Author Manuscript Published OnlineFirst on May 19, 2015; DOI: 10.1158/1940-6207.CAPR-15-0075 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited.
Comment on Metformin use and lung cancer risk in patients with diabetes. [Cancer Prev Res (Phila). 2015 Feb;8(2):174-9. doi: 10.1158/1940-6207.CAPR-14-0291.]
“Metformin use and lung cancer risk –Letter.”
Michihiro Mutoh1 and Hideki Ishikawa2 1
Epidemiology and Prevention Division, Research Center for Cancer Prevention and
Screening, National Cancer Center, Tokyo, Japan 2
Department of Molecular-Targeting Cancer Prevention, Kyoto Prefectural University
of Medicine, Kyoto, Japan;
Disclosure of Potential Conflicts of Interest No potential conflicts of interest were disclosed
To the Editor: Here, Sakoda et al. reported that there is no affect of metformin, a cancer chemopreventive agent candidate, on overall lung cancer risk, but in subgroup analysis, metformin use showed higher small cell carcinoma risk, although not statistically significant. We are very impressed by this data because we also experienced modifier effects of smoking in our cancer prevention trials. In addition, several human trials demonstrate that there is an inverse association between non-smokers and smokers in the cancer preventive effects using cancer chemopreventive agents, such as
Downloaded from cancerpreventionresearch.aacrjournals.org on June 6, 2015. © 2015 American Association for Cancer Research.
Author Manuscript Published OnlineFirst on May 19, 2015; DOI: 10.1158/1940-6207.CAPR-15-0075 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited.
beta-carotene, and tea polyphenols. Carotene and Retinol Efficacy Trial (CARET) and Alpha-Tocopherol Beta Carotene Cancer Prevention Study (ATBC Study) indicated that lung cancer incidence was increased among smokers who received beta-carotene (1, 2). Tea polyphenol affects gastric cancer risk according to smoking status, although there is a consistent association between smoking and gastric cancer (3). We recently performed two double-blind, randomized studies using aspirin, in which aspirin similarly increased the risk of colorectal adenomas in the smokers. One is the J-FAPP Study II that included 34 subjects with familial adenomatous polyposis, and compared the effects of aspirin enteric-coated tablets (100 mg/day) and a placebo, with an intervention period of 6 to 10 months (4). The other is the J-CAPP Study that included 311 subjects with prior colorectal tumors (adenomas or early-stage adenocarcinomas), using the same aspirin enteric-coated tablets and placebo for 2 years (5). In the J-FAPP Study II, the odds ratio (OR) for a reduction in the diameter of polyps was 0.10 (CI, 0.01-0.98) in non-smokers (never-smokers/ex-smokers) comparing the aspirin group vs the placebo group, and 3.00 (CI, 0.15-59.89) in current smokers. In the J-CAPP Study, the OR for the presence or absence of tumor recurrence was 0.37 (CI, 0.21-0.68) in non-smokers and 3.45 (CI, 1.12-10.64) in current smokers. The mechanism by which smoking influences the effect of aspirin is unknown. Further studies are warranted to determine if consistent results are obtained by smoking status plus use of cancer chemopreventive agents because this issue is very important for clinical use of cancer chemopreventive agents in the future.
Downloaded from cancerpreventionresearch.aacrjournals.org on June 6, 2015. © 2015 American Association for Cancer Research.
Author Manuscript Published OnlineFirst on May 19, 2015; DOI: 10.1158/1940-6207.CAPR-15-0075 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited.
1) Omenn GS, Goodman GE, Thornquist MD, Balmes J, Cullen MR, Glass A, et al. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med 1996;334:1150-5. 2) Albanes D, Heinonen OP, Taylor PR, Virtamo J, Edwards BK, Rautalahti M, et al. Alpha-Tocopherol and beta-carotene supplements and lung cancer incidence in the alpha-tocopherol, beta-carotene cancer prevention study: effects of base-line characteristics and study compliance. J Natl Cancer Inst 1996;88:1560-70. 3) Sasazuki S, Inoue M, Miura T, Iwasaki M, Tsugane S; Japan Public Health Center-based Prospective Study Group. Plasma tea polyphenols and gastric cancer risk: a case-control study nested in a large population-based prospective study in Japan. Cancer Epidemiol Biomarkers Prev 2008;17:343-51. 4) Ishikawa H, Wakabayashi K, Suzuki S, Mutoh M, Hirata K, Nakamura T, et al. Preventive effects of low-dose aspirin on colorectal adenoma growth in patients with familial adenomatous polyposis: Double-blind, randomized clinical study. Cancer Med 2013;2:50-56. 5) Ishikawa H, Mutoh M, Suzuki S, Tokudome S, Saida Y, Abe T, et al. The preventive effects of low-dose enteric-coated aspirin tablets on the development of colorectal tumours in Asian patients: a randomized trial. Gut 2014;63:1755-9.
Downloaded from cancerpreventionresearch.aacrjournals.org on June 6, 2015. © 2015 American Association for Cancer Research.
Author Manuscript Published OnlineFirst on May 19, 2015; DOI: 10.1158/1940-6207.CAPR-15-0075 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited.
Metformin use and lung cancer risk - Letter. Michihiro Mutoh and Hideki Ishikawa Cancer Prev Res Published OnlineFirst May 19, 2015.
Updated version Author Manuscript
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Comment on Metformin use and lung cancer risk in patients with diabetes. [Cancer Prev Res (Phila). 2015 Feb;8(2):174-9. doi: 10.1158/1940-6207.CAPR-14-0291.]
