Physical Activity, Tumor PTGS2 Expression, and Survival in Patients with Colorectal Cancer

Mai Yamauchi, Paul Lochhead, Yu Imamura, Aya Kuchiba, Xiaoyun Liao, Zhi Rong Qian, Reiko Nishihara, Teppei Morikawa, Kaori Shima, Kana Wu, Edward Giovannucci, Jeffrey A Meyerhardt, Charles S Fuchs, Andrew T Chan, Shuji Ogino

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Abstract

BACKGROUND: Higher levels of physical activity are associated with lower colorectal cancer incidence and mortality, perhaps through influencing energy balance, cellular prostaglandin biosynthesis and systemic inflammation. Although evidence suggests interactive effects of energetics, sedentary lifestyle, and tumor CTNNB1 (beta-catenin) or CDKN1B (p27) status on colon cancer prognosis, interactive effects of physical activity and tumor PTGS2 (the official symbol for cyclooxygenase-2) status on clinical outcome remain unknown. METHODS: Utilizing molecular pathological epidemiology database of 605 stage I-III colon and rectal cancers in two prospective cohort studies (the Nurse's Health Study and the Health Professionals Follow-up Study), we examined patient survival according to post-diagnosis physical activity and tumor PTGS2 status (with 382 PTGS2-positive and 223 PTGS2-negative tumors by immunohistochemistry). Cox proportional hazards models were used to calculate colorectal cancer-specific mortality hazard ratio (HR), adjusting for clinical and other tumor variables including microsatellite instability status. RESULTS: Among PTGS2-positive cases, compared with the least active first quartile, the multivariate HRs (95% confidence interval) were 0.30 (0.14-0.62) for the second, 0.38 (0.20-0.71) for the third, and 0.18 (0.08-0.41) for the fourth quartile of physical activity level (Ptrend=0.0002). In contrast, among PTGS2-negative cases, physical activity level was not significantly associated with survival (Ptrend =0.84; Pinteraction=0.024, between physical activity and tumor PTGS2 status). CONCLUSIONS: Post-diagnosis physical activity is associated with better survival among patients with PTGS2-positive tumors, but not among patients with PTGS2-negative tumors. Impact: Immunohistochemical PTGS2 expression in colorectal carcinoma may serve as a predictive biomarker in pathology practice, which may predict stronger benefit from exercise.
Original languageEnglish
Pages (from-to)1142-1152
Number of pages11
JournalCancer Epidemiology, Biomarkers and Prevention
Volume22
Issue number6
Early online date29 Apr 2013
DOIs
Publication statusPublished - Jun 2013

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Cyclooxygenase 2
Colorectal Neoplasms
Exercise
Survival
Neoplasms
Colonic Neoplasms
Sedentary Lifestyle
Microsatellite Instability
Molecular Epidemiology
Mortality
Health
beta Catenin
Rectal Neoplasms
Proportional Hazards Models
Prostaglandins
Cohort Studies
Biomarkers
Immunohistochemistry
Nurses
Databases

Cite this

Yamauchi, M., Lochhead, P., Imamura, Y., Kuchiba, A., Liao, X., Qian, Z. R., ... Ogino, S. (2013). Physical Activity, Tumor PTGS2 Expression, and Survival in Patients with Colorectal Cancer. Cancer Epidemiology, Biomarkers and Prevention, 22(6), 1142-1152. https://doi.org/10.1158/1055-9965.EPI-13-0108

Physical Activity, Tumor PTGS2 Expression, and Survival in Patients with Colorectal Cancer. / Yamauchi, Mai; Lochhead, Paul; Imamura, Yu; Kuchiba, Aya; Liao, Xiaoyun; Qian, Zhi Rong; Nishihara, Reiko; Morikawa, Teppei; Shima, Kaori; Wu, Kana; Giovannucci, Edward; Meyerhardt, Jeffrey A; Fuchs, Charles S; Chan, Andrew T; Ogino, Shuji.

In: Cancer Epidemiology, Biomarkers and Prevention, Vol. 22, No. 6, 06.2013, p. 1142-1152.

