Cancer Epidemiology Biomarkers & Prevention最新文献

Background: The sensitivity of a cancer screening biomarker to detect prevalent preclinical cancer drives screening benefit. Studies estimate sensitivity at different points in the biomarker development process. We examine how closely these estimates reflect the sensitivity to detect preclinical cancer (preclinical sensitivity).

Methods: We posit that preclinical sensitivity is inversely proportional to the preclinical sojourn time. We simulate studies and estimates of sensitivity corresponding to the Early Detection Research Network's Phases of Biomarker Development. Sensitivity estimates based on clinically diagnosed cases (phase II, clinical sensitivity), archived-sample studies (phase III, archived-sample sensitivity), and prospectively screened cohorts (phases IV and V, prospective empirical sensitivity) are defined and compared against the corresponding expected preclinical sensitivity.

Results: Clinical sensitivity is generally optimistic. Archived-sample sensitivity is optimistic near clinical diagnosis but may be pessimistic at longer look-back intervals, with bias also dependent on test specificity. Prospective empirical sensitivity is optimistic when the sojourn time is long relative to the screening interval. Bias in prospective empirical sensitivity also depends on the frequency and accuracy of confirmation testing following a positive screening test.

Conclusions: Sensitivity estimates from different phases of biomarker development should be distinguished and labeled accordingly to facilitate a realistic assessment of diagnostic performance and prediction of potential benefit.

Impact: Our study highlights the need for clearer terminology to describe the sensitivity of cancer early detection biomarkers. We introduce new labels, explain biases in sensitivity estimates, and advocate for improved communication to enhance understanding of diagnostic test performance.

Background: This study aims to assess the population attributable fraction (PAF) of diabetes on the gastrointestinal cancers overall and by specific cancer sites.

Methods: This study analyzed healthcare data from Taiwan (2006-2019) for 2,362,587 patients with and without diabetes. Gastrointestinal cancers were identified via cancer registry data. Poisson regression calculated incidence rate ratios (IRR) and 95% confidence intervals (CI), with propensity score-matched patients without diabetes as the reference. PAFs estimated cancer incidence attributable to diabetes by sites.

Results: 80,186 patients with diabetes (mean age, 63.3 years; 47.3% women) were matched with 152,323 patients without diabetes (62.7 years; 48.0% women). By the end of 2021, 2,659 of 80,186 patients with diabetes (incidence rate: 3.89 per 1,000 person-years) developed gastrointestinal cancers compared with 4,150 of 152,323 (incidence rate: 3.04 per 1,000 person-years) patients without diabetes. Diabetes was associated with a higher risk of gastrointestinal cancers (adjusted IRR of 1.24, 95% CI, 1.18-1.30; PAF: 4.4%, 95% CI, 3.1%-5.8%). The increased risk was primarily driven by pancreatic cancer (adjusted IRR: 1.77, 95% CI, 1.51-2.09; PAF: 12.9%, 95% CI, 7.9%-18.6%) and colorectal cancer (adjusted IRR: 1.28, 95% CI, 1.17-1.39; PAF: 5.1%, 95% CI, 3.0%-7.5%), with a borderline association for liver cancer (adjusted IRR: 1.08, 95% CI, 1.00-1.17; PAF: 1.5%, 95% CI, -0.3% to 3.5%).

Conclusions: Diabetes is associated with an increased risk of overall gastrointestinal cancers, largely attributable to pancreatic and colorectal cancers.

Impact: Integrating cancer prevention into the objectives of optimal diabetes management is important, especially for cancers with limited screening options.

Background: Approximately 5% of patients with breast cancer have a rare pathogenic germline genetic variant that is associated with increased breast cancer risk. Mutations in more than 12 genes have been associated with hereditary breast cancer risk, many of which are involved in genome stability pathways, including DNA double-strand break (DSB) repair. We hypothesized that carriers of DSB repair-related pathogenic variants (PV) may have a distinct tumor immune environment that differs from that of noncarriers.

Methods: We utilized tumor transcriptome data from 559 participants with invasive breast cancer from the Nurses' Health Studies and Nurses' Health Studies II to infer immune-related gene expression signatures and immune cell abundance.

