Oral contraceptive use, hormone replacement therapy, reproductive history and risk of colorectal cancer in women

Evidence from epidemiologic studies suggests a possible role of exogenous and endogenous hormones in colorectal carcinogenesis in women. However, with respect to exogenous hormones, in contrast to hormone replacement therapy, few cohort studies have examined oral contraceptive use in relation to colorectal cancer risk. We used data from a large cohort study of Canadian women enrolled in a randomized controlled trial of breast cancer screening to assess the association of oral contraceptive use, hormone replacement therapy and reproductive factors with risk of colorectal cancer, overall and by subsite within the colorectum. Cancer incidence and mortality were ascertained by linkage to national databases. Among 89,835 women aged 40-59 at enrollment and followed for an average of 16.4 years, we identified 1,142 incident colorectal cancer cases. Proportional hazards models were used to estimate the associations between the exposures of interest and risk of colorectal cancer. Ever use of oral contraceptives at baseline was associated with a modest reduction in the risk of colorectal cancer (hazard ratio 0.83, 95% confidence interval 0.73-0.94), with similar effects for different subsites within the colorectum. No trend was seen in the hazard ratios with increasing duration of oral contraceptive use. No associations were seen with use of hormone replacement therapy (ever use or duration of use) or reproductive factors. Our results are suggestive of an inverse association between oral contraceptive use and colorectal carcinogenesis. However, given the lack of a dose-response relationship and the potential for confounding, studies with more complete assessment of exogenous hormone use throughout the life course are needed to clarify this association.     

Oral contraceptives and colorectal cancer risk: a meta-analysis

Several studies have suggested an inverse association between use of combined oral contraceptives (OC) and the risk of colorectal cancer and here we present a meta-analysis of published studies. Articles considered were epidemiological studies published as full papers in English up to June 2000 that included quantitative information on OC use. The pooled relative risks (RR) of colorectal cancer for ever OC use from the 8 case-control studies was 0.81 (95% confidence interval (CI): 0.69-0.94), and the pooled estimate from the 4 cohort studies was 0.84 (95% CI: 0.72-0.97). The pooled estimate from all studies combined was 0.82 (95% CI: 0.74-0.92), without apparent heterogeneity. Duration of use was not associated with a decrease in risk, but there was some indication that the apparent protection was stronger for women who had used OCs more recently (RR = 0.46; 95% CI: 0.30-0.71). A better understanding of this potential relation may help informed choice of contraception.     

Sunlight,hormone replacement status and colorectal cancer risk in postmenopausal women

A reanalysis of the Women's Health Initiative (WHI) randomized clinical trial found a significant interaction between supplementation with vitamin D/calcium and estrogen therapy and the risk of colorectal cancer risk, with reduced risks from supplementation limited to the placebo arms of the estrogen trials. To explore whether the vitamin D effects are modified by estrogen therapy, we report a largely cross‐sectional, analysis of the association between sun exposure, which is an important vitamin D source, and colorectal cancer risk among postmenopausal women in the U.S. Radiologic Technologists study. Among 21,695 participants, there were a total of 108 cases. Sun exposure was based on time outdoors and on ambient ultraviolet radiation (UV) exposure based on residence linked to erythemal exposures derived from the Total Ozone Mapping Spectrometer database. Although there was no relationship between outdoor time or ambient UV measure and colorectal cancer risk in current hormone replacement therapy (HRT) users, in never/past HRT users, there was an inverse association with higher ambient UV exposure, RR for highest vs. lowest tertile = 0.40; 95% CI 017, 0.93; p for trend = 0.04. Non‐significant lower risks were also associated with higher levels of outdoor time (≥3.5 hr/week) in never/past HRT users. The interaction between both indicators of sun exposure and HRT and CRC risk was not significant. These data, although exploratory, are consistent with evidence from the WHI suggesting a decrease in colorectal cancer risk may be associated with vitamin D exposure among postmenopausal women who are not taking HRT, but not among current HRT users.     

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 contraceptives and risk of breast cancer

A national population-based case-control study was conducted in New Zealand to assess the effects of hormonal contraception on breast-cancer risk. A total of 891 women aged 25 to 54 with a first diagnosis of breast cancer, and 1864 control subjects, randomly selected from the electoral rolls, were interviewed. The relative risk of breast cancer for women who had ever used oral contraceptives was 1.0 (95% confidence interval 0.82-1.3). There was no increase in risk with duration of use, even among women who had continued to use oral contraceptives for 14 or more years (relative risk = 1.1, 95% confidence interval 0.78-1.7). The risk of breast cancer was not increased by use of oral contraceptives for long periods before the first pregnancy or by starting use at a young age. Parity, age at menarche, family history of breast cancer, or history of benign breast disease did not modify the effect of oral contraceptives on breast-cancer risk. Relative risk estimates were slightly, although not significantly, increased during the first few years after starting oral contraception and in women under 35 years of age at diagnosis.     

