Effect of Aspirin on Cancer Chemoprevention in Japanese Patients With Type 2 Diabetes: 10-Year Observational Follow-up of a Randomized Controlled Trial
Authors: Okada Sadanori , Morimoto Takeshi , Ogawa Hisao , Sakuma Mio , Matsumoto Chisa , Soejima Hirofumi , Nakayama Masafumi , Doi Naofumi , Jinnouchi Hideaki , Waki Masako , Masuda Izuru , Saito Yoshihiko ,   JPAD Trial Investigators, Miwa Kimiaki , Akahoshi Kazunobu , Misumi Kenji , Araki Haruo , Mitsudo Yutaka , Kondo Norifumi , Ashihara Kenichi , Yumoto Shinya , Horimoto Masashi , Doi Osamu , Doijiri Kenichi , Fukami Ryo , Shimabukuro Michio , Egusa Genshi , Goto Kazuo , Hanaoka Yoichi , Kimura Yoshihiro , Haraguchi Yoshikuni , Haraguchi Osamu , Hasegawa Atsushi , Shioya Yoshiko , Shioya Yosuke , Tanaka Eiitiro , Yamada Kazuhiko , Atsumi Toshiya , Tanazawa Satoshi , Horio Yutaka , Ichihara Seishi , Yasuda Isao , Ikeda Tsuneo , Ikemura Makoto , Imamoto Chieko , Iseri Yoshihisa , Iwai Ken , Okamoto Shinya , Sugiyama Seigo , Kamura Masanori , Kan Hirofumi , Kiyota Mayumi , Kawamura Kyousuke , Ono Takashi , Koga Takeshi , Kinuwaki Etsuo , Naito Hiromichi , Kozuma Kazuo , Kudou Kiyotaka , Morikami Yasuhiro , Yasue Hirofumi , Mizuno Yuji , Fujimoto Hisao , Matsuyama Kozaburo , Fujii Hiromi , Kamijikkoku Syuichi , Kuwahara Tetsuo , Takaoka Kyoji , Machii Kazuo , Maeda Kazutaka , Mahara Keiji , Maki Akira , Manda Naoki , Marutsuka Kousuke , Sameshima Naoki , Gi Toshihiro , Matsunaga Terufumi , Matsuo Syuichi , Okubo Hiroto , Minagawa Fuyuki , Minoda Kotaro , Miyata Junichi , Matsuo Takeshi , Momosaki Sueo , Munakata Tetsuo , Nakamura Tomoki , Nagano Hisatoshi , Goshi Kazuto , Sugimoto Keisuke , Naomi Shojiro , Nasu Toshiaki , Tanaka Hiroyuki , Sonoda Ryuji , Kajiwara Keizo , Odo Takafumi , Ogata Hirofumi , Ogihara Masayuki , Ogura Tateo , Oka Keishiro , Kawashima Eiji , Oshima Eiji , Ozaki Ken , Ozawa Seiji , Shono Hiroyuki , Sakamoto Yasuhiro , Sakurai Nobuko , Wakabayashi Chikashi , Sawada Tomohiro , Shibata Junji , Shimono Hisashi , Iemura Akihiro , Matsutani Akira , Suefuji Hisakazu , Sugiyama Hiromichi , Hokamaki Jun , Komori Kenichi , Kinoshita Yoshimi , Murakami Hironori , Hashiguchi Jun , Hashiguchi Yasuhiro , Sawai Koryo , Hifumi Atuko , Seo Koji , Toihata Masamitsu , Tokube Koji , Ogawa Hiroshi , Tomita Fumishi , Taguchi Madoka , Tsubokura Toshio , Tsuchiya Tatsuaki , Tsuda Kaoru , Tsurusaki Ryuichiro , Obata Kenji , Watanabe Katumi , Hayasida Raisuke , Ishibashi Yutaka , Osamura Yoshiaki , Yamanaka Yoshito , Sonoda Kazuhiro , Iwaoka Taisuke , Yokota Hiromitsu , Yoshinari Motoki , Abe Nanami , Ando Noriaki , Bando Hiroshi , Takami Takeshi , Doi Michiaki , Fujii Yoshihiro , Fukuda Masahiro , Fukuoka Yoshiaki , Hamano Masayoshi , Takaoka Minoru , Hasegawa Hiromi , Yabuta Ikuo , Higami Kenshi , Higami Satomi , Yasuno Akiko , Fujinaga Yuriko , Onishi Yoko , Yoshimura Katsutoshi , Minami Shigetoshi , Nakashima Takao , Horie Hiroaki , Horii Kazuko , Matsumura Norihiko , Ikuno Tetsuo , Katsuyama Yoshiyuki , Uemura Shiro , Kikukawa Masao , Kanauchi Masao , Kuzuya Hideshi , Iwasaki Arata , Koutani Takehiko , Makino Hisaharu , Miki Hiroshi , Misugi Susumu , Naito Masaki , Naito Masatoshi , Nakano Yukitaka , Nakatani Akira , Nakatani Fumihiko , Horii Manabu , Yabuta Matahiro , Seno Ayako , Kawata Hiroyuki , Samejima Kenichi , Onoue Kenji , Kawakami Rika , Nakano Tomoya , Ueda Tomoya , Soeda Tsunenari , Kita Yoko , Inoue Fumitaka , Yamano Shigeru , Iwama Hajime , Sakan Hirokazu , Suzuki Megumi , Kagoshima Tadashi , Nakai Takehito , Hashimoto Toshio , Nishitani Yoshiharu , Kobayashi Yoshiyuki , Hoda Koichi , Fujiki Kengo , Uejima Junko , Morikawa Yoshinobu , Kawano Takahiro , Yamada Hideki , Nishimoto Kazuo , Ohsumi Kyouyuki , Ote Nobushige , Oya Akiko , Nishiura Kimiaki , Masuda Joji , Ban Keiichiro , Kyoda Yusuke , Sawada Izumi , Sawada Yoko , Okada Koichi , Yazaki Akihiro , Hanatani Masakazu , Sutani Toshio , Hiramori Yuko , Tanaka Yuya , Igaki Toshiro , Tomioka Yukio , Shiiki Hideo , Sugihara Kiyotaka , Hayashi Motomu , Sasaki Yasunobu , Matsukura Yasuo , Ueda Michiaki , Ueyama Masakuni , Uyama Hideto , Yamada Hiroharu , Yamaga Kenichi , Nakajima Tamio , Yoshimoto Kazumi , Yoshimura Midori 
Published: June 2018

