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Keywords:

  • race;
  • comorbidity;
  • body mass index;
  • colon cancer;
  • survival

Abstract

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. Conflict of Interest Disclosures
  8. References

BACKGROUND:

There is a survival disparity between African Americans and Caucasians who have colon cancer. The objectives of the current study were to quantify the impact of comorbidity and body mass index (BMI) on survival and to assess whether these 2 variables account for the decreased survival among African Americans.

METHODS:

Data from patients (n = 496) who underwent surgery for a first primary colon cancer at the University of Alabama at Birmingham Hospital from 1981 to 2002 were analyzed. Hazard ratios (HRs) with 95% confidence intervals (CI) were obtained using Cox proportional hazards models for the association of race, comorbidity, BMI, and covariates with all-cause mortality. The confounding influence of comorbidity and BMI for the increased risk of death associated with African-American race was evaluated, and effect modification by disease stage for the association of comorbidity and BMI with mortality also was assessed.

RESULTS:

African Americans experienced an increased risk of death compared with Caucasians (HR, 1.34; 95% CI, 1.06-1.68). The highest comorbidity burden was associated with an increased risk of all-cause mortality (HR, 1.63; 95% CI, 1.24-2.15). For BMI, being underweight increased the risk of death (HR, 1.54; 95% CI, 0.96-2.45); however, being overweight/obese was protective (HR, 0.77; 95% CI, 0.61-0.97). The effect of comorbidity was observed among those with early stage tumors, whereas the effect of BMI was confined to patients who had advanced tumors.

CONCLUSIONS:

Although comorbidity and BMI had an impact on the survival of patients with colon cancer after surgery, these variables were not contributing factors to the decreased survival observed among African Americans. Cancer 2009. © 2009 American Cancer Society.

In 2008, there were an estimated 108,000 new cases of colon cancer and 50,000 deaths from colorectal cancer (CRC), which ranks this cancer third in terms of incidence and mortality among men and women in the United States.1 The public health impact of colon cancer has declined over the past 25 years, as evidenced by a decreasing incidence and better survival because of early detection and improved treatment.2 Despite these improvements, there continues to be a survival disparity among non-Hispanic African Americans and non-Hispanic Caucasians.3, 4 For nearly all cancers, including colon cancer, the survival rate of African Americans is less than that of Caucasians.1 In fact, the difference in survival between African Americans and Caucasians has increased since the middle 1970s.1 Various reasons have been postulated for the survival disparity between the races. Investigators have suggested that differences between African Americans and Caucasians in access to healthcare, exposure to risk factors (eg, obesity), stage at diagnosis, comorbidity, the physician-patient relationship, socioeconomic status, and tumor characteristics may explain the observed racial difference in survival.5-7 The degree to which these factors operate in determining survival, however, remains unknown.

Comorbidity is defined as the presence of other diseases in conjunction with an index disease (eg, colon cancer) of primary interest.8 Comorbid conditions in patients with cancer have an impact on the timing of cancer detection, treatment, prognosis, and outcome.9 Other investigators have speculated that comorbidity may be responsible in part for the decreased survival observed in African Americans with colon cancer.6 Because comorbid conditions exert their effects at multiple levels along the spectrum of care for the cancer patient, failure to account for comorbidity in cancer studies could result in a confounding bias.10 Thus, it is important to assess whether the increased risk of death among African Americans with colon cancer is caused at least in part by failure to account for comorbid conditions in statistical analyses.

The association between obesity and the risk of developing colon cancer has been the subject of numerous epidemiologic investigations.11 The consensus on this issue is that obesity increases the risk of developing colon cancer, although the evidence is stronger for men than for women.12 Despite the many studies that have focused on obesity and incident colon cancer, few have assessed the impact of body habitus and its correlation with survival after a diagnosis. In addition, to our knowledge, no study to date has investigated the role of body mass index (BMI) in the decreased survival observed among African Americans with colon cancer compared with Caucasians. Differences in body habitus between African Americans and Caucasians may shed light on the issue of survival disparity between the races.

