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.     

Hormone replacement therapy and breast cancer in former users of oral contraceptives--The Norwegian Women and Cancer study

Combined estrogen-progestin menopausal therapy (HRT) and combined estrogen-progestin contraceptives (OC) both increase breast cancer risk during current use and a few years after. We investigated risk of breast cancer in women who were users of HRT dependant on former history of OC use in a large, national population-based cohort study, the Norwegian Women and Cancer study (NOWAC). Exposure information was collected through postal questionnaires. Based on follow-up of 30,118 postmenopausal women by linkage to national registers of cancer, deaths, and emigration we revealed 540 incident breast cancer cases between 1996 and 2004. Compared to never users of either drugs current use of HRT gave a significant (p = 0.002) higher risk of breast cancer in former OC users, RR = 2.45 (95% CI 1.92-3.12), than among never users of OCs, RR = 1.67 (1.32-2.12). Relative risk of current use of HRT was similar for estrogen only and combinations with progestin added in ever users of OCs. The increased risk of breast cancer in current HRT users with a history of former OC use could have potential great impact on postmenopausal breast cancer risk as the proportion of postmenopausal women with former OC use will continue to increase.     

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.     

Oral contraceptive and IUD use and endometrial cancer: a population-based case-control study in Shanghai, China

Oral contraceptive (OC) and intrauterine device (IUD) use have been shown to be protective factors for endometrial cancer in several epidemiological studies; however, few studies have been conducted in Chinese populations. We evaluated the association between OC and IUD use and endometrial cancer risk in a population-based case-control study among Chinese women in Shanghai, China. The study included 1,204 newly diagnosed endometrial cancer cases and 1,212 age frequency-matched healthy controls. Logistic regression models were used to estimate adjusted odds ratios (OR) and their 95% confidence intervals (95% CI). In our study population, 18.5% cases and 24.9% controls reported having ever used OCs with an OR of 0.75 (95% CI, 0.60-0.93), after adjusting for known risk or protective factors for endometrial cancer. The risk of endometrial cancer decreased with long-term use of OCs with the OR for more than 72 months of use being 0.50 (95% CI, 0.30-0.85). The effect of OC use remained 25 or more years after cessation of use; the associated OR was 0.57 (95% CI = 0.42-0.78) as compared to nonusers. Similarly, fewer cases than controls had ever used IUD, with the multivariable adjusted OR being 0.53 (95% CI = 0.43-0.65). A reduction in risk was observed regardless the duration of use or age at first and last use. These results suggest that OC and IUD use may confer long-term protection against endometrial cancer.     

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.     

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.     

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.     

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 and risk of breast cancer in young women

Many studies have shown that oral contraceptive (OC) use increases a young woman's risk of breast cancer, although some studies suggest that the risk may be limited to recent use. The objective of this study was to determine what particular aspects of OC use could be important for breast cancer development at an early age in the cohort of women who had the opportunity to use OCs all of their reproductive life. The cases were first diagnosed with breast cancer at age 40 or younger between 1983 and 1988, and identified by the Los Angeles County Cancer Surveillance Program. Control subjects were individually matched to participating cases on birth date (within 36 months), race (white), parity (nulliparous versus parous), and neighborhood of residence. Detailed OC histories were obtained during in-person interviews with subjects. In general the risk estimates were small, and not statistically significant. Compared to no use, having used OCs for 12 years or more was associated with a modest non-significant elevated breast cancer risk with an odds ratio (OR) of 1.4 (95% confidence interval (CI)=0.8–2.4). Long-term (12 years or more) users of high-dose estrogen pills had a non-significant 60% higher breast cancer risk than never users (CI=0.9–3.2). Early use was associated with slightly higher ORs among young women (age 35), and among parous women. Recent use was associated with somewhat higher ORs among parous women and women above age 36. Analyses by stage, body weight, and family history yielded similar results. This study is consistent with a modest effect of early OC use on breast cancer risk in young women.     

Oral contraceptives and survival in breast cancer patients aged 20 to 54 years.

