Obesity is associated with biliary tract cancer mortality and incidence: A pooled analysis of 21 cohort studies in the Asia Cohort Consortium

Isao Oze; Hidemi Ito; Yuriko N. Koyanagi; Sarah Krull Abe; Md Shafiur Rahman; Md Rashedul Islam; Eiko Saito; Prakash C. Gupta; Norie Sawada; Akiko Tamakoshi; Xiao Ou Shu; Ritsu Sakata; Reza Malekzadeh; Ichiro Tsuji; Jeongseon Kim; Chisato Nagata; San Lin You; Sue K. Park; Jian Min Yuan; Myung Hee Shin; Sun Seog Kweon; Mangesh S. Pednekar; Shoichiro Tsugane; Takashi Kimura; Yu Tang Gao; Hui Cai; Akram Pourshams; Yukai Lu; Seiki Kanemura; Keiko Wada; Yumi Sugawara; Chien Jen Chen; Yu Chen; Aesun Shin; Renwei Wang; Yoon Ok Ahn; Min Ho Shin; Habibul Ahsan; Paolo Boffetta; Kee Seng Chia; You Lin Qiao; Nathaniel Rothman; Wei Zheng; Manami Inoue; Daehee Kang; Keitaro Matsuo

doi:10.1002/ijc.34794

Obesity is associated with biliary tract cancer mortality and incidence: A pooled analysis of 21 cohort studies in the Asia Cohort Consortium

Isao Oze, Hidemi Ito, Yuriko N. Koyanagi, Sarah Krull Abe, Md Shafiur Rahman, Md Rashedul Islam, Eiko Saito, Prakash C. Gupta, Norie Sawada, Akiko Tamakoshi, Xiao Ou Shu, Ritsu Sakata, Reza Malekzadeh, Ichiro Tsuji, Jeongseon Kim, Chisato Nagata, San Lin You, Sue K. Park, Jian Min Yuan, Myung Hee ShinSun Seog Kweon, Mangesh S. Pednekar, Shoichiro Tsugane, Takashi Kimura, Yu Tang Gao, Hui Cai, Akram Pourshams, Yukai Lu, Seiki Kanemura, Keiko Wada, Yumi Sugawara, Chien Jen Chen, Yu Chen, Aesun Shin, Renwei Wang, Yoon Ok Ahn, Min Ho Shin, Habibul Ahsan, Paolo Boffetta, Kee Seng Chia, You Lin Qiao, Nathaniel Rothman, Wei Zheng, Manami Inoue, Daehee Kang, Keitaro Matsuo

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Abstract

Body fatness is considered a probable risk factor for biliary tract cancer (BTC), whereas cholelithiasis is an established factor. Nevertheless, although obesity is an established risk factor for cholelithiasis, previous studies of the association of body mass index (BMI) and BTC did not take the effect of cholelithiasis fully into account. To better understand the effect of BMI on BTC, we conducted a pooled analysis using population-based cohort studies in Asians. In total, 905 530 subjects from 21 cohort studies participating in the Asia Cohort Consortium were included. BMI was categorized into four groups: underweight (<18.5 kg/m²); normal (18.5-22.9 kg/m²); overweight (23-24.9 kg/m²); and obese (25+ kg/m²). The association between BMI and BTC incidence and mortality was assessed using hazard ratios (HR) and 95% confidence intervals (CIs) by Cox regression models with shared frailty. Mediation analysis was used to decompose the association into a direct and an indirect (mediated) effect. Compared to normal BMI, high BMI was associated with BTC mortality (HR 1.19 [CI 1.02-1.38] for males, HR 1.30 [1.14-1.49] for females). Cholelithiasis had significant interaction with BMI on BTC risk. BMI was associated with BTC risk directly and through cholelithiasis in females, whereas the association was unclear in males. When cholelithiasis was present, BMI was not associated with BTC death in either males or females. BMI was associated with BTC death among females without cholelithiasis. This study suggests BMI is associated with BTC mortality in Asians. Cholelithiasis appears to contribute to the association; and moreover, obesity appears to increase BTC risk without cholelithiasis.

Original language	English (US)
Pages (from-to)	1174-1190
Number of pages	17
Journal	International Journal of Cancer
Volume	154
Issue number	7
DOIs	https://doi.org/10.1002/ijc.34794
State	Published - Apr 1 2024

Keywords

Asia Cohort Consortium
biliary tract cancer
body mass index
obesity
pooled analysis

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1002/ijc.34794

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Oze, I., Ito, H., Koyanagi, Y. N., Abe, S. K., Rahman, M. S., Islam, M. R., Saito, E., Gupta, P. C., Sawada, N., Tamakoshi, A., Shu, X. O., Sakata, R., Malekzadeh, R., Tsuji, I., Kim, J., Nagata, C., You, S. L., Park, S. K., Yuan, J. M., ... Matsuo, K. (2024). Obesity is associated with biliary tract cancer mortality and incidence: A pooled analysis of 21 cohort studies in the Asia Cohort Consortium. International Journal of Cancer, 154(7), 1174-1190. https://doi.org/10.1002/ijc.34794