Results: Thirty-three (5.9%) individuals had germline DSB repair-related PVs in one or more of the following genes: ATM, BARD1, BLM, BRCA1, BRCA2, BRIP1, CHEK2, FANCC, FANCM, NBN, PALB2, RAD50, RAD51C, and/or RECQL. In covariate-adjusted analyses, DSB repair-related PV carrier status was positively associated with both a STAT1 signature (standardized β = 0.59; P = 3.5 × 10-3) and inferred M1 macrophage infiltration (standardized β = 0.56; P = 1.4 × 10-3). Furthermore, these immune features correlated with other features related to tumor IFN response signaling, suggesting that this enrichment is occurring in an inflammatory context.

Conclusions: These results indicate that breast tumors of DSB repair-related PV carriers have distinct immune features, which may have therapeutic implications in this high-risk population.

Impact: These results support further characterization of macrophage characteristics and abundance in the breast tumor microenvironment of DSB repair-related PV carriers.

Background: Although colorectal cancer survival rates are improving, the risk of incident type 2 diabetes mellitus (T2D) among Asian, Native Hawaiian, and Pacific Islander (ANHPI) ethnic groups is poorly understood. This study aims to identify high-risk groups and quantify the risk across different periods.

Methods: Using the SEER-Medicare database, colorectal cancer survivors who were ANHPI were matched to non-Hispanic White (NHW) survivors at a ratio of 1:3. Multivariable Cox regression models computed HRs and 95% confidence intervals (CI) for incident T2D.

Results: The study included 6,463 NHW and 2,901 ANHPI colorectal cancer survivors diagnosed between 2000 and 2017. Among them, 715 NHW and 484 ANHPI developed T2D during 39,097 and 10,769 person-years of follow-up, respectively. ANHPI colorectal cancer survivors had an elevated T2D risk compared with NHW across all follow-up periods (HRoverall: 1.84, 95% CI, 1.51-2.25; HR1-5 years: 1.83, 95% CI, 1.45-2.30). Southeast and East Asians demonstrated the highest T2D risks. Colon cancer was linked to early postdiagnosis T2D risk, whereas rectal cancer was associated with later risk. No significant association was observed for Native Hawaiians and Pacific Islanders.

Conclusions: ANHPI colorectal cancer survivors face a greater risk of T2D, particularly among Southeast and East Asians. These findings highlight the need for evidence-based survivorship strategies to prevent T2D and reduce ethnic disparities.

Impact: This is the first study to examine T2D risk among ANHPI colorectal cancer survivors, providing critical insights to inform tailored diabetes prevention and survivorship care.

Background: Consistent evidence supports a reduction in breast cancer risk with a high healthy lifestyle index (HLI) score; however, this relationship has not been well studied in multiethnic populations.

Methods: Within the multiethnic cohort study, we followed 65,561 African American, Japanese American, Latina, Native Hawaiian, and White postmenopausal women for incident invasive breast cancer (n = 4,555, mean 19.2 years). The HLI summed seven components with higher scores assigned to healthier behaviors: diet quality, physical activity, sedentary behavior, smoking status, alcohol consumption, body mass index, and sleep duration. Multivariable Cox proportional hazards models estimated adjusted HRs (aHR) and 95% confidence intervals (CI) for associations between the HLI score [continuous and tertiles (T)] and breast cancer risk overall, stratified by race and ethnicity and hormone receptor status. Multiplicative interaction by race and ethnicity (P-int) and heterogeneity of effect by hormone receptor status (P-het) were assessed by the Wald test.

Results: Higher HLI scores were associated with reduced postmenopausal breast cancer risk [aHRcont: 0.95 (95% CI, 0.94-0.97), P < 0.0001; aHRT2vsT1: 0.92 (95% CI, 0.85-0.99), aHRT3vsT1: 0.81 (95% CI, 0.75-0.87), P-trend < 0.01] with similar risk reductions observed across racial and ethnic groups (P-trend ≤ 0.05; P-int = 0.96). Similar findings were observed with hormone receptor-positive breast cancer (overall: P-trend < 0.01; P-int = 0.90); no significant associations were observed with hormone receptor-negative breast cancer (P-trend > 0.05; P-int = 0.64; P-het = 0.79).

Conclusions: Higher HLI scores are associated with breast cancer risk reductions overall by race and ethnicity and hormone receptor status.

