use, or use before first birth. The OR was significantly increased for current OC users (OR=1.5, 95% 1.0 to 2.1), but declined with increasing time since stopping (OR=1.1 for >10 years since stopping). The association was stronger for papillary cancers (OR=1.6 for current users) than for other histologic types. No significant heterogeneity was observed across studies or geographic areas. Eight studies had data on HRT, for a total of 1,305 cases and 2,300 controls: 110 (8%) cases and 205 (9%) controls reported ever using HRT (OR=0.8; 95% CI 0.6 to 1.1). The ORs were 1.6 (95% to 0.9 to 2.9) for use of fertility drugs, and 1.5 (95% CI 1.1 to 2.1) for lactation suppression treatment.Conclusions: The studies considered in these analyses include most of the epidemiological data on the role of exogenous hormone use in the etiology of thyroid cancer, and they provide reassuring evidence on the absence of an association of practical relevance. The moderate excess risk in current OC users, if not due to increased surveillance for thyroid masses among OC users, is similar to that described for breast cancer, and would imply a role of female hormones on thyroid cancer promotion. There was no indication of increased thyroid cancer risk 10 or more years after discontinuing OC use.     

Oral contraceptive use and cancer. Findings in a large cohort study, 1968-2004

We examined cancer incidence in relation to oral contraceptive (OC) use in the Oxford Family Planning Association contraceptive study. The study includes 17032 women, recruited at family planning clinics at ages 25-39 years between 1968 and 1974, who were using OCs, a diaphragm, or an intrauterine device. Follow-up data were available until 2004. OC use was not significantly related to nonreproductive cancer. Breast cancer findings (844 cases) likewise were very reassuring (rate ratio (RR) comparing women ever using OCs with those never doing so 1.0, 95% confidence interval (CI) 0.8-1.1). There was a strong positive relationship between cervical cancer incidence (59 cases) and duration of OC use (RR comparing users for 97+ months with nonusers 6.1, 95%CI, 2.5-17.9). Uterine body cancer (77 cases) and ovarian cancer (106 cases) showed strong negative associations with duration of OC use: RRs for 97+ months of use were 0.1 (95%CI, 0.0-0.4) and 0.3 (95%CI, 0.1-0.5) respectively. This apparent protective effect for both cancers persisted more than 20 years after stopping OCs. Combining data for cancers of the cervix, uterine body and ovary, the age adjusted RR for women ever using OCs compared with those never doing so was 0.7 (95%CI, 0.5-0.8). Beneficial effects of OCs on the gynaecological cancers thus outweighed adverse effects.     

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.     

Intra-uterine contraception and the risk of endometrial cancer

Despite the increasing world-wide popularity of contraceptive intra-uterine devices (IUDs), their potential long-term effects on the risk of developing endometrial carcinoma have been poorly studied. This paper reports on the relationship between intra-uterine contraception and endometrial cancer by analyzing epidemiological data from a large, multicenter, population-based, case-control study of epithelial endometrial cancer. Cases were 437 women, 20 to 54 years of age, with histologically confirmed epithelial endometrial cancer ascertained through 6 population-based cancer registries in the United States. Controls were 3200 women selected at random from the populations of these areas. The age- and parity-adjusted odds ratio (OR) for the association between ever having used intra-uterine contraception and endometrial cancer was 0.51 (95% confidence interval (Cl) 0.3–0.8). Although the protective effect increased with duration of use, a dose-response relationship among users was not statistically demonstrable. The association did not vary significantly with age at first or last IUD use or with time elapsed since first or last IUD use. Years of education significantly modified the effect of intra-uterine contraception. Thus, intra-uterine contraception appeared to be strongly protective for women with at least 13 years of education (OR = 0.29, 95% Cl, 0.15–0.6). It is proposed that intra-uterine contraception exerts its protective effect through local structural and biochemical changes in the endome-trium that may alter endometrial sensitivity and response to circulating estrogen and progesterone.     

Reproductive factors, oral contraceptive use, and human papillomavirus infection: pooled analysis of the IARC HPV prevalence surveys.

