scholarly journals Smoking, Alcohol, and Biliary Tract Cancer Risk: A Pooling Project of 26 Prospective Studies

2019 ◽  
Vol 111 (12) ◽  
pp. 1263-1278 ◽  
Author(s):  
Emma E McGee ◽  
Sarah S Jackson ◽  
Jessica L Petrick ◽  
Alison L Van Dyke ◽  
Hans-Olov Adami ◽  
...  
Keyword(s):  
Bile Duct ◽  
Alcohol Consumption ◽  
Gallbladder Cancer ◽  
Biliary Tract ◽  
Bile Duct Cancer ◽  
Extrahepatic Bile Duct ◽  
Intrahepatic Bile Duct ◽  
Ampulla Of Vater ◽  
Biliary Tract Cancers ◽  
Duct Cancer

Abstract Background Tobacco and alcohol are well-established risk factors for numerous cancers, yet their relationship to biliary tract cancers remains unclear. Methods We pooled data from 26 prospective studies to evaluate associations of cigarette smoking and alcohol consumption with biliary tract cancer risk. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for associations with smoking and alcohol consumption were calculated. Random-effects meta-analysis produced summary estimates. All statistical tests were two-sided. Results Over a period of 38 369 156 person-years of follow-up, 1391 gallbladder, 758 intrahepatic bile duct, 1208 extrahepatic bile duct, and 623 ampulla of Vater cancer cases were identified. Ever, former, and current smoking were associated with increased extrahepatic bile duct and ampulla of Vater cancers risk (eg, current vs never smokers HR = 1.69, 95% CI = 1.34 to 2.13 and 2.22, 95% CI = 1.69 to 2.92, respectively), with dose-response effects for smoking pack-years, duration, and intensity (all Ptrend < .01). Current smoking and smoking intensity were also associated with intrahepatic bile duct cancer (eg, >40 cigarettes per day vs never smokers HR = 2.15, 95 % CI = 1.15 to 4.00; Ptrend = .001). No convincing association was observed between smoking and gallbladder cancer. Alcohol consumption was only associated with intrahepatic bile duct cancer, with increased risk for individuals consuming five or more vs zero drinks per day (HR = 2.35, 95%CI = 1.46 to 3.78; Ptrend = .04). There was evidence of statistical heterogeneity among several cancer sites, particularly between gallbladder cancer and the other biliary tract cancers. Conclusions Smoking appears to increase the risk of developing all biliary tract cancers except gallbladder cancer. Alcohol may increase the risk of intrahepatic bile duct cancer. Findings highlight etiologic heterogeneity across the biliary tract.

scholarly journals Smoking, Alcohol Consumption, and Risks for Biliary Tract Cancer and Intrahepatic Bile Duct Cancer

2019 ◽  
Vol 29 (5) ◽  
pp. 180-186 ◽  
Author(s):  
Takeshi Makiuchi ◽  
Tomotaka Sobue ◽  
Tetsuhisa Kitamura ◽  
Norie Sawada ◽  
Motoki Iwasaki ◽  
...  
Keyword(s):  
Bile Duct ◽  
Alcohol Consumption ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Bile Duct Cancer ◽  
Intrahepatic Bile Duct ◽  
Tract Cancer ◽  
Duct Cancer

A randomized study of gemcitabine/cisplatin versus single-agent gemcitabine in patients with biliary tract cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4579-4579 ◽  
Author(s):  
J. Furuse ◽  
T. Okusaka ◽  
M. Miyazaki ◽  
H. Taniai ◽  
Y. Nimura ◽  
...  
Keyword(s):  
Bile Duct ◽  
Biliary Tract ◽  
Bile Duct Cancer ◽  
Extrahepatic Bile Duct ◽  
Performance Status ◽  
Single Agent ◽  
Intrahepatic Bile Duct ◽  
Extrahepatic Bile Duct Cancer ◽  
Duct Cancer ◽  
Grade 3