Oze, I, Ito, H, Koyanagi, YN, Abe, SK, Rahman, MS, Islam, MR, Saito, E, Gupta, PC, Sawada, N, Tamakoshi, A, Shu, XO, Sakata, R, Malekzadeh, R, Tsuji, I, Kim, J, Nagata, C, You, SL, Park, SK, Yuan, JM, Shin, MH, Kweon, SS, Pednekar, MS, Tsugane, S, Kimura, T, Gao, YT, Cai, H, Pourshams, A, Lu, Y, Kanemura, S, Wada, K, Sugawara, Y, Chen, CJ, Chen, Y, Shin, A, Wang, R, Ahn, YO, Shin, MH, Ahsan, H, Boffetta, P, Chia, KS, Qiao, YL, Rothman, N, Zheng, W, Inoue, M, Kang, D & Matsuo, K 2024, 'Obesity is associated with biliary tract cancer mortality and incidence: A pooled analysis of 21 cohort studies in the Asia Cohort Consortium', International Journal of Cancer, vol. 154, no. 7, pp. 1174-1190. https://doi.org/10.1002/ijc.34794

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title = "Obesity is associated with biliary tract cancer mortality and incidence: A pooled analysis of 21 cohort studies in the Asia Cohort Consortium",

abstract = "Body fatness is considered a probable risk factor for biliary tract cancer (BTC), whereas cholelithiasis is an established factor. Nevertheless, although obesity is an established risk factor for cholelithiasis, previous studies of the association of body mass index (BMI) and BTC did not take the effect of cholelithiasis fully into account. To better understand the effect of BMI on BTC, we conducted a pooled analysis using population-based cohort studies in Asians. In total, 905 530 subjects from 21 cohort studies participating in the Asia Cohort Consortium were included. BMI was categorized into four groups: underweight (<18.5 kg/m2); normal (18.5-22.9 kg/m2); overweight (23-24.9 kg/m2); and obese (25+ kg/m2). The association between BMI and BTC incidence and mortality was assessed using hazard ratios (HR) and 95% confidence intervals (CIs) by Cox regression models with shared frailty. Mediation analysis was used to decompose the association into a direct and an indirect (mediated) effect. Compared to normal BMI, high BMI was associated with BTC mortality (HR 1.19 [CI 1.02-1.38] for males, HR 1.30 [1.14-1.49] for females). Cholelithiasis had significant interaction with BMI on BTC risk. BMI was associated with BTC risk directly and through cholelithiasis in females, whereas the association was unclear in males. When cholelithiasis was present, BMI was not associated with BTC death in either males or females. BMI was associated with BTC death among females without cholelithiasis. This study suggests BMI is associated with BTC mortality in Asians. Cholelithiasis appears to contribute to the association; and moreover, obesity appears to increase BTC risk without cholelithiasis.",

keywords = "Asia Cohort Consortium, biliary tract cancer, body mass index, obesity, pooled analysis",

author = "Isao Oze and Hidemi Ito and Koyanagi, {Yuriko N.} and Abe, {Sarah Krull} and Rahman, {Md Shafiur} and Islam, {Md Rashedul} and Eiko Saito and Gupta, {Prakash C.} and Norie Sawada and Akiko Tamakoshi and Shu, {Xiao Ou} and Ritsu Sakata and Reza Malekzadeh and Ichiro Tsuji and Jeongseon Kim and Chisato Nagata and You, {San Lin} and Park, {Sue K.} and Yuan, {Jian Min} and Shin, {Myung Hee} and Kweon, {Sun Seog} and Pednekar, {Mangesh S.} and Shoichiro Tsugane and Takashi Kimura and Gao, {Yu Tang} and Hui Cai and Akram Pourshams and Yukai Lu and Seiki Kanemura and Keiko Wada and Yumi Sugawara and Chen, {Chien Jen} and Yu Chen and Aesun Shin and Renwei Wang and Ahn, {Yoon Ok} and Shin, {Min Ho} and Habibul Ahsan and Paolo Boffetta and Chia, {Kee Seng} and Qiao, {You Lin} and Nathaniel Rothman and Wei Zheng and Manami Inoue and Daehee Kang and Keitaro Matsuo",

note = "Publisher Copyright: {\textcopyright} 2023 UICC.",

year = "2024",

month = apr,

day = "1",

doi = "10.1002/ijc.34794",

language = "English (US)",

volume = "154",

pages = "1174--1190",

journal = "International Journal of Cancer",

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TY - JOUR

T1 - Obesity is associated with biliary tract cancer mortality and incidence

T2 - A pooled analysis of 21 cohort studies in the Asia Cohort Consortium

AU - Oze, Isao

AU - Ito, Hidemi

AU - Koyanagi, Yuriko N.

