Cancer Epidemiology Biomarkers & Prevention最新文献

Background: Localized prostate tumors show significant spatial heterogeneity, with regions of high-grade disease adjacent to lower grade disease. Consequently, prostate cancer biopsies are prone to sampling bias, potentially leading to underestimation of tumor grade. To study the clinical, epidemiologic, and molecular hallmarks of this phenomenon, we conducted a prospective study of grade upgrading: differences in detected prostate cancer grade between biopsy and surgery.

Methods: We established a prospective, multi-institutional cohort of men with grade group 1 (GG1) prostate cancer on biopsy who underwent radical prostatectomy. Upgrading was defined as detection of GG2+ in the resected tumor. Germline DNA from 192 subjects was subjected to whole-genome sequencing to quantify ancestry, pathogenic variants in DNA damage response genes, and polygenic risk.

Results: Of 285 men, 67% upgraded at surgery. PSA density and percent of cancer in pre-prostatectomy positive biopsy cores were significantly associated with upgrading. No assessed genetic risk factor was predictive of upgrading, including polygenic risk scores for prostate cancer diagnosis.

Conclusions: In a cohort of patients with low-grade prostate cancer, a majority upgraded at radical prostatectomy. PSA density and percent of cancer in pre-prostatectomy positive biopsy cores portended the presence of higher-grade disease, while germline genetics was not informative in this setting. Patients with low-risk prostate cancer, but elevated PSA density or percent cancer in positive biopsy cores, may benefit from repeat biopsy, additional imaging or other approaches to complement active surveillance.

Impact: Further risk stratification of patients with low-risk prostate cancer may provide useful context for active surveillance decision-making.

Background: Risk factors including smoking, alcohol intake, physical activity (PA), and sleep patterns have been associated with cancer risk. Clonal hematopoiesis (CH), including mosaic chromosomal alterations and clonal hematopoiesis of indeterminate potential, is linked to increased hematopoietic cancer risk and could be used as common preclinical intermediates for the better understanding of associations of risk factors with rare hematologic malignancies.

Methods: We analyzed cross-sectional data from 478,513 UK Biobank participants without hematologic malignancies using multivariable-adjusted analyses to assess the associations between lifestyle factors and CH types.

Results: Smoking was reinforced as a potent modifiable risk factor for multiple CH types, with dose-dependent relationships persisting after cessation. Males in socially deprived areas of England had a lower risk of mosaic loss of chromosome Y (mLOY), females with moderate/high alcohol consumption (2-3 drinks/day) had increased mosaic loss of the X chromosome risk [OR = 1.17; 95% confidence interval (CI), 1.09-1.25; P = 8.31 × 10-6] compared with light drinkers, active males (moderate-high PA) had elevated risks of mLOY (PA category 3: OR = 1.06; 95% CI, 1.03-1.08; P = 7.57 × 10-6), and men with high body mass index (≥40) had reduced risk of mLOY (OR = 0.57; 95% CI, 0.51-0.65; P = 3.30 × 10-20). Sensitivity analyses with body mass index adjustment attenuated the effect in the mLOY-PA associations (IPAQ2: OR = 1.03; 95% CI, 1.00-1.06; P = 2.13 × 10-2 and IPAQ3: OR = 1.03; 95% CI, 1.01-1.06; P = 7.77 × 10-3).

Conclusions: Our study reveals associations between social deprivation, smoking, and alcohol consumption and CH risk, suggesting that these exposures could contribute to common types of CH and potentially rare hematologic cancers.

Impact: This study underscores the impact of lifestyle factors on CH frequency, emphasizing social, behavioral, and clinical influences and the importance of sociobehavioral contexts when investigating CH risk factors.

Background: Benzene exposure has been associated with increased risk of leukemia and other cancers; however, epidemiologic evidence is inconsistent for the latter, and confounding from smoking and alcohol was rarely adjusted.

