Cancer Epidemiology Biomarkers & Prevention最新文献

Background: Despite the risk of anal cancer in sexual and gender minority populations (SGM), anal cancer screening remains infrequent and inconsistent in these populations. The objective of this analysis was to identify factors associated with anal cancer screenings among sexual and gender minority populations (SGM) using the Andersen's Behavioral Model of Health Services Use.

Methods: Secondary analyses of two cross-sectional surveys from the 2020 (N=1125) and 2022 (N=630) "Pennsylvania LGBTQ Health Needs Assessment." Multiple logistic regression analyses were used to identify correlates of anal cytology screening.

Results: Average age was 37.7 (SD=13.3) and 39.7 (SD=13.6) in 2020 and 2022, respectively. Approximately 16-18% reported living with HIV. A minority of respondents reported past year screening (14.0% 2020 and 13.6% 2022). Enabling and need-based factors consistently associated with screening included STI treatment, living with HIV, PrEP use, and multiple sex partners. Robust factors associated with ever being screened were age and living with HIV.

Conclusions: Anal cytology screening is being done in Pennsylvania at a small but not insignificant rate. In accordance with existing guidelines, SGM living with HIV were most likely to be screened, but still at a low rate. Predictive factors associated with screening in this study can inform future interventions to implement guideline-specific anal cancer prevention.

Impact: Factors that reflect consistent connection to healthcare are associated with increased rates of screening via anal cytology testing, indicating there are opportunities to implement anal cancer screening as part of a larger, more comprehensive SGM-focused care pathway.

Background: In the United States (US), Epstein-Barr Virus (EBV)-associated nasopharyngeal carcinoma (NPC) disproportionately impacts Asian Americans (AA) and Native Hawaiians and other Pacific Islanders (NHPI) who have no access to screening. EBV-based screening trials in Asia have detected most cases at early stages. We sought to identify a US target population for NPC screening and hypothesized that once-lifetime screening could be cost-effective.

Methods: We obtained NPC incidence data from the SEER Asian and Pacific Islander datasets. We estimated the number needed to screen, mortality reduction, and resource utilization using a validated model and performance data from trials. Six evaluated strategies incorporated serology, nasopharyngeal swab PCR, and endoscopy or MRI.

Results: Intermediate-incidence and high-incidence populations accounted for 10.7% of US person-years yet 42.7% of cases. Anti-BNLF2b screening with selective endoscopy was the preferred strategy. In high-incidence populations, the median NNS to detect one case was 1,992, with a median of 7.12 NPC deaths averted per 100,000 screened. Screening met the willingness-to-pay threshold in all five high-incidence populations (median ICER/GDP 0.82) and among men in intermediate-incidence populations.

Conclusions: Nearly half of NPC in the US arises among the 10% with AA or NHPI ethnicity. A suitable target population for US screening trials would be men and women age 35-65 of Chinese, Sāmoan, or Southeast Asian ethnicity, or men age 35-60 of Guamanian/Chamorro, Filipino, or Native Hawaiian ethnicity. Once-lifetime anti-BNLF2b screening could be cost-effective.

Impact: These data may aid the design of US screening trials. Targeted NPC screening might mitigate health disparities.

Background: Epidemiological and laboratory-based studies have provided conflicting evidence for a role of ghrelin in colorectal cancer (CRC) development. We conducted two-sample Mendelian randomization (MR) analyses to evaluate evidence for an association of circulating ghrelin and CRC risk overall and by sex, cancer subsite and age at diagnosis.

Methods: Genetic instruments proxying plasma total ghrelin levels were obtained from a recent genome-wide association study of 54,219 participants. Summary data for CRC risk were obtained from a recent meta-analysis of several genetic consortia (up to 73,673 cases and 86,854 controls). A two-sample MR approach and several sensitivity analyses were applied.

Results: We found no evidence for an association of genetically-predicted plasma total ghrelin levels and CRC risk (0.95, 95% confidence interval: 0.81-1.12; R2 of ghrelin genetic instruments: 4.6%), with similarly null results observed when stratified by sex, anatomical subsite, and for early-onset CRC.

Conclusions: Our study suggests that plasma ghrelin levels are unlikely to have a causal relationship with overall, early-onset, and sex- and cancer subsite-stratified CRC risk.

Impact: This large-scale analysis adds to the growing body of evidence that plasma total ghrelin levels are not associated with CRC risk.

Background: Mammography is crucial for early breast cancer detection. In Latin America, Argentina faces a significant breast cancer burden, with varying mammography rates. The social factors influencing mammography practices remain unclear. This study aimed to identify the proximal and distal social determinants of this practice among Argentinean women using a multilevel approach.

Methods: This nationwide cross-sectional study included 4,924 women aged 50-70 participating in the 2018 National Risk Factor Survey of Argentina. Two-level logistic models were used to estimate measures of association (ORs) between timely mammography practice (within the last 2 years) and selected covariates (sociodemographics, proximal environment, and distal-level variables). The intraclass correlation coefficient (ICC) and proportional change in variance (PCV) were calculated.

