Cancer Epidemiology Biomarkers & Prevention最新文献

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: 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.

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: Guidelines informing chemotherapy regimen selection are based on clinical trials with participants who do not necessarily represent general populations with breast cancer. Understanding who receives nonguideline regimens is important for understanding real-world chemotherapy administration and how it relates to patient outcomes.

Methods: Using data from the Optimal Breast Cancer Chemotherapy Dosing (OBCD) study, based at Kaiser Permanente Northern California (2006-2019) and Kaiser Permanente Washington (2004-2015), we use logistic regression to examine the associations between patient characteristics and receipt of nonguideline chemotherapy regimens among 11,293 women with primary stage I to IIIA breast cancer receiving chemotherapy.

Results: The use of nonguideline regimens was strongly associated with several factors, including older age [≥80 vs. 18-39 years: OR, 5.25; 95% confidence interval (CI), 3.06-9.00; P-trend = 0.002] and HER2 status (HER2+ vs. HER2-: OR, 3.44; 95% CI, 3.06-3.87) and was less likely in women with larger tumor size (>5 cm vs. 0.1 to ≤0.5 cm: OR, 0.56; 95% CI, 0.36-0.87; P-trend = 0.01) and diagnosed in later years (2012-2019 vs. 2005-2011: OR, 0.80; 95% CI, 0.71-0.90). Factors associated varied by type of nonguideline regimens. For example, women with comorbidity and older age were more likely to receive nonguideline drug combinations in particular, whereas women with larger tumor size were less likely to receive nonguideline administration schedules.

Conclusions: Nonguideline chemotherapy regimens are more likely in certain patient populations.

Impact: These associations highlight that vulnerable patient populations may be less likely to receive guideline care, and thus, real-world studies are essential for understanding how the use of nonguideline regimens impacts patient outcomes in these groups.

Background: We examined the association between late-stage diagnosis and individual- and community-level sociodemographic and socioeconomic characteristics among patients with pediatric Hodgkin lymphoma and rhabdomyosarcoma (RMS).

Methods: We obtained Children's Oncology Group data from 1999 to 2021 including summary stage [local (L), regional (R), and distant (D)], tumor subtype, demographics, and ZIP Code at diagnosis. We linked ZIP Codes to county-level redlining scores (C, D = greatest redlining), the Child Opportunity Index, and measures of segregation (racial dissimilarity indices). Logistic regressions calculated odds ratios for late-stage diagnosis and by race within tumor subtype.

Results: In total, 5,956 patients with Hodgkin lymphoma and 2,800 patients with RMS were included. Late-stage diagnosis of Hodgkin lymphoma was correlated with Black race [ORDistant(D) vs. regional/local (R&L) = 1.38 (1.13-1.68)], being uninsured [ORD vs. R&L = 1.38 (1.09-1.75)], and subtype [nodular sclerosis vs. Other Hodgkin lymphoma: ORD vs. R&L = 1.64 (1.34-2.01), Untyped: ORD vs. R&L = 1.30 (1.04-1.63)]. Late-stage RMS was correlated with bilingual households [ORDistant/regional(D&R) vs. local(L) = 2.66 (1.03-6.91)] and tumor type [alveolar vs. embryonal ORD vs. R&L = 6.16 (5.00-7.58)]. Community-level factors associated with late-stage Hodgkin lymphoma were greater Black (OR80-100% = 1.83; 95% CI = 1.11-3.02) and Hispanic (OR60-79% = 1.30; 95% CI = 1.05-1.60) dissimilarity indices. Late-stage diagnosis for RMS was associated with more redlined census tracts within counties (OR = 1.54; 95% CI = 1.02-2.35) and low/very low Child Opportunity Index (OR = 1.21; 95% CI = 1.02-1.45).

Conclusions: Novel markers of community deprivation, such as redlining and racial segregation, were correlated with cancer outcomes for children with Hodgkin lymphoma and RMS in this first disparities study using Children's Oncology Group registries.

Impact: The interplay of multilevel risk factors provides important consideration for efforts to improve early detection of pediatric cancer diagnosis.

Background: The role of adult adiposity in young-onset breast cancer (YOBC) subtype risk is not well understood.

Methods: In this population-based case(n=1812)-control(n=1381) study of invasive YOBC (aged <50 years), cases were identified from the Los Angeles County and Metropolitan Detroit SEER registries, 2010-2015. Area-based, frequency-matched controls were sampled from the 2010 Census. General adiposity (body mass index (BMI)) and central adiposity (waist circumference (WC), waist-to-height ratio (WHtR)) across adulthood and covariates were collected from in-person interviews and measurements. Odds ratios (ORs) and 95% confidence intervals (CIs) for adiposity and YOBC tumor subtypes (i.e., luminal A, luminal B, HER2+, triple negative (TN)) were calculated, overall and by parity, using multivariable weighted logistic regression.

Results: Obese young adult BMI was inversely associated with luminal A YOBC (OR=0.35, 95% CI 0.16-0.79); other subtype associations were non-significant. Similarly, adult overweight and obese BMIs were inversely associated with luminal A (respectively OR=0.66, 95% CI 0.48-0.91 and OR=0.59, 95% CI 0.46-0.87), but not other subtypes. Conversely, larger WC was associated with higher odds of luminal B and TN YOBC (respectively OR=1.48, 95% CI 1.01-2.15 and OR=2.48, 95% CI 1.52-3.88), but not other subtypes (with similar results for WHtR); highest odds were among parous women.

Conclusions: Findings show greater general adult adiposity is associated with reduced odds of luminal A YOBC, while greater central adiposity is associated with increased odds of luminal B and TN YOBC, particularly among parous women.

