Cancer Epidemiology Biomarkers & Prevention最新文献

Background: Most relatives of women with ovarian cancer are unaware of their increased risk for cancer and their eligibility for genetic counseling. State cancer registries offer a platform to communicate about inherited risk to this population.

Methods: We conducted a two-arm randomized trial to test a theory-based communication intervention-Your Family Connects (YFC)-compared to the standard Georgia Cancer Registry (GCR) contact. A total of 1,938 eligible ovarian cancer survivors were randomly assigned to either the YFC arm (n = 969) or the Standard Care arm (n = 969). We assessed the number of ovarian cancer survivors and their close relatives who logged on to the study website by arm.

Results: Survivor reach was significantly higher in the Standard Care arm than YFC (20.8% vs. 15.2%, respectively; P < 0.001). However, reach to relatives was limited to listed relatives in the YFC arm (n = 20, 13.2%), with little participation from those in the Standard Care arm (n = 1, 0.4%). Pooling across arms, minority race, longer time since diagnosis, and older age were all significantly associated with a decreased likelihood that the survivor accessed the website.

Conclusions: The YFC intervention showed lower effectiveness for engaging survivors but was more effective than Standard Care in engaging at-risk relatives. Other factors (e.g., time since diagnosis) associated with lower reach must be considered in refining future outreach approaches.

Impact: Partnering with a state cancer registry to foster family communication about inherited cancer risk is feasible but the possibility for broad population reach warrants further testing.

Background: Cancers of ductal origin often express glycoprotein mucin 1 (MUC1), also known as CA15.3, with higher levels leading to poor prognosis. Conversely, anti-MUC1 antibodies develop in some patients, leading to better prognosis. We sought to identify epidemiologic factors associated with CA15.3 antigen or antibody levels.

Methods: Levels of CA15.3 antigen and anti-CA15.3 IgG antibodies were measured in archived sera from 2,302 mostly healthy women from the National Health and Nutritional Survey; and epidemiologic predictors of their levels were examined using multivariate and correlational analyses.

Results: Among racial groups, Black women had the highest levels of CA15.3 antigen and lowest levels of antibodies. Increasing body mass index and current smoking were associated with low anti-CA15.3 antibody levels. Low CA15.3 antigen levels were seen in oral contraceptive users and high levels in women who were pregnant or lactating at the time of blood collection, with the latter group also having high antibody levels. Past reproductive events associated with high antigen levels included the following: later age at menarche, having given birth, and history of endometriosis. Lower antigen levels were seen with increasing duration of OC use. Anti-CA15.3 antibody levels decreased with an increasing estimated number of ovulatory years.

Conclusions: Key determinants of CA.15.3 antigen or antibody levels include the following: race, body mass index, smoking, later menarche, childbirth, number of ovulatory cycles, and endometriosis.

Impact: This study supports the premise that known epidemiologic factors affecting risk for or survival after MUC1-expressing cancers may, at least partially, operate through their association with CA15.3 antigen or antibody levels.

Background: Pancreatic cancer is among the most fatal human cancers and the fourth leading cause of cancer death in the United States. Evidence suggests that chronic inflammation may play a role in pancreatic carcinogenesis and its inhibition through nonsteroidal anti-inflammatory drugs (NSAID) may reduce pancreatic cancer incidence.

Methods: We examined associations of total and individual NSAIDs with pancreatic cancer risk among postmenopausal women participating in the Women's Health Initiative observational study and clinical trial cohorts. Among 117,452 women, aged 55 to 79 years, 727 incident pancreatic cancer cases were reported over 18 years of follow-up. Cox regression was used to estimate hazard ratio (HR) and 95% confidence interval (CI) for associations between NSAIDs and pancreatic cancer risk.

Results: Relative to non-use, consistent use of any NSAID was inversely associated with pancreatic cancer risk (HR 0.71, 95% CI, 0.59-0.87), primarily driven by strong associations for aspirin use (HR 0.67, 95% CI, 0.52-0.86). Use of total or individual non-aspirin NSAIDs was not associated with pancreatic cancer. Upon stratified analysis, we observed stronger associations for NSAIDs among participants with prevalent diabetes (HR 0.28, 95% CI, 0.10-0.75) relative to those without (HR 0.75, 95% CI, 0.61-0.92; P-interaction = 0.03).

Conclusions: Additional large prospective studies with careful measurement of NSAID type, dose, and frequency are needed to further investigate the possibility of added benefit among individuals diagnosed with diabetes.

Impact: This study adds to existing evidence from prospective studies and clinical trials suggesting that use of aspirin may provide moderate benefit for pancreatic cancer prevention.