Methods: We investigated associations between occupational benzene exposure and risk of leukemia, lymphoma, myeloma, and lung, stomach, liver, and kidney cancers in a population-based cohort of 61,377 men, ages 40 to 74 years. A job-exposure matrix, constructed by industrial hygienists specifically for the study population, was used to derive cumulative benzene exposure from all jobs held. Cox regressions were performed to estimate adjusted HRs (aHR) and 95% confidence intervals (CI) for benzene-cancer risk associations with adjustment for potential confounders.

Results: Over 15 years of follow-up, 1,145 lung cancer, 656 stomach cancer, 445 liver cancer, 243 kidney cancer, 100 leukemia, 124 lymphoma, and 46 myeloma cases were identified. Benzene exposure >550 mg/m3 was associated with an increased risk of leukemia (aHR = 2.3; 95% CI, 1.1-4.5), lung cancer (aHR = 1.2; 95% CI, 1.0-1.6), and stomach cancer (aHR = 1.4; 95% CI, 1.0-1.9); benzene exposure was associated with early cancer diagnosis age. The benzene-leukemia and benzene-stomach cancer associations followed a linear dose-response pattern (Plinear = 0.016 and 0.023), whereas the benzene-lung cancer association was evident at higher exposure levels (Pnonlinear = 0.027). Alcohol consumption modified the benzene-leukemia association (aHR = 3.0; 95% CI, 1.1-8.3 for drinkers and aHR = 0.9; 95% CI, 0.4-2.0 for nondrinkers, Pinteraction = 0.047).

Conclusions: Benzene exposure was associated with an increased risk of leukemia, stomach cancer, and lung cancer. Alcohol consumption may modify the benzene-leukemia association, although estimates are imprecise.

Impact: Our study provides additional evidence that benzene exposure increases cancer risk beyond leukemia, information important for policymakers to develop programs to mitigate cancer risk among benzene-exposed workers.

Lesbian, gay, bisexual, transgender, and queer (LGBTQ+) cancer survivors disproportionately experience physical and mental health comorbidities compared with their heterosexual and cisgender counterparts. A recent study by Waters and colleagues evaluates associations between LGBTQ+ identity and physical and mental health comorbidities and activity limitations using Behavioral Risk Factor Surveillance System data. Consistent with previous work, their findings suggest that LGBTQ+ survivors have higher odds of several chronic conditions, including asthma, depressive disorders, heart attacks, kidney disease, stroke, and diabetes, as well as reporting disabilities related to vision and cognition and difficulty with activities of daily living, including walking, dressing, and running errands. Waters and colleagues expand on previous work by providing estimates separately for sexual orientation and gender identity. Their results for lesbian, gay, and bisexual survivors were similar to those for LGBTQ+ survivors overall. In novel findings, they report much stronger associations between identifying as transgender or gender nonconforming and nearly all comorbidities compared with cisgender survivors, including those who identify as lesbian, gay, or bisexual. This commentary advocates for the importance of future work considering the drivers of disparities in cancer outcomes based on sexual orientation and gender identity. See related article by Waters et al., p. 1405.

Background: We investigated clinical characteristics and prostate cancer survival patterns among Latino patients considering nativity compared with non-Latino Black (NLB) and non-Latino White (NLW) patients.

Methods: We used data from the California Cancer Registry (1995-2021), which included 347,540 NLW, 50,032 NLB, and 75,238 Latino patients with prostate cancer. Frequencies of sociodemographic and clinical variables were assessed using χ2 tests. Multivariable regression models were fitted to evaluate determinants of treatment reception, Gleason upgrade, and survival differences. Exploratory analyses were conducted grouping Latino cases into US born and non-US born by country of origin.

Results: Compared with NLW, NLB cases had the greatest proportion of younger patients, whereas non-US-born Latino patients had the greatest proportion of low socioeconomic status and uninsured patients. Non-US-born Latinos showed a greater proportion of diagnoses completed with <6 core biopsies, Gleason >8, stage IV tumors, and metastasis. Multivariable analyses showed that compared with NLW, Latino patients were as likely to receive treatment, whereas NLB cases were less likely (OR = 0.81; 95% confidence interval, 0.67-0.98; P = 0.029). Compared with NLW, non-US-born Latino cases were less likely to die of prostate cancer (HR = 0.78; 95% confidence interval, 0.64-0.94; P = 0.011), with no difference reported for NLB cases.