Results: 62.8% of women underwent timely mammography. Age (OR=0.96; 95%CI 0.94-0.97), health insurance (OR=2.22; 95%CI 1.87-2.63), education (OR=2.1; 95%CI 1.74-2.64), and income (OR=1.56; 95%CI 1.23-1.97) were associated with mammography practice. Women in non-marital (OR=0.61; 95%CI 0.52-0.72) or larger households (OR=0.61; 95%CI 0.51-0.63) were less likely to have timely mammograph; living in a larger city was positively associated (OR=1.28; 95%CI 1.12-1.46). Women in provinces with higher physician density (OR=1.06; 95%CI 1.01-1.11) and lower maternal mortality ratio (OR=0.9; 95%CI 0.87-0.96) had higher chances of timely mammography. The ICC and PCV suggested that the explored healthcare indicators largely explained the macro-contextual effect.

Conclusions: Multilevel factors influenced mammography practices in Argentina. The results highlight disparities linked to sociodemographic characteristics and healthcare resources.

Impact: Efforts to address social inequalities in breast cancer screening must consider multilevel determinants, including in healthcare settings.

Background: The Hispanic population is the second largest racial/ethnic group in the US, consisting of multiple distinct ethnicities. Ethnicity-specific variations in cancer mortality may be attributed to countries of birth, so we aimed to understand differences in cancer mortality among disaggregated Hispanics by nativity (native- or foreign- born vs. US-born) over 15 years.

Methods: 228,197 Hispanic decedents (Mexican, Puerto Rican [PR], Cuban, and Central or South American) with cancer-related deaths from US death certificates (2003-2017) were analyzed. Seven cancers that contribute significantly to Hispanic male (lung and bronchus, colon and rectum, liver, prostate, and pancreas cancers) and female (lung and bronchus, liver, pancreas, colon and rectum, female breast, and ovary cancers) mortality were selected for analysis. 5-year age-adjusted mortality rates [AAMR (95% CI); per 100,000] and standardized mortality ratios [SMR (95% CI)] using foreign-born as the reference group were calculated. Joinpoint regression analysis was used to model cancer-related mortality trends.

Results: Puerto Rico-born PRs, Cuba-born Cubans, and US-born Mexicans had some of the highest cancer death rates among all the Hispanic groups. In general, foreign-born Hispanics had higher cancer mortality rates than US-born, except Mexicans. Overall, US-born and non-US-born (i.e. native- or foreign- born) Hispanic groups experienced decreasing rates of cancer deaths over the years.

Conclusions: We noted vast heterogeneity in mortality rates by nativity across Hispanic groups, a fast-growing diverse US population.

Impact: Understanding disaggregated patterns and trends in cancer burden can motivate deeper discussion around community health resources, which may improve the health of Hispanics across the US.

Background: Long-term energy balance-related factors (i.e., lifestyle and physiologic factors that influence the equilibrium between energy intake and energy expenditure over an extended period) such as body mass index (BMI) are linked to colorectal cancer risk, but their impact on colorectal cancer survival is unclear. We explored associations between these long-term energy balance-related factors and survival and examined potential differences across metabolic Warburg-subtypes.

Methods: Associations between long-term energy balance-related factors and survival in the total series of patients with colorectal cancer (n = 2,347) obtained from the prospective Netherlands Cohort Study, as well as according to Warburg-subtype (Warburg-low: n = 652, Warburg-moderate: n = 802, Warburg-high: n = 797), were investigated using Cox regression analysis.

Results: Among the long-term energy balance-related factors studied, only increasing prediagnostic BMI was associated with a borderline significant poorer overall survival in patients with colorectal cancer [HR5kg/m2, 1.07; 95% confidence interval (CI), 0.99-1.15]. Stratified analyses showed that prediagnostic weight gain (HR5kg, 1.04; 95% CI, 0.99-1.09) and potentially increased height (HR5cm, 1.04; 95% CI, 0.98-1.11) were associated with poor overall survival only in patients with Warburg-high colorectal cancer. Increasing prediagnostic BMI was associated with poor survival only in patients with Warburg-moderate colorectal cancer (colorectal cancer-specific: HR5kg/m2, 1.12; 95% CI, 0.96-1.32; overall: HR5kg/m2, 1.20; 95% CI, 1.05-1.36). No consistent patterns were observed across energy restriction proxies.

Conclusions: Maintaining a healthy prediagnostic BMI may be beneficial for colorectal cancer survival. Moreover, associations between prediagnostic BMI, weight change, early-life energy restriction, height, and colorectal cancer survival differed according to Warburg-subtypes.

Impact: Understanding the biologic pathways involved in associations between energy balance-related factors and colorectal cancer survival could help refine prevention strategies in the future.

Background: Contribution of dominance effects to cancer heritability is unknown. We leveraged existing genome-wide association data for seven cancers to estimate the contribution of dominance effects to the heritability of individual cancer types.

