Relative and Attributable Risk for Cervical Cancer: A Comparative Study in the United States and Italy

Parazzini F {Istituto di Ricerche Farmacologiche ‘Mario Negri' via Eritrea 62,20157 Milan, Italy), Hildesheim A, Ferraroni M, La Vecchia C and Brinton LA. Relative and attributable risk for cervical cancer: A comparative study in Italy and the United States. International Journal of Epidemiology 1990, 19: 539-545. The attributable risk for invasive cervical cancer in the US and Italian populations has been estimated in relation to main ‘aetiological' factors (number of sexual partners, age at first intercourse, parity, oral contraceptive use and smoking) and history of Pap smear using data from two case-control studies conducted in the US (466 cases and 788 controls) and Italy (528 cases and 456 controls). The risk of cervical cancer increased in both studies with multiple sexual partners, decreasing age at first intercourse, higher parity, oral contraceptive use and smoking. Levels of exposure to various risk factors were markedly different in the two countries (ie number of sexual partners, frequency of oral contraceptive use and smoking were greater in the US). Multiple Pap smears and a short interval since last Pap smear strongly reduced risk of cervical cancer in both populations, although screening was much more widespread in the US study population, with only 9% of controls reporting no previous smear versus 38% of the Italian control series. The combined population attributable risk for the five ‘aetiological' risk factors was slightly greater in the US study (76%) than in the Italian one (69%), chiefly because of a higher prevalence of exposure to sexual factors in US study women. A substantially larger proportion of Italian cases were due in part to deficiency in screening (46% in US and 84% in Italy). Thus, further inclusion of the effect of screening programmes (number of Pap smears and time since last Pap) led to an overall proportion of cases attributable to the examined risk factors of 87% in the US and 95% in Ital

Risk Factors for Triple-Negative Breast Cancer in Women Under Age 45

Little is known about the etiologic profile of triple-negative breast cancer (negative for estrogen receptor/progesterone receptor/human epidermal growth factor), a breast cancer subtype associated with high mortality and inadequate therapeutic options. We undertook this study to assess the risk for triple-negative breast cancer among women 45 years of age and younger in relation to demographic/lifestyle factors, reproductive history, and oral contraceptive use. Study participants were ascertained in two previous population-based, case-control studies. Eligible cases included all primary invasive breast cancers among women ages 20 to 45 years in the Seattle-Puget Sound area, diagnosed between January 1983 and December 1992, for whom complete data was obtained for estrogen receptor, progesterone receptor, and human epidermal growth factor status (n = 897; including n = 187 triple-negative breast cancer cases). Controls were age matched and ascertained via random digit dialing. Oral contraceptive use >/=1 year was associated with a 2.5-fold increased risk for triple-negative breast cancer (95% confidence interval, 1.4-4.3) and no significantly increased risk for non-triple-negative breast cancer (Pheterogeneity = 0.008). Furthermore, the risk among oral contraceptive users conferred by longer oral contraceptive duration and by more recent use was significantly greater for triple-negative breast cancer than non-triple-negative breast cancer (Pheterogeneity = 0.02 and 0.01, respectively). Among women /=1 year was 4.2 (95% confidence interval, 1.9-9.3), whereas there was no significantly increased risk with oral contraceptive use for non-triple-negative breast cancer among women </=40 years, nor for triple-negative breast cancer or non-triple-negative breast cancer among women 41 to 45 years of age. In conclusion, significant heterogeneity exists for the association of oral contraceptive use and breast cancer risk between triple-negative breast cancer and non-triple-negative breast cancer among young women, lending support to a distinct etiology

Dissemination and Sustainability of a Hospital-Wide Hand Hygiene Program Emphasizing Positive Reinforcement

Objective. To increase and sustain hospital-wide compliance with hand hygiene through a long-term ongoing multidimensional improvement program emphasizing behavioral factors. Design. Quasi-experimental short study (August 2000-November 2001) and descriptive time series (April 2003-December 2006). Setting. A 450-bed teaching tertiary-care hospital. Interventions. An initial intervention bundle was introduced in pilot locations that addressed cognitive behavioral factors, which included access to alcohol sanitizer, education, and ongoing audit and feedback. The bundle was subsequently disseminated hospital-wide, along with a novel approach focused on behavior modification through positive reinforcement and annually changing incentives. Results. A total of 36,123 hand hygiene opportunities involving all categories of healthcare workers from 12 inpatient units were observed from October 2000 to October 2006. The rate of compliance with hand hygiene significantly improved after the intervention in 2 cohorts over the first year (from 40% to 64% of opportunities and from 34% to 49% of opportunities; P< .001, compared with the control group). Mean compliance rates ranged from 19% to 41% of 4174 opportunities (at baseline), increased to the highest levels of 73%-84% of 6,420 opportunities 2 years after hospital-wide dissemination, and remained improved at 59%-81% of 4,990 opportunities during year 6 of the program. Conclusion. This interventional cohort study used a behavioral change approach and is one of the earliest and largest institution-wide programs promoting alcohol sanitizer from the United States that has shown significant and sustained improvements in hand hygiene compliance. This creative campaign used ongoing frequent audit and feedback with novel use of immediate positive reinforcement at an acceptable cost to the institutio

Epidemiologic Risk Factors for In Situ and Invasive Breast Cancers Among Postmenopausal Women in the National Institutes of Health-AARP Diet and Health Study

