Intrahepatic (ICC) and extrahepatic (ECC) cholangiocarcinomas are rare tumors that arise from the epithelial cells of the bile ducts, and the etiology of both cancer types is poorly understood. Thus, ...we utilized the Surveillance, Epidemiology, and End Results (SEER)-Medicare resource to examine risk factors and novel preexisting medical conditions that may be associated with these cancer types.
Between 2000 and 2011, 2,092 ICC and 2,981 ECC cases and 323,615 controls were identified using the SEER-Medicare database. Logistic regression was used to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI).
Non-alcoholic fatty liver disease was associated with approximately 3-fold increased risks of ICC (OR = 3.52, 95% CI: 2.87-4.32) and ECC (OR = 2.93, 95% CI: 2.42-3.55). Other metabolic conditions, including obesity and type 2 diabetes, were also associated with increased risks of both cancer types. Smoking was associated with a 46% and 77% increased ICC and ECC risk, respectively. Several autoimmune/inflammatory conditions, including type 1 diabetes and gout, were associated with increased risks of ICC/ECC. As anticipated, viral hepatitis, alcohol-related disorders, and bile duct conditions were associated with both cancer types. However, thyrotoxicosis and hemochromatosis were associated with an increased risk of ICC but not ECC, but did not remain significantly associated after Bonferroni correction.
In this study, risk factors for ICC and ECC were similar, with the exceptions of thyrotoxicosis and hemochromatosis. Notably, metabolic conditions were associated with both cancer types. As metabolic conditions are increasing in prevalence, these could be increasingly important risk factors for both types of cholangiocarcinoma.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
15% of US adults have gallstones, most of which are clinically "silent". Several studies show that menopausal hormone therapy (MHT) increases symptomatic gallstones and cholecystectomy risk. MHT use ...may be contraindicated in women with gallstones and population studies may be biased by "confounding by contraindication" while the true association between MHT and gallstones remains underestimated. We sought to examine whether MHT use was associated with asymptomatic gallstones using instrumental variable (IV) analysis to account for confounding by contraindication. We used 2018 postmenopausal women from the Third National Health and Nutrition Examination Survey to estimate associations of MHT use with asymptomatic gallstones. A traditional logistic regression analysis was compared to instrumental variable (IV) analysis to account for confounding by contraindication. 12% of women with asymptomatic gallstones and 25% of women without gallstones were current MHT users (P < 0.001). The traditional analysis suggested a decreased odds of asymptomatic gallstones in current versus never users (OR 0.58, 95% CI 0.37, 0.89), but increased odds (OR 1.51, 95% CI 0.44, 5.16) in the IV analysis. The traditional analysis consistently underestimated the odds of asymptomatic gallstones with MHT use compared to the IV analysis. Accounting for confounding by contraindication, we found a suggestive, though imprecise, positive association between MHT use and asymptomatic gallstones among postmenopausal women. Failure to consider contraindication can produce incorrect results.
Background and Aims
Gallbladder cancer (GBC) has a female predominance, whereas the other biliary tract cancers (BTCs) have a male predominance, suggesting that sex hormones may be involved in ...carcinogenesis. We sought to evaluate the association between menopausal hormone therapy (MHT) and the risk of BTC in women.
Approach and Results
This nested case‐control study was conducted in the UK Clinical Practice Research Datalink. Cases diagnosed between 1990 and 2017 with incident primary cancers of the gallbladder (GBC), cholangiocarcinoma (CCA), ampulla of Vater (AVC), and mixed type were matched to 5 controls on birth year, diagnosis year, and years in the general practice using incidence density sampling. Conditional logistic regression was used to calculate ORs and 95% CIs for associations between MHT use and BTC type. The sample consisted of 1,682 BTC cases (483 GBC, 870 CCA, 105 AVC, and 224 mixed) and 8,419 matched controls with a mean age of 73 (SD, 11) years. Combined formulations (estrogen‐progesterone) were associated with an increased GBC risk (OR, 1.97; 95% CI, 1.08, 3.59). Orally administered MHT was associated with an increased GBC risk (OR, 2.28; 95% CI, 1.24, 4.17). Estrogen‐only formulations (OR, 0.59; 95% CI, 0.34, 0.93) and cream or suppository administrations (OR, 0.57; 95% CI, 0.34, 0.95) were associated with decreased CCA risk. The number of prescriptions, dose, duration of use, and time since last use were not associated with GBC or CCA risk. MHT use was not associated with risk of AVC or mixed cancer.
Conclusions
Combination MHT formulations and oral administrations were associated with increased GBC risk, whereas estrogen‐only formulations were associated with a lower CCA risk. MHT formulation and administration should be carefully considered when prescribing.
