Giske Ursin

Reproductive factors and breast cancer risk according to joint estrogen and progesterone receptor status: a meta-analysis of epidemiological studies

IntroductionAlthough reproductive factors have been known for decades to be associated with breast cancer risk, it is unclear to what extent these associations differ by estrogen and progesterone receptor (ER/PR) status. This report presents the first meta-analysis of results from epidemiological studies that have investigated parity, age at first birth, breastfeeding, and age at menarche in relation to ER+PR+ and ER-PR- cancer risk.Materials and methodsWe calculated summary relative risks (RRs) and corresponding 95% confidence intervals (CIs) using a fixed effects model.ResultsEach birth reduced the risk of ER+PR+ cancer by 11% (RR per birth = 0.89, 95% CI = 0.84–0.94), and women who were in the highest age at first birth category had, on average, 27% higher risk of ER+PR+ cancer compared with women who were in the youngest age at first birth category (RR = 1.27, 95% CI = 1.07–1.50). Neither parity nor age at first birth was associated with the risk of ER-PR- cancer (RR per birth = 0.99, 95% CI = 0.94–1.05; RR of oldest versus youngest age at first birth category = 1.01, 95% CI = 0.85–1.20). Breastfeeding and late age at menarche decreased the risk of both receptor subtypes of breast cancer. The protective effect of late age at menarche was statistically significantly greater for ER+PR+ than ER-PR- cancer (RR = 0.72 for ER+PR+ cancer; RR = 0.84 for ER-PR- cancer, p for homogeneity = 0.006).ConclusionOur findings suggest that breastfeeding (and age at menarche) may act through different hormonal mechanisms than do parity and age at first birth.

Influence of individual and combined health behaviors on total and cause-specific mortality in men and women: The United Kingdom Health and Lifestyle Survey

BACKGROUND Physical activity, diet, smoking, and alcohol consumption have been shown to be related to mortality. We examined prospectively the individual and combined influence of these risk factors on total and cause-specific mortality. METHODS The prospective cohort study included 4886 individuals at least 18 years old from a United Kingdom-wide population in 1984 to 1985. A health behavior score was calculated, allocating 1 point for each poor behavior: smoking; fruits and vegetables consumed less than 3 times daily; less than 2 hours physical activity per week; and weekly consumption of more than 14 units of alcohol (in women) and more than 21 units (in men) (range of points, 0-4). We examined the relationship between health behaviors and mortality using Cox models and compared it with the mortality risk associated with aging. RESULTS During a mean follow-up period of 20 years, 1080 participants died, 431 from cardiovascular diseases, 318 from cancer, and 331 from other causes. Adjusted hazard ratios and 95% confidence intervals (CIs) for total mortality associated with 1, 2, 3, and 4 poor health behaviors compared with those with none were 1.85 (95% CI, 1.28-2.68), 2.23 (95% CI, 1.55-3.20), 2.76 (95% CI, 1.91-3.99), and 3.49 (95% CI, 2.31-5.26), respectively (P value for trend, <.001). The effect of combined health behaviors was strongest for other deaths and weakest for cancer mortality. Those with 4 compared with those with no poor health behaviors had an all-cause mortality risk equivalent to being 12 years older. CONCLUSION The combined effect of poor health behaviors on mortality was substantial, indicating that modest, but sustained, improvements to diet and lifestyle could have significant public health benefits.

A meta-analysis of body mass index and risk of premenopausal breast cancer.

Increased body mass index (BMI) has been found to be associated with elevated risk of postmenopausal breast cancer. Whether BMI is related to premenopausal breast cancer has not yet been established. We performed a meta-analyses of data from 23 studies that provided information on BMI and incidence of premenopausal breast cancer. Overall, the data support a modest inverse association. For a BMI difference of 8 kg per m2, that is, the difference between a thin person and someone who is morbidly obese, the random effects estimate of the rate ratio from the four cohort studies was 0.70 [95% confidence interval (CI) = 0.54–0.91], and the random effects estimate of the odds ratio from the 19 case-control studies was 0.88 (95% CI = 0.76–1.02). Because of substantial heterogeneity among the study-specific estimates, however, we also examined the influence of certain aspects of study design. Case-control studies with community controls had a more inverse association, whereas case-control studies that interviewed cases shortly after diagnosis applied the same exclusion criteria to cases and controls, or with confounder adjustment beyond age had a more positive association between BMI and breast cancer. Possible reasons for the discrepancies among the case-control studies are discussed.