AU - Abe, Sarah Krull

AU - Rahman, Md Shafiur

AU - Islam, Md Rashedul

AU - Saito, Eiko

AU - Gupta, Prakash C.

AU - Sawada, Norie

AU - Tamakoshi, Akiko

AU - Shu, Xiao Ou

AU - Sakata, Ritsu

AU - Malekzadeh, Reza

AU - Tsuji, Ichiro

AU - Kim, Jeongseon

AU - Nagata, Chisato

AU - You, San Lin

AU - Park, Sue K.

AU - Yuan, Jian Min

AU - Shin, Myung Hee

AU - Kweon, Sun Seog

AU - Pednekar, Mangesh S.

AU - Tsugane, Shoichiro

AU - Kimura, Takashi

AU - Gao, Yu Tang

AU - Cai, Hui

AU - Pourshams, Akram

AU - Lu, Yukai

AU - Kanemura, Seiki

AU - Wada, Keiko

AU - Sugawara, Yumi

AU - Chen, Chien Jen

AU - Chen, Yu

AU - Shin, Aesun

AU - Wang, Renwei

AU - Ahn, Yoon Ok

AU - Shin, Min Ho

AU - Ahsan, Habibul

AU - Boffetta, Paolo

AU - Chia, Kee Seng

AU - Qiao, You Lin

AU - Rothman, Nathaniel

AU - Zheng, Wei

AU - Inoue, Manami

AU - Kang, Daehee

AU - Matsuo, Keitaro

PY - 2024/4/1

Y1 - 2024/4/1

N2 - Body fatness is considered a probable risk factor for biliary tract cancer (BTC), whereas cholelithiasis is an established factor. Nevertheless, although obesity is an established risk factor for cholelithiasis, previous studies of the association of body mass index (BMI) and BTC did not take the effect of cholelithiasis fully into account. To better understand the effect of BMI on BTC, we conducted a pooled analysis using population-based cohort studies in Asians. In total, 905 530 subjects from 21 cohort studies participating in the Asia Cohort Consortium were included. BMI was categorized into four groups: underweight (<18.5 kg/m2); normal (18.5-22.9 kg/m2); overweight (23-24.9 kg/m2); and obese (25+ kg/m2). The association between BMI and BTC incidence and mortality was assessed using hazard ratios (HR) and 95% confidence intervals (CIs) by Cox regression models with shared frailty. Mediation analysis was used to decompose the association into a direct and an indirect (mediated) effect. Compared to normal BMI, high BMI was associated with BTC mortality (HR 1.19 [CI 1.02-1.38] for males, HR 1.30 [1.14-1.49] for females). Cholelithiasis had significant interaction with BMI on BTC risk. BMI was associated with BTC risk directly and through cholelithiasis in females, whereas the association was unclear in males. When cholelithiasis was present, BMI was not associated with BTC death in either males or females. BMI was associated with BTC death among females without cholelithiasis. This study suggests BMI is associated with BTC mortality in Asians. Cholelithiasis appears to contribute to the association; and moreover, obesity appears to increase BTC risk without cholelithiasis.

AB - Body fatness is considered a probable risk factor for biliary tract cancer (BTC), whereas cholelithiasis is an established factor. Nevertheless, although obesity is an established risk factor for cholelithiasis, previous studies of the association of body mass index (BMI) and BTC did not take the effect of cholelithiasis fully into account. To better understand the effect of BMI on BTC, we conducted a pooled analysis using population-based cohort studies in Asians. In total, 905 530 subjects from 21 cohort studies participating in the Asia Cohort Consortium were included. BMI was categorized into four groups: underweight (<18.5 kg/m2); normal (18.5-22.9 kg/m2); overweight (23-24.9 kg/m2); and obese (25+ kg/m2). The association between BMI and BTC incidence and mortality was assessed using hazard ratios (HR) and 95% confidence intervals (CIs) by Cox regression models with shared frailty. Mediation analysis was used to decompose the association into a direct and an indirect (mediated) effect. Compared to normal BMI, high BMI was associated with BTC mortality (HR 1.19 [CI 1.02-1.38] for males, HR 1.30 [1.14-1.49] for females). Cholelithiasis had significant interaction with BMI on BTC risk. BMI was associated with BTC risk directly and through cholelithiasis in females, whereas the association was unclear in males. When cholelithiasis was present, BMI was not associated with BTC death in either males or females. BMI was associated with BTC death among females without cholelithiasis. This study suggests BMI is associated with BTC mortality in Asians. Cholelithiasis appears to contribute to the association; and moreover, obesity appears to increase BTC risk without cholelithiasis.

KW - Asia Cohort Consortium

KW - biliary tract cancer

KW - body mass index

KW - obesity

KW - pooled analysis

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SP - 1174

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JO - International Journal of Cancer

JF - International Journal of Cancer

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ER -

Obesity is associated with biliary tract cancer mortality and incidence: A pooled analysis of 21 cohort studies in the Asia Cohort Consortium

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