The objective of the current study was to assess the role of comorbidity and body habitus in survival after surgery for a population of patients with colon cancer from a single institution. In addition, we investigated the potential confounding influence of comorbidity and BMI as an explanation for the decreased survival of non-Hispanic African Americans with colon cancer relative to non-Hispanic Caucasians. We also examined the impact of comorbidity and BMI by disease stage to increase our understanding of how these risk factors determine survival according to stage. It is our hope that the results of this study will contribute to a greater understanding of the role of comorbidity and BMI and their association with survival after surgery for colon cancer in general and also will allow insight into the survival disparity typically observed between African Americans and Caucasians with colon cancer.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. Conflict of Interest Disclosures
  8. References

Our study population consisted of patients who underwent surgery for sporadic (nonhereditary/familial) adenocarcinoma of the colon at the University of Alabama at Birmingham (UAB) Hospital from 1981 to 2002. The termination date for the accrual of follow-up information was June 1, 2008. The initial patient population comprised 631 individuals. For patients to be eligible for this study, the diagnosis of first primary sporadic colon cancer had to be the earliest diagnosis of any cancer in the patient (with the exception of nonmelanoma skin cancer). Therefore, patients who previously had been diagnosed with other types of cancer or colon cancer (n = 63) were excluded. Also excluded were patients who had multiple primary tumors (n = 13) and those with unknown tumor grade (n = 3). Because an objective of the study was to assess the effect of comorbidity on survival, and because the impact of comorbidity increases with age, patients aged <40 years (n = 22) were excluded to minimize the probability of including individuals who had a family or genetic history of CRC.13 In addition, by excluding patients who survived for <1 month after undergoing tumor resection (n = 21), those who died of complications after surgery were removed from the study population. Also excluded were patients who originally were from other countries (n = 7). Finally, because BMI was a primary variable of interest in this study, 6 individuals with missing height information were excluded. After the above exclusions were made, the study sample consisted of 496 patients. This study was approved by the UAB Institutional Review Board.

Tumor Characteristics

Tumor-specific characteristics were obtained from pathology reports and were adjudicated by 2 of the authors (C.S. and U.M.). Tumors were classified according to the tumor-lymph node-metastasis (TNM) classification and were staged according to the American Joint Committee on Cancer system as stage I, II, III, or IV.14 Tumor grade was recorded as well differentiated, moderately differentiated, poorly differentiated, or unknown (no tumors were graded undifferentiated); and tumor grade was ascertained by a pathologist (C.S.). Well differentiated and moderately differentiated tumors, as suggested by Compton et al,15 were referred to as “low grade,” and poorly differentiated tumors were referred to as “high grade.” The presence of bowel obstruction at the time of surgery and whether the patient received blood transfusions during surgery also was recorded.

Demographics

Demographic, clinical, and patient data regarding age at the time of surgery, sex, race (self-identified), surgery date, insurance status, comorbidity, height and weight, smoking status, information on therapy, and perioperative variables were obtained from medical records. Age was treated as a continuous variable. Year of surgery was categorized in 4 5-year to 6-year intervals based on the distribution of patients from 1981 through 2002. Smoking information was recorded as current, former, or never smoked. Insurance status was recorded as whether or not the patient had private insurance coverage. Information pertaining to adjuvant chemotherapy was ascertained, and a dichotomized variable for the receipt of any chemotherapeutic regimen was created. For each patient, height and weight information was obtained at the time of surgery. In addition, whether or not the patient experienced weight loss before the diagnosis of colon cancer was recorded. From the height and weight data, BMI was calculated as follows:

  • equation image(1)

and each patient was categorized as underweight (BMI, <18.5 kg/m2), normal weight (BMI, 18.5-24.9 kg/m2), overweight (BMI, 25-29.9 kg/m2), or obese (BMI ≥30 kg/m2) according to World Health Organization and National Institutes of Health recommended guidelines.16, 17