Impact: Engaging in healthy lifestyle behaviors may reduce breast cancer risk among a multiethnic population of postmenopausal women. See related In the Spotlight, p. 833.

Background: Skin cancers are the third most common cancer worldwide, with incidence increasing. Metabolic syndrome (MetS) is a cluster of metabolic abnormalities strongly associated with the development of cardiovascular disease. More than one in five individuals have MetS, and it is linked with at least 14 different cancers. This study aimed to investigate whether MetS is a risk factor for skin cancer.

Methods: A prospective cohort study was conducted in the UK Biobank. The association between MetS and skin cancer was investigated using multivariable Poisson regression. To investigate causality, a two-sample Mendelian randomization (MR) study was conducted using summary-level genome-wide association study data from the UK Biobank (MetS) and FinnGen (skin cancer).

Results: A total of 467,919 participants were included; 26.7% had MetS. Follow-up was for up to 10.8 years. MetS showed a moderately sized protective effect on basal-cell carcinoma, whereas the effect for squamous cell carcinoma and malignant melanoma crossed the null. Overall, MR found there was some weak evidence for increased odds of skin cancer in those with MetS [OR = 1.07 (95% confidence interval: 1.01, 1.14)].

Conclusions: The observational study identifies a moderately sized protective effect of MetS on basal-cell carcinoma with MR evidence suggesting a weak causal effect in the opposite direction.

Impact: This study has found little-to-no effect of MetS on skin cancer despite links between MetS and at least 14 other cancers.

Background: Few studies examine biomarkers of exposure to vaping and tobacco products among youth. We compared biomarkers for toxicants between youth who vape, smoke, "dual-use", or neither.

Methods: Participants ages 16 to 19 years in Canada, England, and the United States completed surveys and self-collected urine samples between September 2019 and January 2022 (N = 364). Urine was tested for metabolites of tobacco-specific nitrosamine NNK (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone) and six volatile organic compounds. Regression models examined differences in biomarker concentrations by past-week tobacco smoking and vaping, adjusting for creatinine, age, sex, country, and cannabis use.

Results: Compared with no vaping/smoking, exclusive vaping was associated with similar exposure to acrolein and acrylonitrile but higher exposure to toluene (P = 0.04) and acrylamide (P = 0.034, only in sensitivity analysis using past 24-hour measure). Compared with dual use or exclusive smoking, exclusive vaping was associated with lower exposure to NNK, acrolein, acrylamide, and acrylonitrile (P ≤ 0.01) but higher toluene exposure than dual use (P = 0.012). Exposure was similar for dual-use and exclusive smoking. Benzene and xylene biomarkers were detected in <5% and not compared. Among those smoking, NNK exposure was higher in the United States (geometric mean = 25.4 pg/mg creatinine) versus Canada (16.1 pg/mg; P = 0.006) and England (14.1 pg/mg; P = 0.018).

Conclusions: Youth exclusively vaping had similar exposure as no vaping/smoking except for two volatile organic compounds and lower exposure than smoking or dual use except toluene. Higher NNK levels among US youth who smoke likely reflect differences in tobacco blend.

Impact: Findings are generally consistent with literature indicating lower toxicant exposure from vaping versus smoking but elevated exposure versus no use for some.

Background: Ovarian high-grade serous carcinomas (HGSC) comprise four distinct molecular subtypes based on mRNA expression patterns, with differential survival. Understanding risk factor associations is important to elucidate the etiology of HGSC. We investigated associations between different epidemiologic risk factors and HGSC molecular subtypes.

Methods: We pooled data from 11 case-control studies with epidemiologic and tumor gene expression data from custom NanoString CodeSets developed through a collaboration within the Ovarian Tumor Tissue Analysis consortium. The PrOTYPE-validated NanoString-based 55-gene classifier was used to assign HGSC gene expression subtypes. We examined associations between epidemiologic factors and HGSC subtypes in 2,070 cases and 16,633 controls using multivariable-adjusted polytomous regression models.

