Cancer Epidemiology Biomarkers & Prevention最新文献

Background: Cancer survivors are at increased risk for cardiometabolic comorbidities following cancer treatment which may be further exacerbated by cannabis and alcohol use. We aimed to examine the direct relationships of cannabis, alcohol, and the co-use of both substances with cardiometabolic risk factors and to explore disparities by race/ethnicity and sex.

Methods: Cross-sectional data were extracted from adult cancer survivors in the "All of Us" from 2018-2022. Cannabis use was defined as occasional or frequent/regular cannabis use (vs never) in the past three months and hazardous alcohol intake (AUDIT-C >3 for females, AUDIT-C >4 for males) vs non-hazardous in the past year, respectively. Co-use was defined as participants who engaged in regular cannabis and hazardous alcohol intake. We identified binary cardiovascular, immune, and metabolic systems biomarkers, with high values defined by clinically established cutoffs or >75th percentile. We used multivariable logistic regression adjusting for socio-demographic and clinical factors.

Results: In our sample (N=7,054), 7.6% were Hispanic, 6.2% were Black, and 86.2% were White cancer survivors. Less than 5% of Hispanic and White survivors reported substance co-use compared to 7% of Black survivors. Compared to never users, co-users were 1.58(95% CI=1.14-2.19) more likely to have high blood pressure. No significant associations were found between co-use and immune biomarkers or sex differences.

Conclusion: Co-use of cannabis and hazardous alcohol may worsen high blood pressure in survivors, who are at higher risk for cardiometabolic comorbidities.

Impact: The study investigates substance use and cardiometabolic biomarkers, urging more research on their effects on cancer survivors.

Background: Identification of groups at a high-risk of gastric cancer (GC) could facilitate targeted screening in countries with a low GC incidence. Our aim was to identify such high-risk groups, based on individual-level population data on migration history and socioeconomic status (SES) in the Netherlands.

Methods: In this retrospective cohort study, patient data from the Netherlands cancer registry were linked to demographic data of Statistics Netherlands in the period 2010-2022. GC incidence rates in the 14 largest immigrant populations were compared to those born in the Netherlands. Odds ratios (ORs) were computed per birthplace and controlled for age, sex and SES. Additionally, we investigated GC risk among second-generation immigrants and by SES.

Results: Immigrant populations at a significantly higher GC risk compared to the general population were identified. Specifically, foreign-born first-generation immigrants from Bosnia-Herzegovina (OR: 2.42), Turkey (OR: 2.22) and China (OR: 1.92) showed elevated risk. While low SES increased the odds of developing GC, first-generation immigrants remained at higher risk even after controlling for SES. Second-generation immigrants did not have a significantly higher risk of developing GC.

Conclusions: Certain first-generation immigrants remain at an elevated risk for GC despite migration to a low-risk region. Identification of these high-risk groups should be used to facilitate targeted GC prevention.

Impact: Potential benefits of targeted Helicobacter pylori test-and-treat policy in immigrant populations should be explored in clinical and modelling studies. Primary care physicians should be cognizant of high-risk groups, facilitating the early-detection of cancer within these populations.

Background: In 2012, the U.S. Preventive Services Task Force (USPSTF) recommended against prostate cancer screening using the prostate-specific antigen (PSA) test for all age groups. In 2018 the USPSTF's recommendation shifted from a "D" (not recommended) to a "C" (selectively offering PSA-based screening based on professional judgment and patient preferences) in men ages 55-69. Limited reliable county-level prostate cancer screening data is available for cancer surveillance purposes.

Methods: Utilizing data from the National Health Interview Survey (NHIS) and Behavioral Risk Factor Surveillance System (BRFSS) collected in 2012-2019, state- and county-level small area models were developed for estimating PSA testing. Model diagnosis, internal validation, and external validation examining associations of PSA testing and prostate cancer incidence were conducted.

Results: Model-based estimates of PSA testing rate were produced for all U.S. states and 3,142 counties for two data periods: 2012-2016 and 2018-2019. Geographic variations across counties were demonstrated through maps. Moderate positive correlations between PSA-based screening and prostate cancer incidence were observed, for example, the state-level weighted Pearson's correlation coefficients were 0.5025 (p-value=0.0002) and 0.3691 (p-value=0.0077) for 2012-2016 and 2018-2019, respectively.

Conclusions: These modeled estimates showed improved precision and adjusted for the differences between BRFSS and NHIS. The approach of combining NHIS and BRFSS utilized strengths of the larger sample size of BRFSS and generally higher response rates and better household coverage from the NHIS.

Impact: The resulting small area estimates offer a valuable resource for the cancer surveillance community, aiding in targeted interventions, decision-making, and further research endeavors.

Background: Acute lymphoblastic leukemia (ALL) is the most common type of cancer among children. Tobacco exposure during gestation has been investigated as a potential risk factor, but its role remains undefined. Given tobacco's toxicological profile as a DNA damaging agent, we examined the impact of DNA repair gene variability as a source of vulnerability to tobacco exposure risk for ALL.