Recent oral contraceptive (OC) use is associated with modestly higher breast cancer incidence among younger women, but its impact on survival is unclear. This study examined the relationship between OC use before breast cancer diagnosis and survival. A population-based sample of 1,264 women aged 20 to 54 years with a first primary invasive breast cancer during 1990 to 1992 were followed up for 8 to 10 years. OC and covariate data were obtained by interviews conducted shortly after diagnosis and from medial records. All-cause mortality was ascertained through the National Death Index (n = 292 deaths). Age- and income-adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated by Cox regression methods. All-cause mortality was not associated with ever use of OCs or duration of use. Compared with nonusers, mortality estimates were elevated among women who were using OCs at diagnosis or stopped use in the previous year (HR, 1.57; 95% CI, 0.95-2.61). The HR for use of high-dose estrogen pills within 5 years before diagnosis was double that of nonusers (HR, 2.39; 95% CI, 1.29-4.41) or, if the most recent pill included the progestin levonorgestrel, compared with nonusers (HR, 2.01; 95% CI, 1.03-3.91). Because subgroup estimates were based on small numbers of OC users, these results should be cautiously interpreted. Overall, most aspects of OC use did not seem to influence survival, although there is limited evidence that OC use just before diagnosis, particularly use of some pill types, may negatively impact survival in breast cancer patients aged 20 to 54 years.     

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.     

High risk mammographic parenchymal patterns and diet: a case-control study

Mammographic parenchymal patterns are related to breast cancer risk and are also thought to be affected by diet. We designed a case-control study comprising 200 cases with high-risk (P2 and DY) mammographic parenchymal pattern and 200 controls with low-risk (N1 and P1) patterns in order to investigate the effect of food and nutrient intake on mammographic patterns. Mammograms were evaluated according to the Wolfe classification system. Dietary data were obtained from 7-day food diaries. Mean daily intake of nutrients was computed from standard UK food tables. The adjusted odds ratio (OR) of having a high-risk pattern in women in the highest tertile of total protein and carbohydrate intake was twice that of women in the lowest tertile (OR = 2.00; 95% confidence interval (CI) 1.06-3.77; P = 0.04 and OR = 1.93; 95% CI 1.03-3.59; P = 0.04 respectively). There was no excess risk for fat intake. In addition, there was no association between intake of vitamins and mammographic parenchymal patterns. Total meat intake was strongly and positively associated with high-risk patterns among post-menopausal women (OR = 2.50, 95% CI 1.09-5.69, P = 0.03). Our study suggests that certain macronutrients and foods such as protein, carbohydrate and meat intake influence the risk of breast cancer through their effects on breast tissue morphology, whereas fat and vitamins do not affect mammographic density. It seems that parenchymal pattern acts as an informative biomarker of the effect of some macronutrient and foodstuffs intake on breast cancer risk.     

Early oral contraceptive use and breast cancer among premenopausal women: final report from a study in southern Sweden

In southern Sweden during the 1960s, women began to use oral contraceptives (OCs) extensively at a young age. This case-control study investigates the relationship between the use of OCs and breast cancer development in women in southern Sweden diagnosed in the early 1980s. The risk for breast cancer after OC use among premenopausal women was modeled, after adjustment was made for age, age at menarche, and age at first full-term pregnancy or parity. Both the duration of OC use before 25 years of age and commencement of OC use at a young age were associated with a significant increase in the risk of breast cancer as well as a significant trend. The duration of OC use before the first full-term pregnancy was associated with an increased risk of breast cancer, but it did not show a significant trend. The total duration of OC use was weakly, but not significantly, associated with breast cancer development. The odds ratio for women starting OC use before 20 years of age was 5.8 [95% confidence interval (CI), 2.6-12.8]; for women using OCs for greater than 5 years before age 25, it was 5.3 (95% CI, 2.1-13.2); and for women using OCs for greater than or equal to 8 years before first full-term pregnancy, it was 2.0 (95% CI, 0.8-4.7). In multivariate analyses including the different measurements of OC use, only starting age of OC use was significantly associated with breast cancer. The exposure-response relationship between duration of OC use and risk of breast cancer depended on the age at first use of OCs. Given a fixed duration of OC use, the risk increased with younger starting age of OC use. The findings point to the importance of the early reproductive years as risk determinants for breast cancer after OC use.     

