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Articles by J. A Meyerhardt
Total Records ( 2 ) for J. A Meyerhardt
  J. A Meyerhardt , E. L Giovannucci , S Ogino , G. J Kirkner , A. T Chan , W Willett and C. S. Fuchs
 

Background  Although physically active individuals have a lower risk of developing colorectal cancer, few studies have examined whether exercise benefits colorectal cancer survivors.

Methods  Derived from the Health Professionals Follow-up Study, we studied colorectal cancer–specific and overall mortality in a cohort of 668 men with a history of stage I to stage III colorectal cancer according to predefined physical activity categories after diagnosis. To minimize bias by occult recurrences, we excluded men who died within 6 months of their postdiagnosis physical activity assessment.

Results  In a cohort of men with colorectal cancer and no apparent metastases at diagnosis, 50.4% exercised at least 18 metabolic equivalent task (MET) hours per week. Increased physical activity was significantly associated with improved colorectal cancer–specific mortality (P = .002 for trend) and overall mortality (P < .001 for trend). Men who engaged in more than 27 MET hours per week of physical activity had an adjusted hazard ratio for colorectal cancer–specific mortality of 0.47 (95% confidence interval, 0.24-0.92) compared with men who engaged in 3 or less MET hours per week of physical activity. The apparent benefit of physical activity was seen regardless of age, disease stage, body mass index, diagnosis year, tumor location, and prediagnosis physical activity.

Conclusion  In a large cohort of men with a history of nonmetastatic colorectal cancer, more physical activity was associated with a lower risk of colorectal cancer–specific and overall mortality.

  S Ogino , K Shima , K Nosho , N Irahara , Y Baba , B. M Wolpin , E. L Giovannucci , J. A Meyerhardt and C. S. Fuchs
 

Energy balance and the AKT pathway are important in colorectal cancer development and regulate p27 (cyclin-dependent kinase inhibitor-1B/CDKN1B/KIP1), which plays a role in preventing cell cycle progression. However, little is known on the clinical outcome or prognostic significance of p27 alterations in relation to patient body mass index (BMI). Among 630 colon cancers (stage I-IV) in two prospective cohort studies, we detected p27 alterations (cytoplasmic p27 localization or p27 loss) in 500 tumors (79%) by immunohistochemistry. The remaining 130 (21%) tumors were "p27-nuclear+." Cox proportional hazard models computed hazard ratios (HR) of deaths, adjusted for patient and tumoral characteristics, including p53, p21, cyclin D1, KRAS, BRAF, PIK3CA, cyclooxygenase-2, fatty acid synthase (FASN), β-catenin, microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and long interspersed nucleotide element-1 (LINE-1) hypomethylation. Compared with p27-nuclear+ patients, p27-altered patients experienced low colon cancer–specific [adjusted HR, 0.63; 95% confidence interval (95% CI), 0.42-0.94] and overall mortality (adjusted HR, 0.70; 95% CI, 0.51-0.95), independent of FASN, MSI, CIMP, LINE-1 methylation, and other potential confounders. The effect of p27 alteration on overall mortality significantly differed by BMI (Pinteraction = 0.013); adjusted HR (p27-altered versus p27-nuclear+ tumors) was 0.28 (95% CI, 0.13-0.59) for BMI ≥30 kg/m2, 0.67 (95% CI, 0.40-1.14) for BMI 25 to 29 kg/m2, and 0.91 (95% CI, 0.57-1.46) for BMI <25 kg/m2. Obesity was associated with inferior overall survival among p27-nuclear+ cases (adjusted HR, 3.07; 95% CI, 1.49-6.32; versus nonobese cases), but not among p27-altered cases (adjusted HR, 1.08). In conclusion, p27 alterations in colon cancer are associated with superior prognosis. Adverse prognostic effect of obesity seems limited to patients with nuclear p27 expression, suggesting a host-tumor interaction. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1849–58)

 
 
 
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