Background Biliary tract cancer (BTC) includes intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma, gallbladder cancer, and ampulla of Vater cancer (AVC). Although BTC is rare in ...the US, incidence is increasing and elevated in certain populations. This study examined BTC epidemiology in the US by age, sex, race/ethnicity, geographic region, and anatomic site. Methods BTC incidence, prevalence, mortality, and survival from 2001 to 2015 were evaluated using the National Cancer Institute's Surveillance, Epidemiology, and End Results Program and the Centers for Disease Control and Prevention's National Program of Cancer Registries databases. Incidence and mortality rates were calculated and reported as age-standardized rates. Data were assessed by age, anatomic sites, geographic region, and race/ethnicity, and a joinpoint regression model was used to predict trends for age-adjusted BTC incidence and mortality rates. Results BTC incidence increased during the study period (annual percent change = 1.76, 95% confidence interval 1.59-1.92), with the highest increase in ICC (6.65 6.11-7.19). Incidence of unspecified BTC initially increased but has recently begun to drop. Hispanic, Asian/Pacific Islander, Black, or American Indian/Alaska Native race/ethnicity was associated with higher BTC mortality rates than White race/ethnicity. Patients with ICC had the highest mortality rate (age-standardized rate = 1.87/100,000 person-years 1.85-1.88). Five-year survival was 15.2% for all BTC, ranging from 8.5% (ICC) to 34.5% (AVC), and patients with distant disease at diagnosis had lower survival (3%) compared with those with regional (19.1%) or locally advanced disease (31.5%). Conclusions BTC incidence increased, survival was low across all subtypes, and mortality was greatest in patients with ICC. This underscores the serious, increasing unmet need among patients with BTC. Treatment options are limited, although clinical studies investigating immunotherapy, targeted therapies, and alternative chemotherapy combinations are ongoing. Epidemiological insights may improve patient care and inform the integration of novel therapies for BTC. Keywords: Biliary tract cancer, Intrahepatic cholangiocarcinoma, Extrahepatic cholangiocarcinoma, Gallbladder cancer, Ampulla of Vater cancer
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Gallbladder cancer is a lethal disease with notable geographical variations worldwide and a predilection towards women. Its main risk factor is prolonged exposure to gallstones, although bacterial ...infections and other inflammatory conditions are also associated. The recurrent cycles of gallbladder epithelium damage and repair enable a chronic inflammatory environment that promotes progressive morphological impairment through a metaplasia–dysplasia–carcinoma, along with cumulative genome instability. Inactivation of TP53, which is mutated in over 50% of GBC cases, seems to be the earliest and one of the most important carcinogenic pathways involved. Increased cell turnover and oxidative stress promote early alteration of TP53, cell cycle deregulation, apoptosis and replicative senescence. In this review, we will discuss evidence for the role of inflammation in gallbladder carcinogenesis obtained through epidemiological studies, genome-wide association studies, experimental carcinogenesis, morphogenetic studies and comparative studies with other inflammation-driven malignancies. The evidence strongly supports chronic, unresolved inflammation as the main carcinogenic mechanism of gallbladder cancer, regardless of the initial etiologic trigger. Given this central role of inflammation, evaluation of the potential for GBC prevention removing causes of inflammation or using anti-inflammatory drugs in high-risk populations may be warranted.
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While tobacco and alcohol are established risk factors for hepatocellular carcinoma (HCC), the most common type of primary liver cancer, it is unknown whether they also increase the risk of ...intrahepatic cholangiocarcinoma (ICC). Thus, we examined the association between tobacco and alcohol use by primary liver cancer type.
The Liver Cancer Pooling Project is a consortium of 14 US-based prospective cohort studies that includes data from 1,518,741 individuals (HCC n = 1423, ICC n = 410). Multivariable-adjusted hazards ratios (HRs) and 95% confidence intervals (CI) were estimated using proportional hazards regression.
Current smokers at baseline had an increased risk of HCC (hazard ratio (HR) = 1.86, 95% confidence interval (CI): 1.57-2.20) and ICC (HR = 1.47, 95% CI: 1.07-2.02). Among individuals who quit smoking >30 years ago, HCC risk was almost equivalent to never smokers (HR = 1.09, 95% CI: 0.74-1.61). Compared to non-drinkers, heavy alcohol consumption was associated with an 87% increased HCC risk (HR
= 1.87, 95% CI: 1.41-2.47) and a 68% increased ICC risk (HR
= 1.68, 95% CI: 0.99-2.86). However, light-to-moderate alcohol consumption of <3 drinks/day appeared to be inversely associated with HCC risk (HR
= 0.77, 95% CI: 0.67-0.89; HR
= 0.57, 95% CI: 0.44-0.73; HR
= 0.71, 95% CI: 0.58-0.87), but not ICC.