OBJECTIVE
This study analyzed the efficacy of low-dose aspirin in cancer chemoprevention in patients with diabetes.

RESEARCH DESIGN AND METHODS
This study was a posttrial follow-up of the Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial. Participants in the JPAD trial (2,536 Japanese patients with type 2 diabetes and without preexisting cardiovascular disease) were randomly allocated to receive aspirin (81 or 100 mg daily) or no aspirin. After that trial ended in 2008, we followed up with the participants until 2015, with no attempt to change the previously assigned therapy. The primary end point was total cancer incidence. We investigated the effect of low-dose aspirin on cancer incidence.

RESULTS
During the median follow-up period of 10.7 years, a total of 318 cancers occurred. The cancer incidence was not significantly different between the aspirin and no-aspirin groups (log-rank, P = 0.4; hazard ratio [HR], 0.92; 95% CI, 0.73–1.14; P = 0.4). In subgroup analyses, aspirin did not affect cancer incidence in men, women, or participants aged ≥65 years. However, it decreased cancer incidence in participants aged &lt;65 years (log-rank, P = 0.05; HR, 0.67; 95% CI, 0.44–0.99; P = 0.048). After adjusting for sex, hemoglobin A1c, smoking status, and administration of metformin and statins, aspirin significantly reduced cancer incidence in participants aged &lt;65 years (adjusted HR, 0.66; 95% CI, 0.43–0.99; P = 0.04).

CONCLUSIONS
Low-dose aspirin did not reduce cancer incidence in Japanese patients with type 2 diabetes.