Comparing risk factor associations between invasive breast cancers and possible precursors may further our understanding of factors related to initiation versus progression. Accordingly, among 190,325 postmenopausal participants in the National Institutes of Health-AARP Diet and Health Study (1995-2011), we compared the association between risk factors and incident ductal carcinoma in situ (DCIS; n = 1,453) with that of risk factors and invasive ductal carcinomas (n = 7,525); in addition, we compared the association between risk factors and lobular carcinoma in situ (LCIS; n = 186) with that of risk factors and invasive lobular carcinomas (n = 1,191). Hazard ratios and 95% confidence intervals were estimated from multivariable Cox proportional hazards regression models. We used case-only multivariable logistic regression to test for heterogeneity in associations. Younger age at menopause was associated with a higher risk of DCIS but lower risks of LCIS and invasive ductal carcinomas (P for heterogeneity < 0.01). Prior breast biopsy was more strongly associated with the risk of LCIS than the risk of DCIS (P for heterogeneity = 0.04). Increased risks associated with use of menopausal hormone therapy were stronger for LCIS than DCIS (P for heterogeneity = 0.03) and invasive lobular carcinomas (P for heterogeneity < 0.01). Associations were similar for race, age at menarche, age at first birth, family history, alcohol consumption, and smoking status, which suggests that most risk factor associations are similar for in situ and invasive cancers and may influence early stages of tumorigenesis. The differential associations observed for various factors may provide important clues for understanding the etiology of certain breast cancers

Do breast implants after a mastectomy affect subsequent prognosis and survival?

In a large study, published in this issue of Breast Cancer Research, Le and colleagues report that women receiving implants after mastectomies for early-stage breast cancer experience lower breast cancer mortality than women not receiving implants. Assessment of survival patterns among women receiving reconstructive implants is complex given unique patient characteristics, disease attributes, and treatment patterns. The interpretation of reduced mortality from breast cancer must be assessed in light of significantly reduced risks of death from most other causes. In contrast, patients receiving post-mastectomy implants had elevated rates of suicide, consistent with findings among women with cosmetic implants. Additional well-designed investigations are needed to clarify survival patterns among women receiving reconstructive implants

Cell-Cycle Protein Expression in a Population-Based Study of Ovarian and Endometrial Cancers

Aberrant expression of cyclin-dependent kinase (CDK) inhibitors is implicated in the carcinogenesis of many cancers, including ovarian and endometrial cancers. We examined associations between CDK inhibitor expression, cancer risk factors, tumor characteristics, and survival outcomes among ovarian and endometrial cancer patients enrolled in a population-based case control study. Expression (negative vs. positive) of three CDK inhibitors (p16, p21, p27) and ki67 was examined with immunohistochemical staining of tissue microarrays. Logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for associations between biomarkers, risk factors, and tumor characteristics. Survival outcomes were available for ovarian cancer patients and examined using Kaplan-Meier plots and Cox proportional hazards regression. Among ovarian cancer patients (n=175), positive p21 expression was associated with endometrioid tumors (OR=12.22, 95% CI=1.45-102.78) and higher overall survival (log-rank p=0.002). In Cox models adjusted for stage, grade, and histology, the association between p21 expression and overall survival was borderline significant (hazard ratio=0.65, 95% CI=0.42-1.05). Among endometrial cancer patients (n=289), positive p21 expression was inversely associated with age (OR ≥ 65 years of age=0.25, 95% CI=0.07-0.84) and current smoking status (OR: 0.33, 95% CI 0.15, 0.72) compared to negative expression. Our study showed heterogeneity in expression of cell-cycle proteins associated with risk factors and tumor characteristics of gynecologic cancers. Future studies to assess these markers of etiological classification and behavior may be warranted

Post-diagnosis body mass index and mortality among women diagnosed with endometrial cancer: Results from the Women\u27s Health Initiative.

Higher body mass index (BMI) measured before endometrial cancer diagnosis has been associated with greater risk of developing endometrial cancer and higher mortality, but the association between BMI measured after diagnosis and mortality risk is unclear. We identified 467 women (91 deaths) in the Women\u27s Health Initiative (WHI) with information on BMI measured after diagnosis and used Cox proportional hazards regression to generate hazard ratios (HR) and 95% confidence intervals (CI) for all-cause mortality. Comparing BMI 35+ with/m2, we observed no association with all-cause mortality (HR = 1.02, 95% CI 0.55-1.91). Our study does not support the hypothesis that higher BMI after endometrial cancer diagnosis is associated with poorer survival

Ovarian cancer risk and common variation in the sex hormone-binding globulin gene: a population-based case-control study

BACKGROUND: The sex hormone-binding globulin (SHBG) is a carrier protein that modulates the bio-availability of serum sex steroid hormones, which may be involved in ovarian cancer. We evaluated whether common genetic variation in SHBG and its 3' neighbor ATP1B2, in linkage disequilibrium, is associated with the risk of epithelial ovarian cancer. METHODS: The study population included 264 women with ovarian carcinoma and 625 controls participating in a population-based case-control study in Poland. Five common single nucleotide polymorphisms (SNPs) in SHGB and five in ATP1B2 were selected to capture most common variation in this region. RESULTS: None of the SNPs evaluated was significantly associated with ovarian cancer risk, including the putative functional SNPs SHBG D356N (rs6259) and -67G>A 5'UTR (rs1799941). However, our data were consistent with a decreased ovarian cancer risk associated with the variant alleles for these two SNPs, which have been previously associated with increased circulating levels of SHBG. CONCLUSION: These data do not support a substantial association between common genetic variation in SHBG and ovarian cancer risk