European trends in cervical cancer mortality in relation to national screening programs, 1985–2014

BackgroundCervical cancer is the fourth leading oncological cause of death in women. Variable trends in cervical cancer mortality have been observed across Europe, despite the widespread adoption of screening programs. This variability has previously been attributed to heterogeneity in the quality of screening programs.MethodsAge-standardized cervical cancer death rates for European countries between 1985 and 2014 were analyzed using Joinpoint regression. Countries were dichotomized based on year of implementation and population invitational coverage of national population-based cervical cancer screening programs. National cervical cancer mortality trends during the study period were compared based on this classification.ResultsDecreasing trends in mortality were observed in all European countries with the specific exceptions of Bulgaria, Greece and Latvia. The highest rates of cervical cancer mortality throughout the study period were in Romania (16.0-14.9/100,000) and the lowest rates in Italy (1.4-1.2/100,000). The greatest percentage decline in mortality was observed in the United Kingdom and the greatest absolute reduction in mortality was seen in Hungary. European countries which implemented a national population-based cervical cancer screening program prior to 2009 demonstrated greater improvements in cervical cancer mortality outcomes compared to those that did not (p = 0.016).ConclusionCervical cancer mortality is improving in most European countries; however, substantial variation remains. Trends in mortality were associated with the time of implementation of national population-based cervical screening programs.     

Trends in socioeconomic inequalities in cervical,breast, and colorectal cancer screening participation among women in Japan, 2010–2019

BackgroundIt is known that socioeconomic status (SES) influences the outcome of cancer treatment and this could partly be explained by decreased use of cancer screening services by people of lower SES. Many studies have indicated that low SES, including low educational attainment or unstable employment, was related to nonparticipation in cancer screening. However, studies investigating trends in SES inequalities within cancer screening participation are limited. Our objective was to examine trends in SES inequalities in cervical, breast, and colorectal cancer screening participation among women in Japan between 2010 and 2019.MethodsWe analyzed 189,442, 168,571, 163,341, and 150,828 women in 2010, 2013, 2016, and 2019 respectively, using nationally representative cross-sectional surveys. The main outcome variables are participation in each cancer screening. We used educational attainment and employment status as measures for SES. Multivariable logistic regression analysis, adjusted for age, marital status, educational attainment, and employment status was performed to evaluate the associations between SES and nonparticipation in each cancer screening.ResultsOverall participation rates in each cancer screening increased between 2010 and 2019. Low educational attainment and non-permanent employment status were related to nonparticipation in each cancer screening and inequality according to employment status increased within each screening participation during the study period. For example, dispatched workers were more likely to not participate in cervical cancer screening than permanent workers: in 2010, [aOR 1.11 95 %CI: 1.01 –1.21], and in 2019, [aOR 1.46 95 %CI: 1.34–1.60]. The inequality was greatest in colorectal cancer screening nonparticipation, followed by breast and cervical screening.ConclusionsAlthough the participation rates in each cancer screening have increased, inequality in participation in terms of employment status widened among women in Japan between 2010 and 2019. Reducing inequalities in cancer screening participation is essential for cancer screening intervention policies.     

Inverse Sampling in Case Control Studies Involving a Rare Exposure

In case-control studies where the outcome is not uncommon but the exposure is rare, inverse sampling may be used to reduce the total number of subjects required to find a fixed number of exposed cases and controls. The sampling distribution is negative binomial rather than binomial. Logistic regression for adjustment of covariates may be implemented on the computer program GLIM by the appropriate use of macros. An example is given.     

Proteomic analysis of estrogen response of premalignant human breast cells using a 2-D liquid separation/mass mapping technique

A 2-D liquid-phase separation method based on chromatofocusing and nonporous silica RP-HPLC followed by ESI-TOF-MS was used to analyze proteins in whole cell lysates from estrogen-treated and untreated premalignant, estrogen-responsive cell line MCF10AT1 cells. 2-D mass maps in the pH range 4.6-6.0 were generated with good correlation to theoretical M(r) values for intact proteins. Proteins were identified based on intact M(r), pI and PMF, or MS/MS sequencing. About 300 unique proteins were identified and 120 proteins in mass range 5-75 kDa were quantified upon treatment of estrogen. Around 40 proteins were found to be more highly expressed (>four-fold) and 17 were down-regulated (>four-fold) in treated cells. In our study, we found that many altered proteins have characteristics consistent with the development of a malignant phenotype. Some of them have a role in the ras pathway or play an important role in signal pathways. These changed proteins might be essential in the estrogen regulation mechanism. Our study highlights the use of the MCF10AT1 cell line to examine estrogen-induced changes in premalignant breast cells and the ability of the 2-D mass mapping technique to quantitatively study protein expression changes on a proteomic scale.     