Overweight and obesity affect 71.2% of adults in the United States, with cancer survivors not far behind at 70.3%. Subgroups such as those diagnosed with acute lymphoblastic leukemia (ALL) face even greater challenges. The Exercise and Quality Diet after Leukemia (EQUAL) trial sought to address weight management issues among ALL survivors by implementing a remotely delivered weight loss intervention, leveraging the previously proven Practice-based Opportunities for Weight Reduction (POWER) program. Despite a strong foundation and design, the EQUAL trial yielded null results. Key differences in study populations and intervention contexts between the EQUAL and POWER trials, such as the lack of primary care physician involvement in EQUAL, contributed to these outcomes. EQUAL's failure to meet its accrual target and poor adherence among participants highlighted challenges in engaging this unique population. Contrary to EQUAL's conclusions, evidence from other studies supports the efficacy of remote interventions for weight loss among cancer survivors. The lack of qualitative assessment among ALL survivors and key integration to inform intervention adaptations undermined EQUAL's impact. However, EQUAL's impressive retention rate offers valuable insights. Lessons from EQUAL underscore the need for well-fitted, remotely delivered interventions and the importance of thoughtfully adapted and tailored approaches to specific survivor populations. See related article by Fiedmann et al., p. 1158.

Before implementing a biomarker in routine clinical care, it must demonstrate clinical utility by leading to clinical actions that positively affect patient-relevant outcomes. Randomly controlled early detection utility trials, especially those targeting mortality endpoint, are challenging due to their high costs and prolonged duration. Special design considerations are required to determine the clinical utility of early detection assays. This commentary reports on discussions among the National Cancer Institute's Early Detection Research Network investigators, outlining the recommended process for carrying out single-organ biomarker-driven clinical utility studies. We present the early detection utility studies in the context of phased biomarker development. We describe aspects of the studies related to the features of biomarker tests, the clinical context of endpoints, the performance criteria for later phase evaluation, and study size. We discuss novel adaptive design approaches for improving the efficiency and practicality of clinical utility trials. We recommend using multiple strategies, including adopting real-world evidence, emulated trials, and mathematical modeling to circumvent the challenges in conducting early detection utility trials.

Background: Estradiol and estrone are well-established risk factors for postmenopausal breast cancer (BC). Experimental evidence suggests that specific estrogen metabolites, produced via irreversible hydroxylation of estrone and estradiol at the 2- or 16-position may independently influence carcinogenesis.

Methods: We performed a nested case-control study of BC (328 BC cases; 639 controls) among postmenopausal women within the Nurses' Health Study (NHS)to examine the role of estrogens and estrogen metabolites (jointly referred to as EM). Plasma concentrations of each EM (unconjugated+conjugated forms) were measured by liquid chromatography-tandem mass spectrometry. Multivariable conditional logistic regression, adjusting for BC risk factors, estimated relative risks (RR) and 95% confidence intervals (CI) of BC across quintiles of individual EM, EM pathways, and pathway ratios. Associations by estrogen/progesterone receptor (ER/PR) status were analyzed by unconditional logistic regression.

Results: Estradiol and estrone were strongly associated with increased BC risk [estradiol: RRQ5v.Q1 (95% CI)=2.64 (1.64-4.26), estrone: 2.78 (1.74-4.45); both p-trends<0.001]. The 2-hydroxylation pathway was strongly associated with risk [RRQ5v.Q1=3.09 (1.81-5.27), p-trend<0.001], and remained so after adjusting for unconjugated estradiol [RRQ5v.Q1=2.23 (1.25-3.96), p-trend=0.01]. While the 16-hydroxylation pathway was modestly associated with risk [RRQ5v.Q1=1.62 (1.03-2.54), p-trend=0.01], the association was attenuated after unconjugated estradiol adjustment [RRQ5v.Q1=1.24 (0.77-1.99), p-trend=0.19]. Similar positive associations with the 2-pathway and 16-pathway were observed for ER+/PR+ and ER-/PR- tumors.

Conclusions: In this cohort of postmenopausal women, 2-hydroxylation of estrone and estradiol was associated with increased BC risk, independent of unconjugated estradiol.

Impact: These results highlight the need to revisit the role of estrogen metabolism in BC etiology and prevention.

Background: Various population-based studies have shown Hispanic/Latino ethnicity is a risk factor for worse survival in patients with gastric cancer linked to disparate access to care. We aimed to address whether Hispanic patients treated within safety-net hospital systems continue to experience this survival deficit compared to non-Hispanic patients.

Methods: We performed a retrospective cohort study comparing survival between Hispanic and non-Hispanic patients diagnosed with gastric adenocarcinoma between January 1, 2016 to December 31, 2020 within Los Angeles County's safety-net hospital system. Gastric cancer-specific survival was compared between the two cohorts using the Kaplan-Meier estimate and Cox proportional-hazards regression model.

Results: 448 patients who received care from five medical centers were included. 348 (77.7%) patients self-identified as Hispanic and 100 (22.3%) as non-Hispanic. Mean follow-up time was 2.0 years (median 0.91 years, IQR, 0.34-2.5 years). Hispanic patients were found to be diagnosed at a younger age (55.6 vs 60.7 years, p <0.01), demonstrate higher state area deprivation index (6.4 vs 5.0, p <0.01), and present with metastatic disease (59.8% vs 45%, p =0.04). After adjusting social and oncologic variables, Hispanic ethnicity remained an independent risk factor for worse survival (HR 1.56, [95% CI 1.06-2.28], p = 0.02).

Conclusions: Hispanic patients treated within a large, multi-center safety-net hospital system experience worse survival compared to non-Hispanic patients. This suggests ethnic disparities exist within safety-net hospital systems, independent of known clinicopathologic factors.