Comorbidity

Comorbidity information was abstracted by the primary author (R.B.H.) from the medical records up to the date of surgery. These data were obtained from sources in the medical records, including physician notes, anesthesia notes, nursing notes, and discharge summaries. Only comorbidities that were present before surgery were included in the comorbidity assessment. The 27-item Adult Comorbidity Evaluation (ACE-27) was used as the instrument of comorbidity assessment in this study, because it was designed to assess the comorbidity burden specifically in patients with cancer.18 With the ACE-27, each study patient was given an overall grade of none, mild, moderate, or severe comorbidity, as detailed by Piccirillo et al.18 Because having a previous cancer was an exclusion criterion for this study, information pertaining to cancer was not used in the calculation of comorbidity burden.

Follow-up data on each patient were obtained from the UAB Tumor Registry. This information was updated by the UAB Tumor Registry every 6 months for each patient by contacting either the patient or a family member. If a patient had died since the last follow-up contact, then the date of death was recorded, although the cause of death was not obtained. Patients who remained alive at the study termination date were right censored at the date of last contact. If a patient was recorded as alive, and if ≥3 years had elapsed since the last contact, then the patient was designated as “lost to follow-up.”

Statistical Analysis

Survival was calculated from the date of surgery until the date of death, the date the study was terminated, or the last date of contact for patients who remained alive. The event of interest was death from any cause. All reported P values were 2-sided, and statistical significance was defined as P<.05.

Chi-square statistics for categorical variables and t tests for continuous variables were used to assess differences in vital status, demographic variables, comorbidity, tumor characteristics, chemotherapy status, and perioperative variables according to race. The Kaplan-Meier method was used to compare the survival experience of African Americans and Caucasians, and statistical significance was determined by using the log-rank test. A Cox proportional hazards model was used to obtain bivariate and adjusted hazard ratios (HR) with 95% confidence intervals (CIs) for the association of risk factors and other covariates with mortality. From the bivariate analyses, each variable that obtained P<.20 was considered a potential confounder for the risk factors of interest in this study (race, comorbidity, BMI) and for the association with all-cause mortality. For the multivariate model, potential confounders that met these criteria were included in a model that contained age, disease stage, race, comorbidity, and BMI. The final model was obtained by the step-wise removal (the variable with the highest P value was removed, and the model was reanalyzed) of covariates that no longer were associated with mortality and, thus, were not confounders. By testing the interaction between each variable with time, the proportional hazards assumption was evaluated and was met for race, comorbidity, and BMI in the multivariate model. In addition, the statistical significance of all 2-way interactions between African-American race, comorbidity, body habitus, and disease stage was assessed. From the multivariate model, the confounding influence of comorbidity and BMI for the association of African-American race with survival was evaluated. Finally, effect modification of comorbidity and BMI was assessed by disease stage.

RESULTS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. Conflict of Interest Disclosures
  8. References

Characteristics of the study population by race are listed in Table 1. The proportion of African Americans (39.2%) and Caucasians (60.8%) represented a natural proportion of all patients with colon cancer who underwent surgery at UAB Hospital. Significantly more African Americans had died at the end of follow-up (74.1% vs 62.7%; P<.01). The median time to death for African Americans was >2 years earlier (49.5 months vs 76.1 months; P = .06) than that for Caucasians. There were more African-American women (62.2% vs 49.8%; P<.01), but the distribution according to sex among Caucasians was uniform. Relative to Caucasians, more African Americans enrolled during the earlier years of the study period (1981-1991: 41.4% vs 30.4%; P = .03). African Americans also were less likely to have private insurance (46.6% vs 81.1%; P<.01) and were more likely to be nonsmokers (66.3% vs 55.8%; P = .04). At the time of surgery, there was no difference in the mean age of African-American and Caucasian study participants.

Table 1. Characteristics of the Study Population
CharacteristicNo. of Patients (%)P
African AmericansCaucasians
  1. SD indicates standard deviation; ACE-27, 27-item Adult Comorbidity Evaluation; BMI, body mass index.