Meat consumption and the risk of type 2 diabetes: a systematic review and meta-analysis of cohort studies

Aims/hypothesisDiet is thought to play an important role in the aetiology of type 2 diabetes. Previous studies have found positive associations between meat consumption and the risk of type 2 diabetes, but the results have been inconsistent. We conducted a systematic review and meta-analysis of cohort studies of meat consumption and type 2 diabetes risk.MethodsWe searched several databases for cohort studies on meat consumption and type 2 diabetes risk, up to December 2008. Summary relative risks were estimated by use of a random-effects model.ResultsWe identified 12 cohort studies. The estimated summary RR and 95% confidence interval of type 2 diabetes comparing high vs low intake was 1.17 (95% CI 0.92–1.48) for total meat, 1.21 (95% CI 1.07–1.38) for red meat and 1.41 (95% CI 1.25–1.60) for processed meat. There was heterogeneity amongst the studies of total, red and processed meat which, to some degree, was explained by the study characteristics.Conclusions/interpretationThese results suggest that meat consumption increases the risk of type 2 diabetes. However, the possibility that residual confounding could explain this association cannot be excluded.

Prevalence and Predictors of BRCA1 and BRCA2 Mutations in a Population-Based Study of Breast Cancer in White and Black American Women Ages 35 to 64 Years

Although well studied in families at high-risk, the roles of mutations in the BRCA1 and BRCA2 genes are poorly understood in breast cancers in the general population, particularly in Black women and in age groups outside of the very young. We examined the prevalence and predictors of BRCA1 and BRCA2 mutations in 1,628 women with breast cancer and 674 women without breast cancer who participated in a multicenter population-based case-control study of Black and White women, 35 to 64 years of age. Among cases, 2.4% and 2.3% carried deleterious mutations in BRCA1 and BRCA2, respectively. BRCA1 mutations were significantly more common in White (2.9%) versus Black (1.4%) cases and in Jewish (10.2%) versus non-Jewish (2.0%) cases; BRCA2 mutations were slightly more frequent in Black (2.6%) versus White (2.1%) cases. Numerous familial and demographic factors were significantly associated with BRCA1 and, to a lesser extent, BRCA2 carrier status, when examined individually. In models considering all predictors together, early onset ages in cases and in relatives, family history of ovarian cancer, and Jewish ancestry remained strongly and significantly predictive of BRCA1 carrier status, whereas BRCA2 predictors were fewer and more modest in magnitude. Both the combinations of predictors and effect sizes varied across racial/ethnic and age groups. These results provide first-time prevalence estimates for BRCA1/BRCA2 in breast cancer cases among understudied racial and age groups and show key predictors of mutation carrier status for both White and Black women and women of a wide age spectrum with breast cancer in the general population.

Hormone replacement therapy regimens and breast cancer risk

OBJECTIVE Hormone replacement therapy (HRT) has increased in the United States over the past 2 decades in response to reports of long‐term health benefits. A relationship between HRT and breast cancer risk has been observed in a number of epidemiological studies. In 2002, the Womens Health Initiative Randomized Controlled Trial reported an association between continuous combined HRT and breast cancer risk. The objective of this study was to examine the association between breast cancer risk and HRT according to regimen and duration and recency of use. METHODS A multicenter, population‐based, case‐control study was conducted in five United States metropolitan areas from 1994 to 1998. Analyzed were data from 3823 postmenopausal white and black women (1870 cases and 1953 controls) aged 35–64 years. Odds ratios (ORs) were calculated as estimates of breast cancer risk using standard, unconditional, multivariable logistic regression analysis. Potential confounders were included in the final model if they altered ORs by 10% or more. Two‐sided P values for trend were computed from the likelihood ratio statistic. RESULTS Continuous combined HRT was associated with increased breast cancer risk among current users of 5 or more years (1.54; 95% confidence interval 1.10, 2.17). Additionally, a statistically significant trend indicating increasing breast cancer risk with longer duration of continuous combined HRT was observed among current users (P = .01). There were no positive associations between breast cancer risk and other HRT regimens. CONCLUSION Our data suggest a positive association between continuous combined HRT and breast cancer risk among current, longer term users. Progestin administered in an uninterrupted regimen may be a contributing factor. Risk dissipates once use is discontinued.