Use of oral contraceptives and breast cancer risk: The Norwegian-Swedish Women's Lifestyle and Health Cohort Study.

Current use of oral contraceptives (OCs) has been reported to increase breast cancer risk slightly. In 1991/1992, a prospective cohort study specifically designed to examine the role of hormonal contraceptives in relation to breast cancer was conducted in Norway and Sweden. This study was entitled Women's Lifestyle and Health. Of 196,000 invited women aged 30-49 years, 106,844 women answered a 4-page questionnaire. Altogether, 103,027 women providing information on contraceptive use were included in the analysis presented here, and 1,008 primary invasive breast cancers were diagnosed throughout 1999 (end of follow-up). Proportional hazard regression was used to calculate relative risks (RRs) with adjustment for age and other possible confounders. An increased breast cancer risk was observed among women who were current/recent users of OCs of any type at the start of follow-up [RR, 1.6; 96% confidence interval (CI), 1.2-2.1]. Current/recent use (i.e., use in the year preceding cohort enrolment) of combined OCs (RR, 1.5; 95% CI, 1.0-2.0) and progestin-only pills (RR, 1.6; 95% CI, 1.0-2.4) entailed similar levels of increased risk. An increased risk of borderline significance was found among short-term (i.e., less than 13 months) users before age 20 years (RR, 1.3; 95% CI, 1.0-1.7) and before first full-term pregnancy (RR, 1.4; 95% CI, 1.0-1.8). Long-term users of OCs were at a higher risk of breast cancer than never users (test for trend, P = 0.005). Current/recent use of OCs is associated with an increased breast cancer risk. Use of combined OCs and progestin-only pills seem to increase the risk at the same level.     

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.     

Risk factors for adrenal cancer: An exploratory study

Adrenal cancer is a heterogeneous group of neoplasms with unknown etiology. In search of risk factors, we conducted a case-control study based on data from the 1986 National Mortality Followback Survey, which included a questionnaire sent to the next of kin of almost 20,000 deceased adults (age ≥ 25 years) in the United States. Information was obtained on a large number of items, including use of cigarettes, alcohol, oral contraceptives (OCs), height and weight and food consumption patterns. A total of 176 subjects who died of adrenal cancer (88 men and 88 women) and 352 controls (176 men and 176 women) who died of causes unrelated to smoking, drinking or OCs (for female controls) were included in the study. Although information on histologic type was not available, most cases were estimated from incidence surveys to be adrenocortical carcinoma, with a small percentage being malignant pheochromocytoma or neuroblastoma. An increased risk was associated with heavy smoking (≥25 cigarettes/day) among men (odds ratio [OR] = 2.0, 95% confidence interval [CI] 1.0–4.4) but not women. No clear association was seen for alcohol use, height and weight or food consumption patterns in either sex. Among women, increased risks were found for ever users of OCs (OR = 1.8, 95% CI 1.0–3.2) and especially those who used them before age 25 (OR = 2.5, 95% CI 1.2–5.5). When the analysis was restricted to subjects with spousal respondents, more pronounced risks were seen for ever users of OCs and for those who used OCs before age 25. Our findings suggest that cigarette smoking and use of OCs may increase the risk of adrenal cancer, but additional studies are needed with more detailed information on risk factors and histologic type of adrenal cancer. © 1996 Wiley-Liss, Inc.     

Oral contraceptive use, reproductive factors, and colorectal cancer risk: findings from Wisconsin.