Methods: We estimated the proportion of phenotypic variation caused by dominance genetic effects using genome-wide association data for seven cancers (breast, colorectal, lung, melanoma, nonmelanoma skin, ovarian, and prostate) in a total of 166,772 cases and 284,824 controls.

Results: We observed no evidence of a meaningful contribution of dominance effects to cancer heritability. By contrast, additive effects ranged between 0.11 and 0.34.

Conclusions: In line with studies of other human traits, the dominance effects of common genetic variants play a minimal role in cancer etiology.

Impact: These results support the assumption of an additive inheritance model when conducting cancer association studies with common genetic variants.

Background: Filipino Americans constitute 12% and 4% of the respective populations of Hawaii and California, with a large proportion of immigrants experiencing increasing cancer rates. This study investigated the incidence of colorectal, breast, and prostate cancers by generational status in the Multiethnic Cohort.

Methods: We analyzed 10,495 Filipino Multiethnic Cohort first-, second-, and third-generation participants, in which 26.8% were of mixed race and ethnicity. Linkage to statewide cancer registries identified 375 breast, 249 colorectal, and 436 prostate cancer incident cases. Cox models were used to calculate HRs and 95% confidence intervals (CI) for the association between generational status and cancer incidence. Models were adjusted for age at cohort entry and cancer-specific covariates that were chosen based on stepwise regression.

Results: Compared with the first generation, colorectal cancer showed a significantly higher incidence in the second and third generations with respective HRs of 1.43 (95% CI, 1.04, 1.98) and 1.76 (95% CI, 1.29, 2.38). This association was attenuated after adjustment for relevant covariates. Breast cancer incidence was elevated in the third versus first generation (HR = 1.29; 95% CI, 1.01, 1.63) even in the fully adjusted model, whereas little difference was observed for prostate cancer.

Conclusions: In this prospective study, we found differences in incidence by generational status, specifically colorectal cancer among men and female breast cancer.

Impact: Understanding behavioral changes due to acculturation is warranted to mitigate cancer risks in migrant populations.

Background: Sociodemographic disparities in traditional breast cancer treatment receipt in nonpublicly funded healthcare systems are well documented. This study investigated trastuzumab receipt by sociodemographic factors within a female, HER2+ breast cancer population in England's publicly funded National Health Service.

Methods: The English national population-based cancer registry and linked Systemic Anti-Cancer Therapy database identified 36,985 women with HER2+ invasive breast cancer diagnosed between January 1, 2012 and December 31, 2017. Multivariable logistic regression determined the likelihood of trastuzumab receipt in early and metastatic disease by the deprivation category of area of residence and other sociodemographic characteristics.

Results: Early-stage trastuzumab receipt followed a socioeconomic gradient. Women residing in the most deprived areas were 10% less likely to receive trastuzumab [multivariable OR 0.90; 95% confidence interval (CI), 0.83-0.98] compared with women residing in the least deprived areas. In both early and metastatic disease, trastuzumab receipt was less likely in older women with more comorbidities, estrogen receptor-positive disease, and who were not discussed at a multidisciplinary team meeting.

Conclusions: Despite the provision of free care at the point of delivery in England, sociodemographic disparities in early-stage HER2+ trastuzumab receipt occur. Further research determining how inequities contribute to disparities in outcomes is warranted to ensure optimized trastuzumab use for all.

Impact: Fair access to novel cancer treatments regardless of place of residence, sociodemographic characteristics, and/or cancer stage requires prioritization in future cancer improvement policies. See related In the Spotlight, p. 1259.

Background: Periodontal disease and DNA methylation markers have separately been associated with lung cancer risk. Examining methylation levels at genomic regions previously linked to periodontal disease may provide insights on the link between periodontal disease and lung cancer.

Methods: In a nested case-control study drawn from the CLUE II cohort, we measured DNA methylation levels in 208 lung cancer cases and 208 controls. We examined the association between 37 DNA-methylated 5'-C-phosphate-G-3' (CpG) sites at three genomic regions, homeobox 4 (HOXA4), zinc finger protein (ZFP57), and a long noncoding RNA gene located in Chr10 (ENSG00000231601), and lung cancer risk.

Results: Statistically significant associations with lung cancer risk were observed for all 14 CpG sites from HOXA4 (OR ranging 1.41-1.62 for 1 SD increase in the DNA methylation level, especially within 15 years) and 1 CpG site on gene ENSG00000231601 (OR = 1.34 for 1 SD increase in the DNA methylation level). Although CpG sites on gene ZFP57 were not associated with lung cancer risk overall, statistically significant inverse associations were noted for six CpG sites when restricting follow-up to 15 years (OR = 0.73-0.77 for 1 SD increase in the DNA methylation level).

Conclusions: Key methylation levels associated with periodontal disease are also associated with lung cancer risk. For both HOXA4 and ZFP57, the associations were stronger within 15 years of follow-up, which suggest that, if causal, the impact of methylation is acting late in the natural history of lung cancer.

Impact: Identifying biological pathways that link periodontal disease and lung cancer could provide new opportunities for lung cancer detection and prevention.