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Original Investigation
September 17, 2020

Association of Coffee Intake With Survival in Patients With Advanced or Metastatic Colorectal Cancer

Author Affiliations
  • 1currently a medical student at Mayo Clinic School of Medicine, Rochester, Minnesota
  • 2Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts
  • 3Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, Minnesota
  • 4Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, North Carolina
  • 5Southeast Clinical Oncology Research Consortium, Winston-Salem, North Carolina
  • 6Department of Medicine, Indiana University School of Medicine, Indianapolis
  • 7Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles
  • 8SWOG Group Chair’s Office/Knight Cancer Institute, Oregon Health and Science University, Portland
  • 9Department of Medicine, University of California, San Francisco, School of Medicine
  • 10Yale Cancer Center and Smilow Cancer Hospital, New Haven, Connecticut
  • 11Eshelman School of Pharmacy and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
  • 12Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina
  • 13West Virginia University Cancer Institute, Morgantown
  • 14Weill Cornell Medical College, Cornell University and Memorial Sloan Kettering Cancer Center, New York, New York
JAMA Oncol. 2020;6(11):1713-1721. doi:10.1001/jamaoncol.2020.3938
Key Points

Question  Is increased coffee consumption associated with improved survival in patients with advanced or metastatic colorectal cancer?

Findings  In this cohort study of 1171 patients with advanced or metastatic colorectal cancer, increased coffee consumption at the time of study enrollment was associated with lower risk of disease progression and death. Significant associations were noted for both caffeinated and decaffeinated coffee.

Meaning  Among patients with advanced or metastatic colorectal cancer, this study found increased coffee intake to be associated with lower risk of disease progression and death.

Abstract

Importance  Several compounds found in coffee possess antioxidant, anti-inflammatory, and insulin-sensitizing effects, which may contribute to anticancer activity. Epidemiological studies have identified associations between increased coffee consumption and decreased recurrence and mortality of colorectal cancer. The association between coffee consumption and survival in patients with advanced or metastatic colorectal cancer is unknown.

Objective  To evaluate the association of coffee consumption with disease progression and death in patients with advanced or metastatic colorectal cancer.

Design, Setting, and Participants  This prospective observational cohort study included 1171 patients with previously untreated locally advanced or metastatic colorectal cancer who were enrolled in Cancer and Leukemia Group B (Alliance)/SWOG 80405, a completed phase 3 clinical trial comparing the addition of cetuximab and/or bevacizumab to standard chemotherapy. Patients reported dietary intake using a semiquantitative food frequency questionnaire at the time of enrollment. Data were collected from October 27, 2005, to January 18, 2018, and analyzed from May 1 to August 31, 2018.

Exposures  Consumption of total, decaffeinated, and caffeinated coffee measured in cups per day.

Main Outcomes and Measures  Overall survival (OS) and progression-free survival (PFS).

Results  Among the 1171 patients included in the analysis (694 men [59%]; median age, 59 [interquartile range, 51-67] years). The median follow-up time among living patients was 5.4 years (10th percentile, 1.3 years; IQR, 3.2-6.3 years). A total of 1092 patients (93%) had died or had disease progression. Increased consumption of coffee was associated with decreased risk of cancer progression (hazard ratio [HR] for 1-cup/d increment, 0.95; 95% CI, 0.91-1.00; P = .04 for trend) and death (HR for 1-cup/d increment, 0.93; 95% CI, 0.89-0.98; P = .004 for trend). Participants who consumed 2 to 3 cups of coffee per day had a multivariable HR for OS of 0.82 (95% CI, 0.67-1.00) and for PFS of 0.82 (95% CI, 0.68-0.99), compared with those who did not drink coffee. Participants who consumed at least 4 cups of coffee per day had a multivariable HR for OS of 0.64 (95% CI, 0.46-0.87) and for PFS of 0.78 (95% CI, 0.59-1.05). Significant associations were noted for both caffeinated and decaffeinated coffee.

Conclusions and Relevance  Coffee consumption may be associated with reduced risk of disease progression and death in patients with advanced or metastatic colorectal cancer. Further research is warranted to elucidate underlying biological mechanisms.