Oral contraceptives, menopausal hormone therapy use and risk of B-cell non-Hodgkin lymphoma in the California Teachers Study

We examined oral contraceptive (OC) and menopausal hormonal therapy (MHT) use in relation to risk of B-cell non-Hodgkin lymphoma (NHL). Women under age 85 years participating in the California Teachers Study with no history of hematopoietic cancer were followed from 1995 through 2007. A total of 516 of 114,131 women eligible for OC use analysis and 402 of 54,758 postmenopausal women eligible for MHT use analysis developed B-cell NHL. Multivariable adjusted and age stratified Cox proportional hazards models were fit to estimate relative risks (RRs) and 95% confidence intervals (95% CI). Ever versus never OC use was marginally associated with lower B-cell NHL risk, particularly among women first using OCs before age 25 years (RR=0.72, 95% CI=0.51-0.99); yet, no duration-response effect was observed. No association was observed for ever versus never MHT use among postmenopausal women (RR=1.05, 95% CI=0.83-1.33) overall or by formulation (estrogen alone, ET, or estrogen plus progestin, EPT). Among women with no MHT use, having bilateral oophorectomy plus hysterectomy was associated with greater B-cell NHL risk than having natural menopause (RR=3.15, 95% CI=1.62-6.13). Bilateral oophorectomy plus hysterectomy was not associated with risk among women who used ET or EPT. These results indicate that exogenous hormone use does not strongly influence B-cell NHL risk.     

Body mass and endometrial cancer risk by hormone replacement therapy and cancer subtype.

Epidemiologic studies unequivocally show that greater body mass increases the risk of endometrial cancer, but whether risk varies by use of postmenopausal hormone therapy (HT), location of fat deposition, or cancer subtype is still unclear. We examined these associations among 33,436 postmenopausal women in the Cancer Prevention Study II Nutrition Cohort, who completed questionnaires on diet, lifestyle, and medical history at baseline in 1992. A total of 318 cases were eligible through June 2003. Cox-proportional hazards analyses were used to estimate multivariate-adjusted rate ratios (RR). As expected, adult body mass index (BMI) was a strong predictor of risk [RR, 4.70; 95% confidence interval (CI), 3.12-7.07 for BMI 35+ versus 22.5-25.0, P trend < 0.0001]. Use of estrogen plus progestin postmenopausal HT modified the association. Among never-users, risk was significantly linear across the entire range of BMI examined (RR, 0.51; 95% CI, 0.29-0.92 for <22.5 versus 22.5-25.0; RR, 4.41; 95% CI, 2.70-7.20 for > or =35 versus 22.5-25.0, P trend < 0.0001), but among ever estrogen plus progestin users, the association was not significant (P trend = 1.0; P interaction < 0.0001). We observed no difference in risk according to tendency for central versus peripheral fat deposition. Greater BMI (> or =30 versus <25.0) increased risk of both "type I" (classic estrogen pathway, RR, 4.22; 95% CI, 3.07-5.81) and "type II" (serous, clear cell, and all other high grade) cancers (RR, 2.87; 95% CI, 1.59-5.16). The increased risk of endometrial cancer across the range of BMI in women who never used postmenopausal HT stresses the need to prevent both overweight and obesity in women.     

Oral contraceptives and risk of familial breast cancer

The risk of breast cancer of oral contraceptive (OC) use in 1423 women from families with hereditary/familial breast cancer recruited through a cancer family clinic was analyzed in a matched case-control study. Ninety-eight women tested positive for a BRCA1 mutation. Hazard ratio for ever use of OCs adjusted for other risk factors was 0.90 (95% confidence interval (CI) 0.68-1.18) in the total data set and 2.00 (0.36-10.9) in BRCA1 mutation carriers. We did not find evidence for interaction between BRCA1 mutation status and OC use on breast cancer risk. Recent users had a statistically significant increase in risk with hazard ratios of 1.99, 2.05, and 1.69 for up to 5, 10, and 15 years since last OC use, while users with more than 15 years since last use had a reduction of risk to 0.69 compared to never users. We conclude that the effects of OC use on breast cancer risk in familial breast cancer may be similar to the effects in the general population. For BRCA1 mutation carriers, the point estimate is a doubling of risk, but CI is wide and no conclusion may be drawn from this study alone.     