Methods: Leveraging demographic and genotype data from two large California-based ALL epidemiology studies, we used logistic regression, MinimumP (MinP) statistical method and permutation tests to examine interactions between DNA repair genes and prenatal tobacco exposure.

Results: We found statistically significant interactions between prenatal tobacco exposure and DNA repair genes RECQL (minP= 1.00x 10-4, FDR-P value = 1.86x 10-2) and TDG (minP= 1.00x 10-4, FDR-P value = 1.86 x 10-2) regarding childhood ALL risk. Notable interactions in the homologous recombination pathway were observed among Latino children, while non-Latino White children displayed significant interactions in the base excision repair and nucleotide excision repair pathways.

Conclusions: Our study highlights the significance of DNA repair genes and pathways when evaluating environmental exposure to tobacco smoke, suggesting that genetic variability within these pathways could impact vulnerability in the development of childhood ALL.

Impact: This study highlights the significant impact of genetic variation interacting with prenatal tobacco exposure on ALL risk. Further research is needed to understand these interactions and their implications for ALL etiology. Expanding studies to other gene-environment interactions will aid in developing targeted prevention, diagnosis, and treatment strategies for pediatric oncology.

Poverty is a carcinogen and a leading cause of cancer disparities and overall mortality in the United States. Poverty is often viewed as an individual failure for "being poor," but in fact, poverty is structurally driven, intergenerational, and place-based that socially deprives and denies human potential. Disparities in timely cancer prevention, diagnosis, treatment, survivorship, and survival disproportionally impact people living in poverty and especially in persistent poverty areas, an extreme form of place-based poverty that affects communities over multiple generations. There has been some progress made to address place-based conditions that exacerbate poverty, such as the NCI's initiative on persistent poverty. However, gross inequality and cancer disparities continue to exist and persist. The time is now to accelerate the development of research-informed strategies and solutions with communities along with multisectoral collaborations with education, housing, occupation/workforce, foster care, criminal justice, transportation, and data collection systems. This commentary discusses the structural, place-based, and generational context of poverty, illustrates how entrenched inequities shape poor cancer outcomes, and describes opportunities for future research.

Background: Cancer rates in rural areas vary by insurance status, socioeconomic status, region, race, and ethnicity.

Methods: California Cancer Registry data (2015-2019) were used to investigate the stage of diagnosis by levels of rurality for the five most common cancers. The percentage of residents in rural blocks within census tract aggregation zones was categorized into deciles up to 50%. Multivariable logistic regression was used to estimate associations with rurality, with separate models by cancer site, sex, race, and ethnicity (non-Hispanic White and Hispanic). Covariates included individual-level and zone-level factors.

Results: The percentage of late-stage cancer diagnosis was 28% for female breast, 27% for male prostate, 77% for male lung, 71% for female lung, 60% for male colorectal, 59% for female colorectal, 7.8% for male melanoma, and 5.9% for female melanoma. Increasing rurality was significantly associated with increased odds of late-stage cancer diagnosis for female breast cancer (Ptrend < 0.001), male lung cancer (Ptrend < 0.001), female lung cancer (Ptrend < 0.001), and male melanoma (Ptrend = 0.01), after adjusting for individual-level and zone-level factors. The strength of associations varied by sex and ethnicity. For males with lung cancer, odds of late-stage diagnosis in areas with >50% rural population was 1.24 (95% confidence interval, 1.06-1.45) for non-Hispanic White patients and 2.14 (95% confidence interval, 0.86-5.31) for Hispanic patients, compared with areas with 0% rural residents.

Conclusions: Increasing rurality was associated with increased odds for late-stage diagnosis for breast cancer, lung cancer, and melanoma, with the strength of associations varying across sex and ethnicity.

Impact: Our findings will inform cancer outreach to these rural subpopulations.

Background: Diet-disease association studies increasingly use dietary patterns (DP) to account for the complexity of the exposure. We assessed if a DP associated with type 2 diabetes mellitus, cardiovascular disease, and all-cause mortality is also associated with colorectal cancer.

Methods: We used reduced rank regression on 24-hour recall data to identify DPs, explaining the maximum variation in four nutrient-response variables: energy density, saturated fatty acids, free sugars, and fiber density. Cox proportional hazards models examined prospective associations between DP adherence (coded in a continuous scale as z-scores as well as in quintiles) and incident colorectal cancer. Subgroup analyses were conducted for tumor site, age, and sex.

Results: After exclusions, 1,089 colorectal cancer cases occurred in 114,443 participants over a median follow-up of 8.0 years. DP1 was characterized by increased intake of chocolate and confectionery; butter; low-fiber bread; red and processed meats; and alcohol, as well as low intake of fruits, vegetables, and high-fiber cereals. After accounting for confounders, including body mass, there were positive linear associations between DP1 and incident overall colorectal cancer (HR of quintile 5 vs. 1, 1.34; 95% confidence interval, 1.16-1.53, Ptrend = 0.005) and rectal cancer (HR of quintile 5 vs. 1, 1.58; 95% confidence interval, 1.27-1.96, Ptrend = 0.009) but not for proximal or distal colon cancers. No DP2-colorectal cancer association was observed.