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    2 Comments for this article
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    Association of coffee intake with disease progression and death in patients with advanced or metastatic colorectal cancer
    Tomoyuki Kawada, MD | Nippon Medical School
    Mackintosh et al. evaluated the association of coffee intake with disease progression and death in patients with advanced or metastatic colorectal cancer (1). Adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) of coffee intake with 1-cup/day increment for cancer progression and death were 0.95 (0.91-1.00) and 0.93 (0.89-0.98). In addition, adjusted HRs (95% CIs) of coffee intake with 2 to 3 cups per day for overall survival (OS) and progression-free survival (PFS) were 0.82 (0.67-1.00) and 0.82 (0.68-0.99). Furthermore, adjusted HRs (95% CIs) of coffee intake with 4 cups per day for OS and PFS were 0.64 (0.46-0.87) and 0.78 (0.59-1.05). Significant associations were noted regardless of caffeine content, and I have a query about their study.

    Loftfield et al. described an invited commentary (2). They mentioned that coffee intake was a daily and a long-term habit with little measurement error by self-report. Aging, cigarette smoking, and alcohol drinking contribute to the risk of chronic diseases, and coffee intake might also be positively correlated with the risk of cancer and other chronic diseases. Contrary to adverse effect of coffee intake on some cancers, Mackintosh et al. reported a preventive/risk-lowering effect of coffee intake on colorectal cancer in patients with advanced or metastatic colorectal cancer.

    I suppose that patients with colorectal cancer, who intake coffee regularly, might keep relatively good health condition. I also speculate that regular coffee intake might be changed according to their health condition. I recommend the authors conducting time-dependent Cox regression analysis by repeated measures of habits on coffee intake.


    References
    1. Mackintosh C, Yuan C, Ou FS, Zhang S, Niedzwiecki D, Chang IW, O'Neil BH, Mullen BC, Lenz HJ, Blanke CD, Venook AP, Mayer RJ, Fuchs CS, Innocenti F, Nixon AB, Goldberg RM, O'Reilly EM, Meyerhardt JA, Ng K. Association of Coffee Intake With Survival in Patients With Advanced or Metastatic Colorectal Cancer. JAMA Oncol. 2020 Sep 17 doi: 10.1001/jamaoncol.2020.3938
    2. Loftfield E, Gunter MJ, Sinha R. Coffee and Colorectal Cancer: Is Improved Survival a "Perk" of Coffee Drinking? JAMA Oncol. 2020 Sep 17. doi: 10.1001/jamaoncol.2020.3313
    CONFLICT OF INTEREST: None Reported
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    In Japan, drinking coffee reduces the risk of colon cancer in women
    takuma hayashi, MBBS, D.M.Sci., GMRC, PhD | National Hospital Organization Kyoto Medical Center
    In recent years, the incidence of colorectal cancer has increased rapidly in Japan. In 2018, Japan's Ministry of Health, Labor and Welfare reported that among all cancer types, colorectal cancer deaths ranked third for men and first for women. Coffee, which is consumed worldwide, has been reported to have a preventive effect on the pathological conditions associated with the development of colorectal cancer by suppressing bile acids in the intestine, which has a carcinogenic promoting effect.
    The relationship between coffee drinking and colorectal cancer is drawing attention. However, the results of a meta-analysis summarizing the research results of coffee drinking
    and colorectal cancer are inconsistent.

    Coffee drinking is associated with a reduced risk of colon cancer in women
    In 2019, the Japan Society of Cancer analyzed the association between drinking coffee and cancers in each part of the large intestine (colon cancer, rectum cancer, proximal colon cancer, distal colon cancer) (1). As a result, in the men, no clear association was found between the development of cancer in each part of the large intestine and drinking coffee. In the women, by analyzing cancer in each part of the large intestine, a 20% lower risk of colon cancer was observed in the group who drank three or more cups of coffee a day compared to the group who drank less than one cup of coffee a day.

    This study found no association between coffee drinking and overall colorectal cancer risk for both men and women. However, analysis of cancer in each part of the large intestine revealed that drinking coffee in women reduced the risk of developing colon cancer. As a mechanism for preventing colon cancer by drinking coffee, it is considered that drinking coffee suppresses intestinal bile acids, which have a carcinogenic promoting effect, inflammation related to colorectal cancer risk, insulin resistance, and insulin secretion. As another mechanism, it is considered that drinking coffee activates the movement of the large intestine.

    Disclosure of potential conflicts of interest
    The authors declare no potential conflicts of interest.

    Acknowledgments
    We thank all the medical staffs and co-medical staffs for providing and helping medical research at National Hospital Organization Kyoto Medical Center.

    Reference
    1. https://epi.ncc.go.jp/en/can_prev/evaluation/index.html
    CONFLICT OF INTEREST: None Reported
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