A High Body Mass Index or BMI is an indicator of obesity, which has consistently been linked to colorectal cancer, even before a colorectal cancer (CRC) diagnosis was associated with increased risk of death after diagnosis. This increased risk was, according to results of a large prospective study presented at the Annual Meeting of the American Association for Cancer Research (AACR), being held in San Diego, CA, USA, April 5-9, 2014, also observed when tumors harbored the microsatellite instability (MSI) marker normally associated with better prognosis.
Colorectal cancer is with approximately 1 million cases per year the third most common cancer worldwide. Over the last decades, mant researchers have tried to decipher the underlying genetic causes of the disease, including a better understanding of diagnosis and treatment options.
Microsatellites are considered to be phenotypic markers of prognosis, therapeutic response and help identify patients with mutations in DNA repair genes. A large number of observational studies, retrospective data from randomized clinical trials and meta-analyses have consistently shown that tumors that show microsatellite instabilityor deficient mismatch repair (MMR) are associated with improved survival and reduced recurrence of colorectal cancer rates compared to patients with microsatellite stable or MSS tumors.
Independent risk factor
?Our study, to our knowledge, is the first study with sufficient numbers to investigate how these independent risk factors work together to influence survival after a colorectal cancer diagnosis,? notedPeter T. Campbell, Ph.D., director of the Tumor Repository in theEpidemiology Research Programat the American Cancer Society in Atlanta. ?Colorectal cancer patients with tumors with the MSI-high characteristic have a better prognosis than patients with tumors lacking this feature. How obesity, as defined by a high BMI, influences survival of colorectal cancer patients has not been clearly determined.
?We found that a high pre-diagnosis BMI is associated with increased all-cause and colorectal-cancer specific mortality after diagnosis,? Campbell noted. ?We also found that high BMI overrides the survival advantage conferred on patients by an MSI-high tumor.?Our data provide further evidence that maintaining a healthy body weight throughout life is very important,? Campbell continued. ?They also suggest that pre-diagnosis BMI may be something that clinicians should consider when managing patient care.?
…this study is the first study with sufficient numbers to investigate how these independent risk factors work together to influence survival after a colorectal cancer diagnosis…
BMI is calculated as weight in kilograms (kg) divided by height in meters squared (m2). It is used to define healthy weight, overweight, and obesity. In adults, a BMI of 30 or more kg per m2 is considered obese. Campbell and colleagues identified 6,763 patients with invasive colorectal cancer among participants who enrolled in theColon Cancer Family Registryfrom 1997 to 2008. BMI two years before diagnosis was calculated from self-reports of height and weight. Tumor MSI status was available for 4,987 patients. Median follow-up was 5.3 years.
BMI before diagnosis
The researchers found that higher BMI two years before diagnosis increased risk of all-cause mortality after diagnosis: Every 5 kg per m2 increase in BMI increased risk of all-cause mortality by 10%. Similar associations were seen for patients with MSI-high and MSI-stable/MSI-low tumors: Every 5 kg per m2 increase in BMI increased risk of all-cause mortality by 19% and 8%, respectively.
According to Campbell, similar patterns of association were seen for colorectal cancer-specific mortality: Every 5 kg per m2 increase in BMI increased risk of colorectal-cancer specific mortality by 7%.
?Now that we have seen that obesity attenuates the survival advantage observed for patients with MSI-high tumors, we are looking at how it affects other tumor markers that have relevance for colorectal cancer survival,? said Campbell. ?Ultimately, we would like to investigate associations between obesity and somatic tumor mutations to see if we can figure out how obesity drives cancer.?
The study was funded by the National Institutes of Health (NIH) and National Cancer Institute (NCI). Campbell declares no conflicts of interest.
For more information:
 Kitahara CM, Berndt SI, de Gonz?lez AB, Coleman HG, Schoen RE, Hayes RB, Huang WY. Prospective investigation of body mass index, colorectal adenoma, and colorectal cancer in the prostate, lung, colorectal, and ovarian cancer screening trial. J Clin Oncol. 2013 Jul 1;31(19):2450-9. doi: 10.1200/JCO.2012.48.4691.[Article][PubMed]
 Losso GM, Moraes Rda S, Gentili AC, Messias-Reason IT. Microsatellite instability–MSI markers (BAT26, BAT25, D2S123, D5S346, D17S250) in rectal cancer. Arq Bras Cir Dig. 2012 Oct-Dec;25(4):240-4.[Article][PubMed]