4579 Background: Biliary tract cancers (BTC) are not common but increasing in the US and Europe, and more prevalent in South America and Asia including Japan. Gemcitabine (G) and cisplatin (C) are now deemed as key drugs based on the accumulated literature. This is the first study to compare GC combination with G alone in Japan, even though one phase 3 trial (ABC-02) is ongoing in UK. Methods: 84 Japanese pts, aged ≥ 20 years, with histologically or cytologically confirmed advanced BTC, Performance Status 0 - 1, with adequate bone-marrow, hepatic and renal function were randomized. 83 pts received either C 25 mg/m2 plus G 1000 mg/m2 on days 1, and 8 of each 21-day cycle (GC-arm) or G 1000 mg/m2 on days 1, 8 and 15 of each 28-day cycle (G-arm). Treatments were repeated up to a maximum of 16 cycles of GC or 12 of G until disease progression or unacceptable toxicity occurred. Tumor response was evaluated using RECIST criteria by an independent review committee. The primary end-point of the study was 1- year survival rate. Safety, response rate, duration of progression-free survival were also evaluated. Results: A total of 83 pts (19 extrahepatic bile duct cancer, 28 intrahepatic bile duct cancer, 32 gallbladder cancer and 4 ampullary carcinoma) were eligible for the study protocol defined analysis set (Full Analysis Set, FAS); GC-arm n=41 and G-arm n=42. Baseline characteristics were similar between the two arms: median ages were 65.0 vs 66.5, females were 56.1 vs 50.0%. All pts completed at least one cycle of therapy, yielding a total of 247 cycles (median 6) in GC vs 203 (median 4) in G. The overall response rates were 19.5% (95% CI: 8.8, 34.9) vs 11.9 (95% CI: 4.0, 25.6). The results on survival will be determined and presented at the meeting. The most commonly reported grade 3 or 4 toxicities were: neutropenia (56.1 vs 38.1%), thrombocytopenia (39.0 vs 7.1%), leukopenia (29.3 vs 19.0%), hemoglobin decrease (36.6 vs 16.7%) and γ-GTP increase (29.3 vs 35.7%). Grade 3 acute renal failure was reported in 1 pt on GC. Conclusions: The combination therapy of GC would be an effective and well-tolerated chemotherapy regimen for Japanese pts with advanced BTC. [Table: see text]

Multimodal profiling of biliary tract cancers to detect potentially actionable biomarkers and differences in immune signatures between subtypes.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4023-4023
Author(s):  
Kabir Mody ◽  
Nilofer Saba Azad ◽  
Prerna Jain ◽  
Sherif El-Refai ◽  
Rachna T. Shroff ◽  
...  
Keyword(s):  
Bile Duct ◽  
Biliary Tract ◽  
Extrahepatic Bile Duct ◽  
Intrahepatic Bile Duct ◽  
Relative Increase ◽  
Biliary Tract Cancers ◽  
Cancer Subtypes ◽  
Immune Biomarkers ◽  
The Relationship ◽  
Immune Profiling

4023 Background: Biliary tract cancers (BTC) are increasingly subtyped by molecular alterations, but little is known about the relationship between gain-of-function mutations and the RNA transcript expression of immune-related pathways. Methods: A sample of retrospective, clinicogenomic and transcriptomic data from de-identified records of patients with BTC in the Tempus database was selected. We then investigated the relationship between the mutational landscape and immune-related RNA signatures of different anatomic and genomic BTC subtypes. Results: The cohort included 455 samples of intrahepatic bile duct (IH) (n=267), gallbladder (GB) (n=153), and extrahepatic bile duct (EH) (n=35) cancer subtypes. Across all subtypes, we detected alterations in TP53 (43.8%), ARID1A (19.8%), KMT2C (18.2%), BAP1 (14.6%), KRAS (12.7%), TERT (12.0%), IDH1 (11.4%), KMT2D (11.0%), LRP1B (11.0%), and PBRM1 (10.7%), along with FGFR2 fusions (2.6%). Potentially actionable biomarkers ( FGFR2 and NTRK1-3 fusions, IDH1 and BRAFV600E mutations, tumor mutational burden [TMB]>10, HER2 expression, and/or microsatellite instability) were identified in 21.1% of all BTC and 28.6% of IH samples. Mutually exclusive alterations observed between subtypes were TP53 & BAP1, KRAS & BAP1, TP53 & IDH1, KRAS & IDH1, and SMAD4 & BAP1 ( P < 0.001 for all). GB was more inflamed based on RNA signatures and classical immune biomarkers, including PD-L1 and TMB. RNA signature analyses revealed a higher expression of immune-related pathways in GB than IH ( P = 0.001) with no differences in comparison with EH. PD-L1 expression and continuous TMB were elevated in GB versus the other anatomical subtypes. Significant associations were noted between particular genetic mutations and immune profiling features (table). Conclusions: BTC subtypes are diverse in DNA alterations, RNA inflammatory signatures, and immune markers. Notably, potentially actionable biomarkers were identified in a sizable portion of the cohort and varied significantly between subtypes. These results provide guidance for targeted therapy development and support the use of multimodal immune profiling for BTC. For example, GB-specific clinical trials may be considered due to the relative increase in immune-related biomarkers observed in GB and the historically limited success of BTC trials.[Table: see text]

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