Research output: Contribution to journalArticle

Yamauchi, M, Lochhead, P, Imamura, Y, Kuchiba, A, Liao, X, Qian, ZR, Nishihara, R, Morikawa, T, Shima, K, Wu, K, Giovannucci, E, Meyerhardt, JA, Fuchs, CS, Chan, AT & Ogino, S 2013, 'Physical Activity, Tumor PTGS2 Expression, and Survival in Patients with Colorectal Cancer', Cancer Epidemiology, Biomarkers and Prevention, vol. 22, no. 6, pp. 1142-1152. https://doi.org/10.1158/1055-9965.EPI-13-0108
Yamauchi, Mai ; Lochhead, Paul ; Imamura, Yu ; Kuchiba, Aya ; Liao, Xiaoyun ; Qian, Zhi Rong ; Nishihara, Reiko ; Morikawa, Teppei ; Shima, Kaori ; Wu, Kana ; Giovannucci, Edward ; Meyerhardt, Jeffrey A ; Fuchs, Charles S ; Chan, Andrew T ; Ogino, Shuji. / Physical Activity, Tumor PTGS2 Expression, and Survival in Patients with Colorectal Cancer. In: Cancer Epidemiology, Biomarkers and Prevention. 2013 ; Vol. 22, No. 6. pp. 1142-1152.
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abstract = "BACKGROUND: Higher levels of physical activity are associated with lower colorectal cancer incidence and mortality, perhaps through influencing energy balance, cellular prostaglandin biosynthesis and systemic inflammation. Although evidence suggests interactive effects of energetics, sedentary lifestyle, and tumor CTNNB1 (beta-catenin) or CDKN1B (p27) status on colon cancer prognosis, interactive effects of physical activity and tumor PTGS2 (the official symbol for cyclooxygenase-2) status on clinical outcome remain unknown. METHODS: Utilizing molecular pathological epidemiology database of 605 stage I-III colon and rectal cancers in two prospective cohort studies (the Nurse's Health Study and the Health Professionals Follow-up Study), we examined patient survival according to post-diagnosis physical activity and tumor PTGS2 status (with 382 PTGS2-positive and 223 PTGS2-negative tumors by immunohistochemistry). Cox proportional hazards models were used to calculate colorectal cancer-specific mortality hazard ratio (HR), adjusting for clinical and other tumor variables including microsatellite instability status. RESULTS: Among PTGS2-positive cases, compared with the least active first quartile, the multivariate HRs (95{\%} confidence interval) were 0.30 (0.14-0.62) for the second, 0.38 (0.20-0.71) for the third, and 0.18 (0.08-0.41) for the fourth quartile of physical activity level (Ptrend=0.0002). In contrast, among PTGS2-negative cases, physical activity level was not significantly associated with survival (Ptrend =0.84; Pinteraction=0.024, between physical activity and tumor PTGS2 status). CONCLUSIONS: Post-diagnosis physical activity is associated with better survival among patients with PTGS2-positive tumors, but not among patients with PTGS2-negative tumors. Impact: Immunohistochemical PTGS2 expression in colorectal carcinoma may serve as a predictive biomarker in pathology practice, which may predict stronger benefit from exercise.",
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T1 - Physical Activity, Tumor PTGS2 Expression, and Survival in Patients with Colorectal Cancer