We investigated the association of oral contraceptive (OC) use and reproductive factors with colorectal cancer risk in a large population-based case-control study. Cases were women ages 20 to 74 years, living in Wisconsin, with a new diagnosis of colon (n = 1,122) or rectal (n = 366) cancer. Control participants were randomly selected from population lists of similarly aged female Wisconsin residents (n = 4,297). Risk factor information was collected through structured telephone interviews. Compared with never users, OC users had an odds ratio (OR) of 0.89 [95% confidence interval (95% CI), 0.75-1.06] for colorectal cancer. OC use associations did not differ significantly between colon and rectal cancer sites; however, when compared with never users, recent OC users (<14 years) seemed at reduced risk of rectal cancer (OR, 0.53; 95% CI, 0.28-1.00). Women with age at first birth older than the median (23 years) had 0.83 times the risk of colon cancer compared with women with age at first birth below the median (95% CI, 0.70-0.98). We observed an inverse trend between increasing parity and rectal cancer risk (P = 0.05). Compared with nulliparous women, women with five or more births had 0.66 times the risk of rectal cancer (95% CI, 0.43-1.02). Compared with postmenopausal women, premenopausal women were at reduced risk (OR, 0.67; 95% CI, 0.47-0.97) of colorectal cancer. No significant associations were observed between colorectal cancer risk and age at menarche or age at menopause. These findings suggest differential roles of reproductive factors in colon and rectal cancer etiology.     

High-risk mammographic parenchymal patterns and anthropometric measures: a case-control study

Mammographic parenchymal patterns are related to breast cancer risk and are also affected by anthropometric measure. We carried out a case-control study comprising 200 cases with high-risk (P2 and DY) mammographic parenchymal pattern and 200 controls with low-risk (N1 and P1) patterns in order to investigate the effect of body size and shape and breast size on mammographic patterns. Women in the highest quartile of body mass index (BMI) distribution were significantly less likely to have a high-risk pattern (odds ratio (OR) = 0.21, 95% confidence interval (CI) 0.08-0.52, P-value for trend = 0.001) compared to those in the lowest quartile. Relative to women with a waist to hip ratio (WHR) of less than 0.75, the OR of having a high-risk pattern in women with a WHR greater than 0.80 was 0.30 (95% CI 0.14-0.63). Breast size as measured by cup size was significantly and negatively related to high-risk pattern. Our study indicates that both BMI and WHR are negatively associated with high-risk patterns. However, both phenomena are associated with increased risk of breast cancer in postmenopausal women. This negative confounding of two positive risk factors means that the effect of parenchymal patterns on risk will tend to be underestimated when not adjusted for BMI and WHR and vice versa. Thus we may have underestimated the importance of BMI and mammographic parenchymal patterns in the past. Further studies are needed to determine a measure of parenchymal density that is independent of anthropometric measures and breast size.     

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).     

Combined effect of oral contraceptive use and hormone replacement therapy on breast cancer risk in postmenopausal women

OBJECTIVE: We examined breast cancer risk related to lifetime exposure to oral contraceptives (OCs) and hormone replacement therapy (HRT) in postmenopausal women. METHODS: The Women's Contraceptive and Reproductive Experiences (CARE) Study was a population-based case-control study that included 1847 postmenopausal women with incident invasive breast cancer, and 1932 control subjects, identified using random digit dialing. RESULTS: 45% of cases and 49% of controls used both OCs and HRT. OC users were not at increased risk regardless of subsequent HRT exposure. HRT users who had used OCs previously did not have a higher risk of breast cancer than women with no exposure to OCs. We observed a negative interaction (p-value: 0.032) of combined hormone replacement therapy (CHRT) and past OC use. The increase in risk with CHRT was stronger in women who had never used OCs in the past (odds ratio: 1.05; 95% confidence interval: 1.01-1.10 per year of exclusive CHRT use) than in women who had used OCs (odds ratio: 1.00; 95% confidence interval: 0.97-1.03). CONCLUSIONS: We found no indication that adverse effects of exposure to OCs or HRT appeared only in the presence of the other hormone or were exacerbated by exposure to the other hormone.