These findings suggest that, in this relatively healthy population, smoking cessation and light-to-moderate drinking may reduce the risk of HCC.
Despite growing recognition of an etiologic role for inflammation in lung carcinogenesis, few prospective epidemiologic studies have comprehensively investigated the association of circulating ...inflammation markers with lung cancer.
We conducted a nested case-control study (n = 526 lung cancer patients and n = 592 control subjects) within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Control subjects were matched to lung cancer case patients on age, sex, follow-up time (median = 2.9 years), randomization year, and smoking (pack-years and time since quitting). Serum levels of 77 inflammation markers were measured using a Luminex bead-based assay. Conditional logistic regression and weighted Cox models were used to estimate odds ratios (ORs) and cumulative risks, respectively.
Of 68 evaluable markers, 11 were statistically significantly associated with lung cancer risk (P trend across marker categories < .05), including acute-phase proteins (C-reactive protein CRP, serum amyloid A SAA), proinflammatory cytokines (soluble tumor necrosis factor receptor 2 sTNFRII), anti-inflammatory cytokines (interleukin 1 receptor antagonist IL-1RA), lymphoid differentiation cytokines (interleukin 7 IL-7), growth factors (transforming growth factor alpha TGF-A), and chemokines (epithelial neutrophil-activating peptide 78 ENA 78/CXCL5, monokine induced by gamma interferon MIG/CXCL9, B cell-attracting chemokine 1 BCA-1/CXCL13, thymus activation regulated chemokine TARC/CCL17, macrophage-derived chemokine MDC/CCL22). Elevated marker levels were associated with increased lung cancer risk, with odds ratios comparing the highest vs the lowest group ranging from 1.47 (IL-7) to 2.27 (CRP). For IL-1RA, elevated levels were associated with decreased lung cancer risk (OR = 0.71; 95% confidence interval = 0.51 to 1.00). Associations did not differ by smoking, lung cancer histology, or latency. A cross-validated inflammation score using four independent markers (CRP, BCA-1/CXCL13, MDC/CCL22, and IL-1RA) provided good separation in 10-year lung cancer cumulative risks among former smokers (quartile Q 1 = 1.1% vs Q4 = 3.1%) and current smokers (Q1 = 2.3% vs Q4 = 7.9%) even after adjustment for smoking.
Some circulating inflammation marker levels are associated with prospective lung cancer risk.
We evaluated incidence patterns of biliary tract cancers (gallbladder, extrahepatic bile duct, ampulla of Vater and not otherwise specified) to provide potential insight into the etiology of these ...cancers. Data were obtained from the population‐based Surveillance, Epidemiology and End Results program. Rates for cases diagnosed during 1992–2009 were calculated by racial/ethnic, gender and age groups. Temporal trends during 1974–2009 and annual percentage changes (APC) during 1992–2009 were estimated. Age‐adjusted rates by site were higher among American Indian/Alaska Natives, Hispanics (white) and Asian/Pacific Islanders (Asian/PI) and lower among whites and blacks. Gallbladder cancer was more common among women in all ethnic groups (female‐to‐male incidence rate ratio IRR ranged from 1.24 to 2.86), but bile duct and ampulla of Vater cancers were more common among men (female‐to‐male IRR 0.57 to 0.82). Gallbladder cancer rates declined among all racial/ethnic and gender groups except blacks (APC −0.4% to −3.9%). In contrast, extrahepatic bile duct cancer rates rose significantly in most female racial/ethnic groups; the APCs among whites were 0.8 among females and 1.3 among males, both significant. Rates for ampulla of Vater cancer decreased among Asian/PI females (APC −2.7%) but remained stable for the other groups. In addition to confirming that biliary tract cancer incidence patterns differ by gender and site and that the gallbladder cancer incidence rates have been declining, our study provides novel evidence that extrahepatic bile duct cancer rates are rising. These observations may help guide future etiologic studies.
What's new?
Cancers of the biliary tract are rare but often fatal, and the risk factors for them are not well known. Analysis of data from the U.S. Surveillance, Epidemiology, and End Results (SEER) program revealed elevated rates of biliary tract cancers among American Indian/Alaska Natives, Hispanics, and Asian/Pacific Islanders compared with blacks and whites. Gallbladder cancer rates declined among most ethnic groups, whereas extrahepatic bile duct cancer rates rose, especially among women. These observations suggest that these cancers may differ in their etiology and provide clues for further research.
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