“Metformin use and lung cancer risk –Letter.”
Michihiro Mutoh1 and Hideki Ishikawa2 1
Epidemiology and Prevention Division, Research Center for Cancer Prevention and
Screening, National Cancer Center, Tokyo, Japan 2
Department of Molecular-Targeting Cancer Prevention, Kyoto Prefectural University
of Medicine, Kyoto, Japan;
Disclosure of Potential Conflicts of Interest No potential conflicts of interest were disclosed
To the Editor: Here, Sakoda et al. reported that there is no affect of metformin, a cancer chemopreventive agent candidate, on overall lung cancer risk, but in subgroup analysis, metformin use showed higher small cell carcinoma risk, although not statistically significant. We are very impressed by this data because we also experienced modifier effects of smoking in our cancer prevention trials. In addition, several human trials demonstrate that there is an inverse association between non-smokers and smokers in the cancer preventive effects using cancer chemopreventive agents, such as
Downloaded from cancerpreventionresearch.aacrjournals.org on June 6, 2015. © 2015 American Association for Cancer Research.
Author Manuscript Published OnlineFirst on May 19, 2015; DOI: 10.1158/1940-6207.CAPR-15-0075 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited.
beta-carotene, and tea polyphenols. Carotene and Retinol Efficacy Trial (CARET) and Alpha-Tocopherol Beta Carotene Cancer Prevention Study (ATBC Study) indicated that lung cancer incidence was increased among smokers who received beta-carotene (1, 2). Tea polyphenol affects gastric cancer risk according to smoking status, although there is a consistent association between smoking and gastric cancer (3). We recently performed two double-blind, randomized studies using aspirin, in which aspirin similarly increased the risk of colorectal adenomas in the smokers. One is the J-FAPP Study II that included 34 subjects with familial adenomatous polyposis, and compared the effects of aspirin enteric-coated tablets (100 mg/day) and a placebo, with an intervention period of 6 to 10 months (4). The other is the J-CAPP Study that included 311 subjects with prior colorectal tumors (adenomas or early-stage adenocarcinomas), using the same aspirin enteric-coated tablets and placebo for 2 years (5). In the J-FAPP Study II, the odds ratio (OR) for a reduction in the diameter of polyps was 0.10 (CI, 0.01-0.98) in non-smokers (never-smokers/ex-smokers) comparing the aspirin group vs the placebo group, and 3.00 (CI, 0.15-59.89) in current smokers. In the J-CAPP Study, the OR for the presence or absence of tumor recurrence was 0.37 (CI, 0.21-0.68) in non-smokers and 3.45 (CI, 1.12-10.64) in current smokers. The mechanism by which smoking influences the effect of aspirin is unknown. Further studies are warranted to determine if consistent results are obtained by smoking status plus use of cancer chemopreventive agents because this issue is very important for clinical use of cancer chemopreventive agents in the future.
Downloaded from cancerpreventionresearch.aacrjournals.org on June 6, 2015. © 2015 American Association for Cancer Research.
Author Manuscript Published OnlineFirst on May 19, 2015; DOI: 10.1158/1940-6207.CAPR-15-0075 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited.
1) Omenn GS, Goodman GE, Thornquist MD, Balmes J, Cullen MR, Glass A, et al. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med 1996;334:1150-5. 2) Albanes D, Heinonen OP, Taylor PR, Virtamo J, Edwards BK, Rautalahti M, et al. Alpha-Tocopherol and beta-carotene supplements and lung cancer incidence in the alpha-tocopherol, beta-carotene cancer prevention study: effects of base-line characteristics and study compliance. J Natl Cancer Inst 1996;88:1560-70. 3) Sasazuki S, Inoue M, Miura T, Iwasaki M, Tsugane S; Japan Public Health Center-based Prospective Study Group. Plasma tea polyphenols and gastric cancer risk: a case-control study nested in a large population-based prospective study in Japan. Cancer Epidemiol Biomarkers Prev 2008;17:343-51. 4) Ishikawa H, Wakabayashi K, Suzuki S, Mutoh M, Hirata K, Nakamura T, et al. Preventive effects of low-dose aspirin on colorectal adenoma growth in patients with familial adenomatous polyposis: Double-blind, randomized clinical study. Cancer Med 2013;2:50-56. 5) Ishikawa H, Mutoh M, Suzuki S, Tokudome S, Saida Y, Abe T, et al. The preventive effects of low-dose enteric-coated aspirin tablets on the development of colorectal tumours in Asian patients: a randomized trial. Gut 2014;63:1755-9.
Downloaded from cancerpreventionresearch.aacrjournals.org on June 6, 2015. © 2015 American Association for Cancer Research.
Author Manuscript Published OnlineFirst on May 19, 2015; DOI: 10.1158/1940-6207.CAPR-15-0075 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited.
Metformin use and lung cancer risk - Letter. Michihiro Mutoh and Hideki Ishikawa Cancer Prev Res Published OnlineFirst May 19, 2015.
Updated version Author Manuscript
E-mail alerts Reprints and Subscriptions Permissions
Access the most recent version of this article at: doi:10.1158/1940-6207.CAPR-15-0075 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited.
Sign up to receive free email-alerts related to this article or journal. To order reprints of this article or to subscribe to the journal, contact the AACR Publications Department at [email protected]. To request permission to re-use all or part of this article, contact the AACR Publications Department at [email protected].
Downloaded from cancerpreventionresearch.aacrjournals.org on June 6, 2015. © 2015 American Association for Cancer Research.