Oral contraceptives, reproductive history and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition

Background:

Oral contraceptive use and reproductive factors may initiate long-term changes to the hormonal milieu and thereby, possibly influence colorectal cancer risk.

Methods:

We examined the association of hormonal and reproductive factors with risk of colorectal cancer among 337 802 women in the European Prospective Investigation into Cancer and Nutrition, of whom 1878 developed colorectal cancer.

Results:

After stratification for center and age, and adjustment for body mass index, smoking, diabetes mellitus, physical activity and alcohol consumption, ever use of oral contraceptives was marginally inversely associated with colorectal cancer risk (hazard ratio (HR), 0.92; 95% confidence interval (CI), 0.83–1.02), although this association was stronger among post-menopausal women (HR, 0.84; 95% CI: 0.74–0.95). Duration of oral contraceptive use and reproductive factors, including age at menarche, age at menopause, type of menopause, ever having an abortion, parity, age at first full-term pregnancy and breastfeeding, were not associated with colorectal cancer risk.

Conclusion:

Our findings provide limited support for a potential inverse association between oral contraceptives and colorectal cancer risk.     

Attributable causes of breast cancer and ovarian cancer in China: Reproductive factors, oral contraceptives and hormone replacement therapy

Objective:To provide an evidence-based,consistent assessment of the burden of breast cancer attributable to reproductive factors(RFs,including nulliparity,mean number of children,age at first birth and breastfeeding),use of oral contraceptives(OCs,restricted to the age group of 15-49 years),and hormone replacement therapy(HRT),as well as of the burden of ovarian cancer attributable to the mean number of children in China in 2005.Methods:We derived the prevalence of these risk factors and the relative risk of breast and ovarian cancer from national surveys or large-scale studies conducted in China.In the case of RFs,we compared the exposure distributions in 2001 and counterfactual exposure.Results:Exposure of RFs in 2001 was found to account for 6.74% of breast cancer,corresponding to 9,617 cases and 2,769 deaths,and for 2.78% of ovarian cancer(711 cases,294 deaths).The decrease in mean number of children alone was responsible for 1.47% of breast cancer and 2.78% of ovarian cancer.The prevalence of OC use was 1.74% and the population attributable fraction(PAF) of breast cancer was 0.71%,corresponding to 310 cases and 90 deaths.The PAF of breast cancer due to HRT was 0.31%,resulting in 297 cases and 85 deaths.Conclusion: RFs changes in China contributed to a sizable fraction of breast and ovarian cancer incidence and mortality, whereas HRT and OCs accounted for relatively low incidence of breast cancer in China.     

激素替代治疗与乳腺癌发病风险的关系

激素替代治疗（Hormone replacement therapy,HRT）可缓解妇女绝经后更年期症状,预防动脉硬化、心血管疾病和骨质疏松症,显著改善妇女绝经后的生活质量。乳腺是性激素的主要靶器官之一,内源性和外源性雌、孕激素均可对其产生影响,并可能在乳腺癌的发生发展过程中起到一定的作用。在普遍应用HRT的同时,HRT与乳腺癌的关系成为目前研究的热点。     

Oral contraceptives, reproductive factors and p53 gene expression in colorectal cancer

Protective effects of oral contraceptives and high parity on the development of colorectal cancer have been hypothesized. However, the epidemiological data are inconsistent. This inconsistency may be due in part to the biological heterogeneity of colorectal tumors. A recent investigation of hepatocellular carcinoma demonstrated an association between lack of p53 expression and oral contraceptive use. We investigated the relationship between oral contraceptive use and other reproductive factors with p53 over-expression in 64 post-menopausal women, 45-86 years of age, with non-familial colorectal adenocarcinoma. Fifty per cent (32/64) of colorectal tumors displayed nuclear over- expression of p53 protein. Women with a history of oral contraceptive use were significantly less likely to have p53 positive (+) tumors than women who never used oral contraceptives (P = 0.02). In contrast, tumors from women who had never been pregnant were more likely to be p53 + compared to tumors from parous women (P = 0.10). These data suggest that oral contraceptive use and pregnancy are associated with a p53 independent pathway in the development of colorectal cancer.