Conclusions: Considering sociodemographic and clinical characteristics, non-US-born Latino patients with prostate cancer had better survival than NLW. This highlights the need to identify key determinants of these survival differences and the importance of sociodemographic and clinical determinants in survival disparities.

Impact: Our study emphasizes the importance of considering nativity among Latino patients to understand prostate cancer disparities and outcomes in this population.

Background: We evaluated the association between metabolic syndrome (obesity plus two metabolic risk factors) and breast cancer outcomes according to molecular subtype.

Methods: This population-based prospective cohort consisted of 3,267 women aged 20-69 diagnosed with a first primary invasive breast cancer from 2004-2015 in the Seattle-Puget Sound region. Breast cancer was categorized into three subtypes based on estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression: luminal (ER+), triple-negative (ER-/PR-/HER2-), and HER2-overexpressing (H2E) (ER-/HER2+). We used time-varying Cox models to assess the association between prevalent and incident metabolic syndrome and risks of recurrence, breast cancer-specific mortality, and all-cause mortality.

Results: Metabolic syndrome was associated with a greater risk of recurrence (HR:3.24; 95% CI:1.13-9.33) and breast cancer-specific mortality (HR:5.34; 95% CI:2.32-12.31) only for the H2E subtype, and greater risks of all-cause mortality for luminal (HR:1.92; 95% CI:1.37-2.68), H2E (HR:5.09; 95% CI:2.51-10.32), and all cases combined (HR:1.90; 95% CI:1.42,2.53). We also observed heterogeneity in recurrence and mortality outcomes across specific components of metabolic syndrome and molecular subtypes.

Conclusions: Metabolic syndrome is associated with all-cause mortality among women with breast cancer and with breast cancer-specific mortality among women with the H2E subtype.

Impact: These results highlight the importance of managing comorbidities to decrease the risk for adverse outcomes among breast cancer survivors.

Background: Modifying dietary behaviors into healthier habits may attenuate the risk of colorectal cancer (CRC) risk. This study aimed to investigate the association between dietary changes and the risk of CRC.

Methods: Following dietary recommendations for red and processed meat, fruit and vegetables, and alcohol consumption, we classified 50,640 participants into poor and good adherence groups in the UK Biobank. Changes in dietary habits were defined as stable poor, poor to good, good to poor, and stable to good adherence. A Cox proportional hazard model was used to examine the association between dietary changes and CRC risk.

Results: Women were more likely to follow dietary recommendations than men. After a median of 3.3 years from the latest follow-up, 8,328 (16.4%) participants followed an improved dietary habit and 5,808 (11.5%) participants had a worsened diet. Compared to men who stably consumed fruit and vegetables <5 servings/day, those who increased their consumption to ≥5 servings/day were related to CRC risk reduction (hazard ratio: 0.24, [0.09-0.63]). However, the beneficial associations of increased fruit and vegetable consumption were not statistically significant in women (hazard ratio: 0.41, [0.11-1.56]).

Conclusions: Our findings support the evidence that increasing fruit and vegetable intake could serve as a beneficial strategy to mitigate CRC risk in men.

Impact: Participants from the UK Biobank significantly changes their adherence to dietary recommendations during the follow-up. Increasing fruit and vegetable consumption was inversely associated with CRC risk among men.

Background: The COVID-19 pandemic and associated shutdowns disrupted healthcare access and resulted in decreased cancer screenings. Cancer diagnosis delays have concerning downstream effects on late-stage cancer, especially for marginalized populations.

Methods: The study population included 349,458 adults in the California Cancer Registry diagnosed with cancer between January 2019-December 2021, during which California experienced two stay-at-home orders. We examined the percentage of late-stage (III-IV) cancer diagnoses across five periods: Pre-Pandemic (January 2019-February 2020), Shutdown #1 (March-June 2020), Post-Shutdown #1 (July-November 2020), Post-Shutdown #2 (December 2020-March 2021), and Post-Vaccine Rollout (April-December 2021). To examine the association between time-period and late-stage diagnoses, we conducted a multivariable log binomial regression model adjusted for sociodemographic and neighborhood factors.