Total193 (39.2)303 (60.8)
Status, dead143 (74.1)190 (62.7)<.01
Median overall survival. mo49.576.1.06
Age at surgery: Mean±SD, y67.2±11.866.6±12.5.60
Sex  <.01
 Men73 (37.8)152 (50.2) 
 Women120 (62.2)151 (49.8) 
Surgery date  .03
 1981-198640 (20.7)36 (11.9) 
 1987-199140 (20.7)56 (18.5) 
 1992-199650 (25.9)83 (27.4) 
 1997-200263 (32.6)128 (42.2) 
Private insurance, yes90 (46.6)244 (81.1)<.01
Smoking status  .04
 Nonsmoker128 (66.3)169 (55.8) 
 Former smoker35 (18.1)82 (27.1) 
 Current smoker30 (15.5)52 (17.2) 
ACE-27 comorbidity  <.01
 None25 (13)73 (24.1) 
 Mild69 (35.8)115 (38) 
 Moderate55 (28.5)73 (24.1) 
 Severe44 (22.8)42 (13.9) 
BMI  <.01
 Underweight16 (8.3)8 (2.6) 
 Normal70 (36.3)129 (42.6) 
 Overweight52 (26.9)116 (38.3) 
 Obese55 (28.5)50 (16.5) 
Disease stage  .08
 I34 (17.6)57 (18.8) 
 II63 (32.6)106 (35) 
 III65 (33.7)72 (23.8) 
 IV31 (16.1)68 (22.4) 
Tumor grade  .02
 High28 (14.5)70 (23.1) 
 Low165 (85.5)233 (76.9) 
Chemotherapy, yes36 (18.7)98 (32.3)<.01
Bowel obstruction, yes60 (31.1)87 (28.7).57
Received blood, yes10 (5.2)15 (5).91
Recent weight loss, yes69 (35.8)91 (30).18

Regarding comorbidity, African Americans were more likely to be in the severe category of comorbidity (22.8% vs 13.9%; P<.01) (Table 1). For BMI, proportionately more African Americans were underweight (8.3% vs 2.6%) and obese (28.5% vs 16.5%; P<.01) compared with Caucasians. There was no difference between the races with regard to disease stage at the time of surgery (P = .08), although African Americans were less likely to have high-grade tumors (14.5% v 23.1%; P = .02). African Americans also were less likely to have received adjuvant chemotherapy (18.7% vs 32.3%; P<.01). There was no difference according to race in patients who presented with bowel obstruction, received blood during surgery, or reported recent weight loss before surgery (Table 1).

The association of risk factors with death in the multivariate model is shown in Table 2. On the basis of the results obtained from the unadjusted association of each risk factor with survival, categories were combined when the HRs were similar. Therefore, strata for comorbidity, BMI, and disease stage were combined. According to results obtained in the multivariate model, African Americans experienced a 34% increased risk of death, which was statistically significant (HR, 1.34; 95% CI, 1.06-1.68). In addition, comparison of the adjusted and crude HRs revealed negative confounding, and the risk of death associated with African-American race became stronger in magnitude and statistically significant after adjustment for other risk factors. For comorbidity, only those with the most severe burden had an increased risk of death. Study participants who had severe comorbidity at the time of surgery had a 63% increased risk of death from any cause (HR, 1.63; 95% CI, 1.24-2.15).

Table 2. Bivariate and Adjusted Associations With Death
VariableHR (95% CI)
UnadjustedAdjusted*
  • HR indicates hazard ratio; CI, confidence interval; Ref, reference group; ACE-27, 27-item Adult Comorbidity Evaluation; BMI, body mass index.

  • *

    HRs were adjusted age and for the variables listed.