Impact: Additional studies of central adiposity and YOBC subtype risk, especially incorporating pregnancy history, are warranted.

Background: Body composition may be related to survival in patients with clear-cell renal cell carcinoma (ccRCC), but studies have not simultaneously considered adipose and muscle tissue quantity and radiodensity.

Methods: We analyzed data from 1,022 patients with ccRCC who underwent nephrectomy between 2000 and 2020 at Memorial Sloan Kettering Cancer Center. Skeletal muscle, visceral adipose tissue, and subcutaneous adipose tissue indexes (cm2/m2) and radiodensities [Hounsfield units (HU)] were assessed from noncontrast presurgical CT scans; clinical and demographic characteristics were available from the time of surgery. HRs and confidence intervals were estimated for overall (OS) and disease-free survival (DFS) through March 2023 in multivariable models that simultaneously accounted for all body composition measures.

Results: The median age of the patients was 58 years, 69% were male, and 90% were White. There were 169 OS events over 8,392 person-years and 253 DFS events over 7,753 person-years of follow-up. In adjusted analyses, poor OS was associated with lower skeletal muscle radiodensity [-10 HU, HR (95% confidence interval), 1.37 (1.05-1.77)] and greater visceral adipose tissue radiodensity [+10 HU, 1.66 (1.06-2.59)], with similar findings for DFS. Poor survival was also associated with greater visceral adipose tissue index [+40 cm2/m2, OS: 1.32 (0.97, 1.79); DFS: 1.33 (1.04, 1.71)]. Associations with skeletal muscle radiodensity were limited to patients with stage 1/2 disease.

Conclusions: Radiodensities of skeletal muscle and visceral adipose tissues may be novel presurgical prognostic factors for patients with ccRCC.

Impact: The findings underscore the importance of evaluating the full range of body composition features simultaneously in multivariable models.

Liver cancer, the sixth most frequently occurring cancer in the world and the third most common cause of cancer mortality, has wide geographical variation in both incidence and mortality rates. At the end of the 20th century, incidence rates began declining in some high-rate areas and increasing in some lower-rate areas. These trends were undoubtedly driven by the shifting contributions of both well-established and more novel risk factors. While notable strides have been made in combating some major risk factors, such as hepatitis B virus and hepatitis C virus, the emergence of metabolic conditions as important drivers of liver cancer risk indicates that much work remains to be done in prevention. As liver cancer is strongly associated with economic and social deprivation, research, early-diagnosis, and treatment among disadvantaged populations are of paramount importance.

Background: The incorporation of breast density and a polygenic risk score (PRS) into breast cancer risk prediction models can alter previously communicated risk estimates. Previous research finds that risk communication does not usually change personal risk appraisals. This study aimed to examine how women from the Family History Risk (FH-Risk) study appraise their breast cancer risk following communication of an updated risk estimate.

Methods: In the FH-Risk study 323 women attended a consultation to receive an updated breast cancer risk estimate. A subset (n=190) completed a questionnaire, assessing their subjective breast cancer risk appraisals, satisfaction with the information provided and cancer related worry. One hundred and three were notified of a decrease risk, 34 an increase and 53 an unchanged risk.

Results: Women's subjective risk appraisals were in line with the updated risk estimates provided, with age, a PRS and breast density explaining most of the variance in these appraisals. Those notified of an increased risk demonstrated higher subjective risk perceptions compared to those whose risk remained unchanged or decreased.

Conclusions: Women's subjective breast cancer risk appraisals are amenable to change following updated risk feedback, with new information breast density and a PRS accepted and integrated into existing risk appraisals. Trust in the service, the analogies and visual communication strategies used may have positively influenced the integration of this new information.

Impact: Further research is warranted to assess whether similar patterns emerge for other illnesses and in different clinical contexts to determine the best strategies for communicating updated risk estimates.

Background: Higher magnesium intake was linked to a lower risk of hepatocellular carcinoma (HCC). However, the relationship between blood magnesium level and HCC has not been fully characterized, especially among patients with liver cirrhosis who are at a higher risk for HCC.

Methods: In the Mass General Brigham Biobank, we developed a new prospective cohort of 1,430 patients with liver cirrhosis without liver cancer history using the validated International Classification of Diseases codes. We used Cox proportional hazards models to generate hazard ratios (HRs) with 95% confidence intervals (CI) for incident HCC and used generalized estimating equations to compare changes in liver biomarkers according to baseline blood magnesium, adjusting for age, sex, race, lifestyles, body mass index, type 2 diabetes, model for end-stage liver disease score, and hepatitis infection.

Results: During a median follow-up period of 4.26 years, 109 patients developed HCC. Magnesium deficiency (<1.70 mg/dL; N = 158) was associated with a higher risk of HCC (HR = 1.93; 95% CI, 1.12-3.30) compared with magnesium sufficiency (≥1.70 mg/dL; N = 1282). This association remained robust in the 1-year lag analysis (HR = 2.18; 95% CI, 1.11-4.28) and in sensitivity analysis excluding patients with alcoholic liver disease (HR = 2.41; 95% CI, 1.23-4.74). Magnesium in the lowest quartile was associated with a faster increase in alanine transaminase (β = 4.35; 95% CI, 1.06-7.63), aspartate aminotransferase (β = 6.46; 95% CI, 0.28-12.6), direct bilirubin (β = 0.18; 95% CI, 0.01-0.35), and total bilirubin (β = 0.21; 95% CI, 0.03-0.39), compared with the highest quartile.

Conclusions: Lower blood magnesium level is associated with higher HCC risk and unfavorable liver biomarker changes.

Impact: If confirmed, our findings may potentially enable better identification of high-risk patients for HCC and inform better management strategies for liver cirrhosis.