Relation of regimens of combined hormone replacement therapy to lobular, ductal, and other histologic types of breast carcinoma†

The incidence of invasive lobular carcinoma has been increasing among postmenopausal women in some parts of the United States. Part of this may be due to changes in classification over time. However, the use of combined (estrogen and progestin) hormone replacement therapy (CHRT) also has increased during the last decade and may account in part for the increase in invasive lobular breast carcinoma.

The NICHD Women's Contraceptive and Reproductive Experiences Study: Methods and Operational Results

PURPOSE This paper presents methods and operational results of a population-based case-control study examining the effects of oral contraceptive use on breast cancer risk among white and black women aged 35-64 years in five U.S. locations. METHODS Cases were women newly diagnosed with breast cancer during July 1994 through April 1998. Controls were identified through random digit dialing (RDD) using unclustered sampling with automated elimination of nonworking numbers. Sampling was density-based, with oversampling of black women. In-person interviews were conducted from August 1994 through December 1998. Blood samples were obtained from subsets of cases and controls, and tissue samples were obtained from subsets of cases. A computerized system tracked subjects through study activities. Special attention was devoted to minimizing exposure misclassification, because any exposure-disease associations were expected to be small. RESULTS An estimated 82% of households were screened successfully through RDD. Interviews were completed for 4575 cases (2953 whites; 1622 blacks) and 4682 controls (3021 whites; 1661 blacks). Interview response rates for cases and controls were 76.5% and 78.6%, respectively, with lower rates for black women and older women. CONCLUSIONS The methodologic details of this large collaboration may assist researchers conducting similar investigations.

Cervical carcinoma and reproductive factors: Collaborative reanalysis of individual data on 16,563 women with cervical carcinoma and 33,542 women without cervical carcinoma from 25 epidemiological studies.

The International Collaboration of Epidemiological Studies of Cervical Cancer has combined individual data on 11,161 women with invasive carcinoma, 5,402 women with cervical intraepithelial neoplasia (CIN)3/carcinoma in situ and 33,542 women without cervical carcinoma from 25 epidemiological studies. Relative risks (RRs) and 95% confidence intervals (CIs) of cervical carcinoma in relation to number of full‐term pregnancies, and age at first full‐term pregnancy, were calculated conditioning by study, age, lifetime number of sexual partners and age at first sexual intercourse. Number of full‐term pregnancies was associated with a risk of invasive cervical carcinoma. After controlling for age at first full‐term pregnancy, the RR for invasive cervical carcinoma among parous women was 1.76 (95% CI: 1.53–2.02) for ≥≥7 full‐term pregnancies compared with 1–2. For CIN3/carcinoma in situ, no significant trend was found with increasing number of births after controlling for age at first full‐term pregnancy among parous women. Early age at first full‐term pregnancy was also associated with risk of both invasive cervical carcinoma and CIN3/carcinoma in situ. After controlling for number of full‐term pregnancies, the RR for first full‐term pregnancy at age <17 years compared with ≥≥25 years was 1.77 (95% CI: 1.42–2.23) for invasive cervical carcinoma, and 1.78 (95% CI: 1.26–2.51) for CIN3/carcinoma in situ. Results were similar in analyses restricted to high‐risk human papilloma virus (HPV)‐positive cases and controls. No relationship was found between cervical HPV positivity and number of full‐term pregnancies, or age at first full‐term pregnancy among controls. Differences in reproductive habits may have contributed to differences in cervical cancer incidence between developed and developing countries.

Diet and premenopausal bilateral breast cancer: A case-control study

We investigated associations between diet and premenopausal bilateral breast cancer in a familial matched case-control study. We studied 140 cases from population-based registries in Los Angeles County (California) and Connecticut, and from the major hospitals in the southern parts of the Province of Quebec. Unaffected sisters of the cases served as matched controls (222 total). Dietary intake were assessed with a food frequency questionnaire. Total fat, monounsaturated fat, polyunsaturated fat, oleic acid, and linoleic acid intake was inversely associated with premenopausal bilateral breast cancer risk. Consumption of carbohydrates (and sweetened beverages) was associated with an increased risk. We observed no associations for dietary fiber, antioxidants, or major food groupings, but we did observe inverse associations for intake of low fat dairy products and tofu. These findings suggest that monounsaturated and polyunsaturated fats, as well as soy foods, might reduce the risk of premenopausal bilateral breast cancer.