Results: Among the 2,070 HGSC cases, 556 (27%) were classified as C1.MES, 340 (16%) as C5.PRO, 538 (26%) as C2.IMM, and 636 (31%) as C4.DIF. The key factors, including oral contraceptive use, parity, breastfeeding, and family history of ovarian cancer, were similarly associated with all subtypes. Heterogeneity was observed for several factors. Former smoking [OR = 1.25; 95% confidence interval (CI) = 1.03, 1.51] and genital powder use (OR = 1.42; 95% CI = 1.08, 1.86) were uniquely associated with C2.IMM. History of endometriosis was associated with C5.PRO (OR = 1.46; 95% CI = 0.98, 2.16) and C4.DIF (OR = 1.27; 95% CI = 0.94, 1.71) only. Family history of breast cancer (OR = 1.44; 95% CI = 1.16, 1.78) and current smoking (OR = 1.40; 95% CI = 1.11, 1.76) were associated with C4.DIF only.

Conclusions: This study observed heterogeneous associations of epidemiologic and modifiable factors with HGSC molecular subtypes.

Impact: The different patterns of associations may provide key information about the etiology of the four subtypes.

Background: The tumor immunosurveillance theory supports that allergic conditions could decrease cancer risk. However, observational evidence yielded inconsistent results for the association between allergic diseases and colorectal cancer risk. We used Mendelian randomization (MR) to examine potential causal associations of allergies with the risk of overall and early-onset colorectal cancer.

Methods: Genome-wide association study summary statistical data were used to identify genetic variants associated with allergic diseases (Nvariants = 65) and individual allergic conditions (asthma, hay fever/allergic rhinitis, and eczema). Using two-sample MR, we examined these variants in relation to incident overall (Ncases = 52,775 cases) and early-onset colorectal cancer (Ncases = 6,176). The mediating role of white blood cells was examined using multivariable MR.

Results: In inverse-variance-weighted models, genetic liability to allergic diseases was inversely associated with overall {OR per log (odds) = 0.90 [95% confidence interval (CI), 0.85-0.96]; P < 0.01} and early-onset colorectal cancer [OR = 0.83 (95% CI, 0.73-0.95); P = 0.01]. Similar inverse associations were found for hay fever/allergic rhinitis or eczema, whereas no evidence of association was found between liability to asthma-related phenotypes and colorectal cancer risk. Multivariable MR adjustment for eosinophils weakened the inverse associations for liability to allergic diseases for overall [OR = 0.96 (95% CI, 0.89-1.03); P = 0.26] and early-onset colorectal cancer [OR = 0.86 (95% CI, 0.73-1.01); P = 0.06].

Conclusions: Our study supports a potential causal association between liability to allergic diseases, specifically hay fever/allergic rhinitis or eczema, and colorectal cancer, possibly at least in part mediated via eosinophil counts.

Impact: Our results provide evidence that allergic responses may also have a role in immunosurveillance against colorectal cancer.

Background: Alcohol is a modifiable risk factor for several types of cancer, though awareness of this link is often found to be low among the US population. The current study investigated beliefs about alcohol as a cancer risk factor among Spanish-preferring Americans, specifically for different types of alcoholic beverages (e.g., beer, liquor, and wine).

Methods: We analyzed data from a national survey of US adults who prefer speaking Spanish, comparing their awareness of alcohol's link to cancer with the general population and Hispanic respondents in the Health Information National Trends Survey (HINTS) 5 Cycle 4 dataset.

Results: Awareness among Spanish-speaking adults was lower (wine: 8.2%, beer: 18.3%, and liquor: 28.4%) than all HINTS respondents (wine: 20.3%, beer: 24.9%, and liquor: 31.2%) and specifically the Hispanic HINTS respondents (wine: 18.3%, beer: 22.4%, and liquor: 32.2%). Statistically significant differences were found for wine and beer compared with the general population and for wine compared with Hispanic respondents. Higher media literacy correlated with increased awareness, particularly for beer, whereas eHealth literacy showed an inverse relationship. Recent immigrants demonstrated greater awareness than long-term residents. Gender, insurance status, cancer history, and information-seeking behaviors predicted differential awareness.

Conclusions: Awareness of the alcohol-cancer link among Spanish-preferring adults in the United States is below the national average, with factors such as media literacy, eHealth literacy, demographics, and length of US residency associated with this awareness.

Impact: The study underscores the need for culturally adapted health communication strategies to improve knowledge of alcohol as a cancer risk factor among Spanish-preferring Americans.