AU - Yamauchi, Mai

AU - Lochhead, Paul

AU - Imamura, Yu

AU - Kuchiba, Aya

AU - Liao, Xiaoyun

AU - Qian, Zhi Rong

AU - Nishihara, Reiko

AU - Morikawa, Teppei

AU - Shima, Kaori

AU - Wu, Kana

AU - Giovannucci, Edward

AU - Meyerhardt, Jeffrey A

AU - Fuchs, Charles S

AU - Chan, Andrew T

AU - Ogino, Shuji

PY - 2013/6

Y1 - 2013/6

N2 - BACKGROUND: Higher levels of physical activity are associated with lower colorectal cancer incidence and mortality, perhaps through influencing energy balance, cellular prostaglandin biosynthesis and systemic inflammation. Although evidence suggests interactive effects of energetics, sedentary lifestyle, and tumor CTNNB1 (beta-catenin) or CDKN1B (p27) status on colon cancer prognosis, interactive effects of physical activity and tumor PTGS2 (the official symbol for cyclooxygenase-2) status on clinical outcome remain unknown. METHODS: Utilizing molecular pathological epidemiology database of 605 stage I-III colon and rectal cancers in two prospective cohort studies (the Nurse's Health Study and the Health Professionals Follow-up Study), we examined patient survival according to post-diagnosis physical activity and tumor PTGS2 status (with 382 PTGS2-positive and 223 PTGS2-negative tumors by immunohistochemistry). Cox proportional hazards models were used to calculate colorectal cancer-specific mortality hazard ratio (HR), adjusting for clinical and other tumor variables including microsatellite instability status. RESULTS: Among PTGS2-positive cases, compared with the least active first quartile, the multivariate HRs (95% confidence interval) were 0.30 (0.14-0.62) for the second, 0.38 (0.20-0.71) for the third, and 0.18 (0.08-0.41) for the fourth quartile of physical activity level (Ptrend=0.0002). In contrast, among PTGS2-negative cases, physical activity level was not significantly associated with survival (Ptrend =0.84; Pinteraction=0.024, between physical activity and tumor PTGS2 status). CONCLUSIONS: Post-diagnosis physical activity is associated with better survival among patients with PTGS2-positive tumors, but not among patients with PTGS2-negative tumors. Impact: Immunohistochemical PTGS2 expression in colorectal carcinoma may serve as a predictive biomarker in pathology practice, which may predict stronger benefit from exercise.

AB - BACKGROUND: Higher levels of physical activity are associated with lower colorectal cancer incidence and mortality, perhaps through influencing energy balance, cellular prostaglandin biosynthesis and systemic inflammation. Although evidence suggests interactive effects of energetics, sedentary lifestyle, and tumor CTNNB1 (beta-catenin) or CDKN1B (p27) status on colon cancer prognosis, interactive effects of physical activity and tumor PTGS2 (the official symbol for cyclooxygenase-2) status on clinical outcome remain unknown. METHODS: Utilizing molecular pathological epidemiology database of 605 stage I-III colon and rectal cancers in two prospective cohort studies (the Nurse's Health Study and the Health Professionals Follow-up Study), we examined patient survival according to post-diagnosis physical activity and tumor PTGS2 status (with 382 PTGS2-positive and 223 PTGS2-negative tumors by immunohistochemistry). Cox proportional hazards models were used to calculate colorectal cancer-specific mortality hazard ratio (HR), adjusting for clinical and other tumor variables including microsatellite instability status. RESULTS: Among PTGS2-positive cases, compared with the least active first quartile, the multivariate HRs (95% confidence interval) were 0.30 (0.14-0.62) for the second, 0.38 (0.20-0.71) for the third, and 0.18 (0.08-0.41) for the fourth quartile of physical activity level (Ptrend=0.0002). In contrast, among PTGS2-negative cases, physical activity level was not significantly associated with survival (Ptrend =0.84; Pinteraction=0.024, between physical activity and tumor PTGS2 status). CONCLUSIONS: Post-diagnosis physical activity is associated with better survival among patients with PTGS2-positive tumors, but not among patients with PTGS2-negative tumors. Impact: Immunohistochemical PTGS2 expression in colorectal carcinoma may serve as a predictive biomarker in pathology practice, which may predict stronger benefit from exercise.

U2 - 10.1158/1055-9965.EPI-13-0108

DO - 10.1158/1055-9965.EPI-13-0108

M3 - Article

C2 - 23629521

VL - 22

SP - 1142

EP - 1152

JO - Cancer Epidemiology, Biomarkers and Prevention

JF - Cancer Epidemiology, Biomarkers and Prevention

SN - 1055-9965

IS - 6

ER -