High parity, early age at first full-term pregnancy (FTP), and long-term oral contraceptive (OC) use increase cervical cancer risk, but it is unclear whether these variables are also associated with increased risk of acquisition and persistence of human papillomavirus (HPV) infection, the main cause of cervical cancer. Information on reproductive and menstrual characteristics and OC use were collected from 14 areas worldwide, among population-based, age-stratified random samples of women aged 15 years or older. HPV testing was done using PCR-based enzyme immunoassay. Unconditional logistic regression was used to estimate the odds ratios (OR) of being HPV-positive according to reproductive and menstrual factors and corresponding 95% confidence intervals (CI). When more than two groups were compared, floating CIs (FCI) were estimated. A total of 15,145 women (mean age, 40.9 years) were analyzed. Women with >or=5 FTPs (OR, 0.90; 95% FCI, 0.76-1.06) showed a similar risk of being HPV-positive compared with women with only one FTP (OR, 1.00; 95% FCI, 0.86-1.16). However, nulliparous women showed an OR of 1.40 (95% CI, 1.16-1.69) compared with parous women. Early age at first FTP was not significantly related to HPV positivity. HPV positivity was similar for women who reported >or=10 years of use of OCs (OR, 1.16; 95% FCI, 0.85-1.58) and never users of OCs (OR, 1.00; 95% FCI, 0.90-1.12). Our study suggests, therefore, that high parity, early age at first FTP, and long-term OC use are not associated with HPV prevalence, but rather these factors might be involved in the transition from HPV infection to neoplastic cervical lesions.     

Use of oral contraceptives,intrauterine devices and tubal sterilization and cancer risk in a large prospective study,from 1996 to 2006

The association of contraceptive methods, including oral contraceptives (OC), intrauterine devices (IUD) and tubal sterilization (TS), with overall and site‐specific cancer were prospectively investigated in a cohort of 66,661 Chinese women in Shanghai, 76.7% of whom used contraception. During a median follow‐up time of 7.5 years, 2,250 women were diagnosed with cancer. Ever‐use of any contraceptive method was not associated with overall cancer risk [adjusted hazard ratio (HR_adj) = 1.02, 95% CI, 0.92–1.12]. Use of any contraceptive method was associated with increased risk of rectal cancer (HR_adj = 1.68, 95% CI, 1.08–2.62) and reduced risk of thyroid cancer (HR_adj = 0.63, 95% CI, 0.38–1.04). Risk of gallbladder cancer increased with ever use of OC (HR_adj = 2.38, 95% CI, 1.26–4.49). IUD use was associated with a possible reduced risk of thyroid cancer (HR_adj = 0.64, 95% CI, 0.38–1.07). Longer duration of IUD use decreased risk for breast, thyroid and lung cancers. Ever having a TS was associated with increased uterine body cancer (HR_adj = 2.50, 95% CI, 1.47–4.25) and decreased risk of stomach cancer (HR_adj = 0.59, 95% CI, 0.39–0.91). We did not find any contraceptive method to be related to the risk of ovarian cancer but the analyses were based on few events. Although chance findings are a likely explanation for some of the associations found in our study, these findings suggest that various contraceptive methods or reproductive patterns may play a role in the etiology of cancer. © 2008 Wiley‐Liss, Inc.     

Tamoxifen and toremifene treatment of breast cancer and risk of subsequent endometrial cancer: a population-based case-control study

A population-based case-control study was performed to evaluate the risk of endometrial cancer related to tamoxifen or toremifene treatment. All patients with breast cancer diagnosis since 1980 in Finland who subsequently developed an endometrial cancer by the end of 1995 and 3 matched controls were identified among the 38,000 breast cancer patients of the Finnish Cancer Registry database. Detailed information on treatment of breast cancer and potential confounders was collected from hospital records. The OR for tamoxifen treatment (59 cases), adjusted for significant cofactors (increased risk associated with obesity, low parity and PR positivity) was 2.9 (95% CI 1.8-4.7). The OR for toremifene (3 cases) was 0.9 (95% CI 0.3-3.9). The OR related to adjuvant tamoxifen treatment reached its maximum 2-5 years after the beginning of treatment (OR 5.1, 95% CI 2.1-13), while the OR for tamoxifen used for palliative treatment of advanced breast cancer was especially high after a lag of over 5 years (OR 9.5, 95% CI 2.5-36). The risk increase due to tamoxifen was slightly higher if the age at initiation was below 55, and risk was more pronounced among patients with well-differentiated endometrial cancer than patients with cancers of clinical grades 2 or 3. According to our results, treatment with tamoxifen increases the risk of endometrial cancer. Due to the rare use of toremifene up to the mid-1990s, the risk assessment concerning it was inconclusive.     