Conclusions: A DP previously associated with cardiometabolic disease is also associated with incident colorectal cancer, especially rectal cancers.

Impact: These consistent associations of particular food groups with both cardiometabolic disease and this diet-related cancer strengthen the evidence base for holistic population dietary guidelines to prevent ill-health.

Background: Height and mammographic breast density are well-known risk factors for breast cancer. This study aims to investigate the association between height and mammographic density with breast cancer risk in a large population-based cohort of Korean women.

Methods: This retrospective cohort study included 4,851,115 women ages 40 and older who underwent screening mammography through the Korean National Cancer Screening Program between 2009 and 2014 and were followed up until 2016. Multivariable Cox proportional hazard models were used to estimate adjusted HRs and 95% confidence intervals (CI) for the associations among height, mammographic density, and breast cancer risk.

Results: A taller stature was associated with an increased risk of breast cancer, with women in the highest quintile of height (Q5) having a 1.54-fold (95% CI, 1.49-1.59) greater risk than those in the lowest quintile (Q1). When analyzing breast cancer risk based on height and mammographic density, women in the highest quintile for height (Q5) with extremely dense breasts had a 4.51-fold (95% CI, 4.24-4.79) greater risk than those in the lowest quintile (Q1) with almost entirely fatty breasts (Ptrend < 0.001).

Conclusions: This first study to simultaneously examine these two variables found that height and mammographic density were independently associated with breast cancer risk in this large cohort of Korean women.

Impact: Height and mammographic density can help stratify risk in screening populations for breast cancer. Careful consideration of screening strategies may be beneficial for taller women with dense breasts.

Background: Risk of early-stage lung adenocarcinoma recurrence after surgical resection is significant, and the postrecurrence median survival is approximately 2 years. Currently, there are no commercially available biomarkers that predict recurrence. In this study, we investigated whether microbial and host genomic signatures in the lung can predict recurrence.

Methods: In 91 patients with early-stage (stage IA/IB) lung adenocarcinoma with extensive follow-up, we used 16s rRNA gene sequencing and host RNA sequencing to map the microbial and host transcriptomic landscape in tumor and adjacent unaffected lung samples.

Results: Of 91 subjects, 23 had tumor recurrence over 5-year period. In tumor samples, lung adenocarcinoma recurrence was associated with enrichment in Dialister and Prevotella, whereas in unaffected lung samples, recurrence was associated with enrichment in Sphingomonas and Alloiococcus. The strengths of the associations between microbial and host genomic signatures with lung adenocarcinoma recurrence were greater in adjacent unaffected lung samples than in the primary tumor. Among microbial-host features in the unaffected lung samples associated with recurrence, enrichment in Stenotrophomonas geniculata and Chryseobacterium was positively correlated with upregulation of IL2, IL3, IL17, EGFR, and HIF1 signaling pathways among the host transcriptome. In tumor samples, enrichment in Veillonellaceae (Dialister), Ruminococcaceae, Haemophilus influenzae, and Neisseria was positively correlated with upregulation of IL1, IL6, IL17, IFN, and tryptophan metabolism pathways.

Conclusions: Overall, modeling suggested that a combined microbial/transcriptome approach using unaffected lung samples had the best biomarker performance (AUC = 0.83).

Impact: This study suggests that lung adenocarcinoma recurrence is associated with distinct pathophysiologic mechanisms of microbial-host interactions in the unaffected lung rather than those present in the resected tumor.

Background: Vitamin D deficiency is linked to poor cancer outcomes but the impact of its consequence, elevated parathyroid hormone (PTH), remains understudied. PTH receptor activation influences cancer progression in vitro, yet the effect of elevated PTH on pediatric cancer survival is unexamined.

Methods: This retrospective study examines associations between PTH, 25-OH vitamin D (25OHD), and event-free survival (EFS) and overall survival (OS) in patients with pediatric cancer. Laboratory data from 4,349 patients (0-18 years) at a tertiary pediatric cancer unit were analyzed for the highest PTH and lowest 25OHD levels at diagnosis and the following 5 years. Data on relapse, secondary malignancies, and mortality were stratified by PTH levels above/below the cohort median (47 pg/mL) and 25OHD levels ≤30 nmol/L. EFS and OS were analyzed and hazard ratios (HR) were calculated for the entire cohort and six cancer subgroups.

Results: PTH and 25OHD values were available for 1,286 patients (731 male). Higher PTH associated with inferior EFS in primary malignant brain tumors [HR, 1.80 (1.19-2.72)], embryonal malignancies [HR, 2.20 (1.1-4.43)], and lymphatic malignancies [HR 1.98 (1.05-3.72)]. Vitamin D deficiency associated with inferior EFS in embryonal malignancies [HR 2.41 (1.24-4.68)]. In a multivariate Cox model, only higher PTH remained significant for inferior EFS.

Conclusions: Elevated PTH may indicate adverse outcomes in certain pediatric cancers.

Impact: This study identifies elevated parathyroid hormone as a potential marker for poor outcomes in patients with pediatric cancer, emphasizing the need for adequate vitamin D and calcium management.