Results: The percentage of late-stage cancer diagnoses increased during Shutdown #1 (+5.2%) and returned to baseline Post-Vaccine Rollout. Groups with notably higher increases in the percentage of late-stage cancer (vs. overall population) during Shutdown #1 include: Pacific Islander (+13.7%), Thai (+11.2%), Chinese (+8.1%), Native Hawaiian (+7.4%), Filipino (+6.6%), and uninsured (+7.4%). Uninsured (vs. private insurance) (PR: 1.41), low neighborhood SES (nSES) (vs. high) (PR: 1.19), and racial and ethnic minoritized groups (vs. NH White) (PR's: 1.04-1.19) had higher likelihood for late-stage cancer diagnosis.

Conclusions: The pandemic exacerbated late-stage cancer disparities for racial and ethnic minoritized groups, underinsured, and low nSES communities in California (2020-2021).

Impact: Interventions to improve cancer screening must be focused on racial and ethnic minoritized, underinsured, and low nSES communities, as they are likely to be more vulnerable to healthcare disruptions like the pandemic.

Background: Despite the promise of mail-based human papillomavirus (HPV) self-collection programs for increasing cervical cancer screening, few have been evaluated in the United States. We report the results of a mail-based HPV self-collection program for underscreened women living in Appalachia.

Methods: We conducted a group randomized trial during 2021-2022 in the Appalachian regions of Kentucky, Ohio, Virginia, and West Virgnia. Participants were women ages 30-64 who were underscreened for cervical cancer and from a participating health system. Participants in the intervention group (n=464) were mailed an HPV self-collection kit followed by telephone-based patient navigation (if needed), and participants in the usual care group (n=338) were mailed a reminder letter to get a clinic-based cervical cancer screening test. Generalized linear mixed models compared cervical cancer screening between study groups.

Results: Overall, 14.9% of participants in the intervention group and 5.0% of participants in the usual care group were screened for cervical cancer. The mail-based HPV self-collection intervention increased cervical cancer screening compared to the usual care group (OR=3.30, 95% CI: 1.90-5.72, p=0.005). One or more high-risk HPV types were detected in 10.5% of the returned HPV self-collection kits. Among participants in the intervention group who patient navigators attempted to contact, 44.2% were successfully reached.

Conclusions: HPV self-collection increased cervical cancer screening, and future efforts are needed to determine how to optimize such programs, including the delivery of patient navigation services.

Impact: Mail-based HPV self-collection programs are a viable strategy for increasing cervical cancer screening among underscreened women living in Appalachia.

Background: Ferritin, an iron storage protein and acute phase reactant, has been implicated in various aspects of human health and disease, including cancer. Previous studies have identified elevated serum ferritin (SF) levels in several cancer types, but a comprehensive examination across different malignancies remains lacking. This study aims to fill this gap by utilizing anonymized data from Maccabi Health Services (MHS), one of Israel's largest health organizations, to explore the association between elevated SF levels and the diagnosis of different malignancies.

Methods: An extensive dataset from MHS, comprising 2.7 million members, including 1.3 million individuals who underwent SF level testing, was analyzed. Odds Ratios (OR) and 95% confidence intervals (CI) were calculated to assess the association between high SF levels and cancer diagnosis. Subgroup analysis was conducted to investigate variations across different malignancies.

Results: The analysis revealed a significant association between elevated SF levels and cancer diagnosis among MHS members, with an OR of 1.9 (95% CI 1.71-2.15). Sub- group analysis unveiled differences in the association across malignancy types, with hematological, hepatobiliary and respiratory malignancies more strongly associated with high SF levels.

Conclusions: This study provides further support for the link between elevated SF levels and malignancy, leveraging a vast dataset from MHS, underscoring potential utilities of elevated SF levels as a potential indicator for cancer with a variable role among different malignancy types.

Impact: The identification of elevated SF levels as a potential indicator for underlying malignancy for seemingly-healthy individuals.