Impact of progestin and estrogen potency in oral contraceptives on ovarian cancer risk.

BACKGROUND: Oral contraceptive (OC) use is associated with a reduced risk of developing ovarian cancer, but the mechanism for the risk reduction has not been well defined. In this study, we investigate the relationship between the progestin and estrogen potency in combination OCs and the risk of developing ovarian cancer. METHODS: The study included 390 case subjects with epithelial ovarian cancer and 2865 control subjects, between 20 and 54 years of age, identified from the Cancer and Steroid Hormone Study. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between ovarian cancer risk and combination OC formulations while controlling for potential confounders. All statistical tests were two-sided. RESULTS: With users of high-progestin/high-estrogen potency OC as the referent group, users of low-progestin/high-estrogen potency formulations (adjusted OR = 2.1; 95% CI = 1.2 to 3.7) and low-progestin/low-estrogen potency formulations (adjusted OR = 1.6; 95% CI = 0.9 to 3.0) had a higher risk of ovarian cancer than users of high-progestin/high-estrogen potency formulation. Low-progestin potency OC formulations were associated with a statistically significant higher risk than high-progestin potency formulations (adjusted OR = 2.2; 95% CI = 1.3 to 3.9). This association was seen even among users of short duration. CONCLUSION: The combination OC formulations with high-progestin potency appear to be associated with a greater reduction in ovarian cancer risk than those with low-progestin potency. Mechanisms underlying this reduction may include inhibition of ovulation and/or some direct biologic effects of the progestin.     

Oral, injected and implanted contraceptives and breast cancer risk among U.S. Hispanic and non-Hispanic white women

Associations between oral contraceptive (OC) use and breast cancer have been reported, but few studies have considered associations in racial and ethnic minorities. Data regarding injected or implanted hormonal contraceptives are limited. In a case-control study of Hispanic (796 cases, 919 controls) and non-Hispanic white (1,522 cases, 1,596 controls) women in the U.S. southwest interviewed in 2000-2005, 49% of Hispanic controls and 66% of non-Hispanic white controls reported having used OC. Breast cancer odds ratios (OR) associated with OC use within the past 5 years were 1.22 (95% confidence interval (CI) 0.80, 1.84) among Hispanics, 1.28 (95% CI 0.93, 1.76) among non-Hispanic whites, 1.27 (95% CI 0.99, 1.63) for both ethnic groups combined and 1.53 (95% CI 0.98, 2.40) for estrogen receptor (ER) negative tumors. OC use for 20 years or longer was associated with ORs of 1.50 (95% CI 1.04, 2.17) for both ethnic groups combined, and 2.23 (95% CI 1.17, 4.25) for ER negative tumors. Hormonal contraceptive injections were used by 3.3% of Hispanic controls and 2.8% of non-Hispanic white controls, OR 1.23 (95% CI 0.88, 1.73). Fifteen cases and 2 controls reported use of a subdermal contraceptive implant, OR 8.59 (95% CI 1.92, 38.39). Associations between OC use and breast cancer in Hispanics are consistent with modestly increased risk among recent users and for ER negative tumors, as observed in other populations. Based on a small number of users of contraceptive implants, a significantly increased breast cancer risk was observed; continued surveillance of implant users may be warranted.     

Oral contraceptives and breast cancer in northern Italy. Final report from a case-control study.