Evaluating the use of friend or family controls in epidemiologic case-control studies

BackgroundTraditional methodologies for identifying and recruiting controls in epidemiologic case-control studies, such as random digit dialing or neighborhood walk, suffer from declining response rates. Here, we revisit the feasibility and comparability of using alternative sources of controls, specifically friend and family controls.MethodsWe recruited from a recently completed case-control study of non-Hodgkin lymphoma (NHL) among women in Los Angeles County where controls from the parent study were ascertained by neighborhood walk. We calculated participation rates and compared questionnaire responses between the friend/family controls and the original matched controls from the parent study.ResultsOf the 182 NHL case patients contacted, 111 (61%) agreed to participate in our feasibility study. 70 (63%) provided contact information for potential friend and/or family member controls. We were able to successfully contact and recruit a friend/family member for 92% of the case patients. This represented 46 friend controls and 54 family controls. Family controls significantly differed from original matched controls by sex and household income. Other characteristics were similar between friend controls and the original study’s neighborhood controls.ConclusionThe apparent comparability of neighborhood controls to friend and family controls among respondents in this study suggests that these alternative methods of control identification can serve as a complementary source of eligible controls in epidemiologic case-control studies.     

Clinical and radiological features of breast tumors according to history of false-positive results in mammography screening

BackgroundWomen with a false-positive result after a screening mammogram have an increased risk of cancer detection in subsequent participations, especially after assessments involving cytology or biopsy. We aimed to compare women's personal characteristics, tumoral features and the radiological appearance of cancers with and without a previous false-positive result generated by additional imaging or invasive procedures.MethodsFrom 1996 to 2007, 111,098 women aged 45–69 years participated in four population-based breast cancer screening programs in Spain, and 1281 cancers were detected. We included all cancers detected in subsequent screenings (n = 703) and explored the occurrence of previous false-positive results. We identified false-positives requiring additional imaging or invasive procedures. Differences on tumoral features (invasiveness, tumor size, and lymph node status) and radiological appearance were assessed by Chi-square test, and agreement between the location of cancer and prior suspicious by Cohen's kappa coefficient. A multivariate analysis was preformed to evaluate the effect of previous screening results and age on the odds of presenting an in situ carcinoma.ResultsAmong the 703 cancers detected in subsequent screenings, 148 women (21.1%) had a previous false-positive result. Of these, 105 were by additional imaging and 43 by invasive procedures. Women with prior false-positive result requiring invasive assessment, compared to women with negative tests, and women with prior false-positive requiring additional imaging, had a higher proportion of in situ carcinomas (31.7%, 15.3%, 12.9%, respectively; p = 0.014) and microcalcifications (37.2%, 20.2%, 9.5%, respectively; p = 0.003). The proportion of in situ carcinomas was even higher in women over 60 years (39.2%, 12.5%, 13.0%, respectively; p = 0.001). Ipsilateral cancer was observed in 65.7% of cases with prior cytology or biopsy (k = 0.479; 95%CI: 0.330–0.794).ConclusionA large number of in situ malignancies and calcification patterns were found among women with prior false-positive result in mammography screening requiring cytology or biopsies, suggesting progression from a previously benign lesion.     

Identification of breast cancer metastasis-associated proteins in an isogenic tumor metastasis model using two-dimensional gel electrophoresis and liquid chromatography-ion trap-mass spectrometry

To better understand the molecular mechanisms underlying breast cancer metastasis and search for potential markers for metastatic progression, we have developed a highly metastatic variant of human MDA-MB-435 breast cancer cell line through in vivo stepwise selection of pulmonary metastatic cells caused by parental MDA-MB-435 cells in the athymic mice. Comparative proteomic analysis using 2-DE and LC-IT-MS revealed that 102 protein spots were reproducibly altered more than three-fold between the selected variant and its parental counterpart. Eleven differentially expressed protein spots were identified with high confidence using SEQUEST with uninterpreted tandem mass raw data. Cathepsin D precursor, peroxiredoxin 6 (PDX6), heat shock protein 27 (HSP27), HSP60, tropomyosin 1 (TPM1), TPM2, TPM3, TPM4, 14-3-3 protein epsilon, and tumor protein D54 were up-regulated in the highly metastatic variant, whereas alpha B-crystalline (CRAB) was only detected in its parental counterpart. Differential expression was confirmed for four proteins including PDX6, CRAB, TPM4, and HSP60 by real-time quantitative PCR and Western blotting analysis in our model. Immunohistochemical analysis in 80 breast cancer donors demonstrated a significant association of TPM4 (p = 0.002), HSP60 (p = 0.001), PDX6 (p = 0.002) but not CRAB (p = 0.113) staining with the presence of lymph node metastasis. In addition, TPM4 staining was also associated with clinical stage (p = 0.000), but no significant association was found between TPM4, PDX6, CRAB, and HSP60 expression and tumor size, hormone receptor, and HER-2 status (p > 0.05). The functional implication of these identified proteins was also discussed. These proteomic data are valuable and informative for understanding breast cancer metastasis and searching for potential markers for metastatic progression.