Impact: Improving outcomes for Hispanic patients with gastric cancer requires future efforts aimed at defining and addressing these unidentified barriers to care.

Background Monoclonal gammopathy of undetermined significance (MGUS) is the premalignant condition of multiple myeloma (MM). Given a lack of population-based screening for MGUS and its asymptomatic nature, the epidemiology of MGUS remains unknown. This study estimated age- and race/ethnicity-specific MGUS incidence and preclinical duration from MGUS to MM in the United States. Methods A previously published modeling approach was used to calculate national MGUS incidence using estimates of MGUS prevalence, MM incidence, MM-specific and all-cause mortality, and population age distribution from the National Health and Nutrition Examination Survey, 1999-2004, and Surveillance, Epidemiology, and End Results, 2000-2021. The estimated MGUS prevalence was divided by MGUS incidence to obtain preclinical duration of MM. Results MGUS incidence for non-Hispanic white (NHW) populations was 52, 86, 142, and 181 and for non-Hispanic black (NHB) population was 110, 212, 392, and 570 per 100,000 person-years at ages 50, 60, 70, and 80, respectively. The average preclinical duration was 20.5 (95% confidence interval, CI: 16.5, 26.1) years for the NHW population and 14.2 (95% CI: 11.5, 17.6) years for the NHB population. The cumulative risk of developing MGUS in age 50-85 was 2.8% (95% CI: 1.7%, 4.2%) for the NHW population and 6.1% (95% CI: 3.8%, 10.0%) for the NHB population. Conclusion NHB populations had a higher MGUS incidence rate at all ages and a shorter preclinical duration of MM compared to their NHW counterparts. Impact This study provides insights into the epidemiology of MGUS and enhances our understanding of the natural history of MM.

Background: High mammographic density is one of the strongest breast cancer risk factors; however, determinants of high mammographic density are understudied in Black women. We assessed growth and development factors across the lifecourse in relation to mammographic density.

Methods: Within the Black Women's Health Study (BWHS), we used Cumulus software to assess percent mammographic density from digital screening mammograms for 5,905 women ages 40-74. We fit linear regression models to quantify the association of lifecourse characteristics including birth weight, childhood somatotype, age at menarche, body mass index (BMI) at age 18, height, BMI at mammography, and adulthood waist-to-hip ratio with density overall and by age. We also performed a path analysis to assess the total and mediating effects of the growth and development factors on density.

Results: BMI at age 18, height, BMI at mammography, and waist-to-hip ratio were significantly and inversely associated with density. On path analysis, total effects of childhood somatotype (standardized  = -0.05, p <0.001), BMI at age 18 (standardized  = -0.13, p <0.001), BMI at mammography (standardized  = -0.22, p <0.001), and waist-to-hip ratio (standardized  = -0.04, p <0.001) were associated with density.

Conclusions: Several factors across the lifecourse - greater childhood somatotype, BMI at age 18, height, BMI at mammography, and waist-to-hip ratio - were associated with lower mammographic density in this cohort of Black women.

Impact: Body size closer to the time of mammography may be more meaningful in determining mammographic density, though early life adiposity also influences mammographic density.

Background: High-risk human papillomavirus (hrHPV)-based cervical cancer screening in the Netherlands led to a substantial increase in number of colposcopy referrals and low-grade lesions detected. Genotyping strategies may be employed to lower the screening-related burden.

Methods: We evaluated 14 triage strategies with genotyping (HPV16/18 or HPV16/18/31/33/45/52/58) for hrHPV-positive borderlineormilddyskaryosis (BMD)ornormal cytology,usingdata from a population-based hrHPV-based screening trial with 5-year interval (POBASCAM). We considered colposcopy referral at baseline, after 6-month repeat cytology and after 5-year hrHPV testing. Performance was evaluated by one-round positive and negative predictive value (PPVandNPV) for CIN3+ and by two-roundcolposcopy referral rate. To identify efficient strategies, they were ordered by the one-round colposcopy referral rate. Adjacent strategies were compared by the marginal PPV for detecting one additional CIN3+ (mPPV).

Results: The most conservative strategy (repeat cytology after BMD and HPV16/18/31/33/45/52/58-positive normal cytology, next round otherwise) yielded an mPPV of 28%, NPV of 98.2%, and two-round colposcopy referral rate of 47.2%. Adding direct referral after BMD or genotype-positive BMD yielded an mPPV ≤ 8.2%, NPV ≥ 98.5% and an increase in colposcopy referral rate of 1.9% to 6.5%. Adding direct referral after HPV16/18-positive normal cytology yielded an mPPV ≤ 3.5%, NPV ≥ 99.5% and an increase in colposcopy referral rate of 13.9%.

Conclusions: Direct colposcopy referral of women with BMD or normal cytology is unlikely to be efficient, but genotype-guided direct referral after BMD may be considered because the increase in colposcopies is limited.

Impact: hrHPV screening programs can become very efficient when immediate colposcopy referral is limited to women at highest CIN3+ risk. See related In the Spotlight, p. 979.