To assess the relation between oral contraceptive (OC) use and breast cancer, we analysed data from a case-control study conducted in Northern Italy between 1983 and 1991 on 2,309 cases below age 60 and 1,928 controls admitted to hospital for acute diseases unrelated to OC use and to any of the known or potential risk factors for breast cancer. OC use was reported by 16% of cases and 14% of controls. The multivariate relative risk (RR) for ever vs never use of combination OC was 1.2 (95% confidence interval (CI) 1.0-1.4). However, there was no trend in risk with duration. The RR was elevated for very short use, but declined to 0.8 (95% CI = 0.5-1.0) for five or more years'' use. No noteworthy relationship was found for other major measures of OC use, although RR estimates were above unity for women who had stopped use less than 5 years before (RR = 1.5, 95% CI = 1.1-2.0), started use less than 10 years before (RR = 1.3, 95% CI = 1.0-1.9), started when 25 or more years old (RR = 1.4, 95% CI = 1.1-1.7), or after first birth (RR = 1.2, 95% CI = 1.0-1.5). No interaction was observed between OC use and family history of breast cancer, parity and age at first birth. A separate analysis of 373 cases and 456 control below age 40 showed no association with ever use (RR = 0.9, 95% CI = 0.6-1.2).     

A prospective cohort study of oral contraceptive use and ovarian cancer among women in the United States born from 1947 to 1964

Purpose

Oral contraceptives (OCs) have been consistently associated with a reduced ovarian cancer risk; however, most previous studies included women in older birth cohorts using high-dose OC formulations. We assessed OC use, including type and dose, and ovarian cancer risk among women born between 1947 and 1964 using more recent formulations.

Methods

We included 110,929 Nurses’ Health Study II participants. Women reported duration of OC use and brands used from age 13 to baseline (1989) and every 2 years thereafter through 2009. We categorized brands by estrogen and progestin type, dose, and potency, and used Cox proportional hazards models, adjusted for age, calendar time, reproductive factors, and body mass index, to assess associations with ovarian cancer.

Results

Over 2,178,679 person-years of follow-up, we confirmed 281 cases. At baseline, 83% of participants reported ever using OCs. Compared to never use, we observed an increased risk of ovarian cancer with ≤6 months of OC use (HR 1.82; 95% CI 1.13–2.93) but a non-significant 57% (95% CI 0.18–1.03) decreased risk with ≥15 years of OC use. The increased risk among short-term users (≤1 year) was restricted to OCs containing mestranol (HR 1.83; 95% CI 1.16–2.88) and first-generation progestin (HR 1.72; 95% CI 1.11–2.65).

Conclusion

The associations between OCs and ovarian cancer observed for this younger birth cohort differ substantially from the results of previous cohort studies, possibly reflecting changes in OC formulations and use patterns over time, although these results could be due to chance. Additional studies should evaluate newer OC formulations and ovarian cancer risk.

     

Cytochrome P450 1B1 and catechol-O-methyltransferase polymorphisms and endometrial cancer susceptibility

Estrogen production and metabolism play critical roles in the development and pathogenesis of endometrial carcinoma. Cytochrome P450 1B1 (CYP1B1) and catechol-O-methyltransferase (COMT) are two key enzymes in the estrogen metabolism pathway that result in the hydroxylation and conjugation of estradiol, respectively. We evaluated the association between the CYP1B1 Leu432Val and CYP1B1 Asn453Ser polymorphisms and the COMT Val158Met polymorphism and invasive endometrial cancer risk in a case-control study nested within the Nurses' Health Study (n = 222 cases, 666 controls). We also evaluated whether body mass index (BMI), postmenopausal hormone (PMH) use and cigarette smoking modified the associations of the CYP1B1 and COMT genotypes and endometrial cancer risk. Conditional logistic regression was used 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 subjects who were homozygous for the wild-type allele. Carriers of the CYP1B1 Ser allele had a statistically significant decreased risk of endometrial cancer (OR = 0.62; 95% CI, 0.42-0.91); there was no significant association between the CYP1B1 Val allele and endometrial cancer risk (OR = 1.10; 95% CI, 0.75-1.59). Compared with the COMT Val/Val wildtype genotype, the adjusted OR of endometrial cancer for women with the COMT Val/Met or COMT Met/Met genotype was 0.96 (95% CI, 0.65-1.43). We did not observe any effect modification by BMI, PMH use and cigarette smoking for the CYP1B1 and COMT genotypes. Our data suggest, that the CYP1B1 Ser allele may decrease endometrial cancer risk by altering the production of catechol estrogens. However, further studies are warranted to elucidate the role of CYP1B1 in endometrial cancer.