Race  
 CaucasianRefRef
 African American1.23 (0.99-1.53)1.34 (1.06-1.68)
ACE-27 comorbidity  
 Not severeRefRef
 Severe1.62 (1.24-2.11)1.63 (1.24-2.15)
BMI  
 Underweight1.81 (1.15-2.83)1.54 (0.96-2.45)
 NormalRefRef
 Overweight/obese0.83 (0.66-1.03)0.77 (0.61-0.97)
Disease stage  
 I-IIRef 
 III1.96 (1.51-2.54)1.95 (1.50-2.54)
 IV7.38 (5.55-9.79)8.96 (6.60-12.18)
Tumor grade  
 LowRefRef
 High1.70 (1.32-2.20)1.55 (1.19-2.03)
 Bowel obstruction1.98 (1.58-2.48)1.51 (1.19-1.91)

In the assessment of body habitus at the time of surgery (Table 2), underweight patients were at increased risk of death (HR, 1.54; 95% CI, 0.96-2.45), and the difference was marginally statistically significant; whereas overweight/obese patients had a decreased risk (HR, 0.77; 95% CI, 0.61-0.97). The likelihood ratio test was performed for the overall effect of BMI with death from any cause. The addition of BMI significantly improved the survival model (χ22 = 20.4; P < .01). Disease stage was highly predictive of death. Compared with patients who had stage I or II (early stage) disease, patients who had stage III disease experienced a nearly 2-fold increased risk of death (HR, 1.95; 95% CI, 1.50-2.45), and patients who had stage IV disease had a nearly 9-fold increase in risk (HR, 8.96; 95% CI, 6.60-12.18). High tumor grade was associated with a 55% increased risk (HR, 1.55; 95% CI, 1.19-2.03), and the presence of bowel obstruction increased the risk of death by 51% (HR, 1.51; 95% CI, 1.19-1.91). In the unadjusted analysis, year of surgery (1981-86 vs 1987-2002: HR, 1.42; 95% CI, 1.09-1.85), lack of private insurance (HR, 1.26; 95% CI, 1.01-1.58), receipt of chemotherapy (HR, 1.72; 95% CI, 1.36-2.16), receipt of blood during surgery (HR, 1.95; 95% CI, 1.25-3.03), and recent weight loss (HR, 1.52; 95% CI, 1.22-1.90) all were associated with mortality. However, none of these covariates remained statistically significant in the multivariate model. Furthermore, no interaction terms were statistically significant.

Table 3 displays the association of African-American race with death in 5 models: 1) the crude association, 2) a model adjusted for stage only, 3) a model adjusted for all risk factors other than comorbidity, 4) a model adjusted for all risk factors other than BMI, and 5) the fully adjusted model. The purpose of this analysis was to evaluate the confounding influence of disease stage, comorbidity, and BMI in the association of African-American race with survival. Comparing the HR obtained for the crude association of African-American race with death and the other HRs listed in Table 3, only stage was a confounder of the race correlation. The possibility of confounding by comorbidity and/or BMI was assessed by comparing the HRs obtained for the fully adjusted models without these variables (see Table 3; third and fourth models) with the fully adjusted model (see Table 3; fifth model). If a substantial shift toward the null for the HR associated with African-American race occurred after adjustment for either of these variables, then the conclusion was that 1 or both of these variables, in fact, did explain some of the excess risk of death associated with African-American race. That is, failure to account for the confounding influence of comorbidity and/or BMI in previous studies explained a portion of the increased risk of death for African Americans. Nevertheless, after adjustment for either comorbidity or BMI, there was no meaningful change in the HR associated with African-American race. The conclusion was that neither comorbidity nor BMI was a confounder of the association of race with death and, thus, that comorbidity and BMI did not explain the increased risk of all-cause mortality observed for African Americans.

Table 3. The Association of African-American Race With All-Cause Mortality
VariableHR (95% CI)
UnadjustedAdjusted for StageFully Adjusted Minus Comorbidity*Fully Adjusted Minus BMI*Fully Adjusted*
  • HR indicates hazard ratio; CI, confidence interval; BMI, body mass index; Ref, reference group.

  • *

    The fully adjusted model was adjusted for age, race, comorbidity, BMI, disease stage, tumor grade, and bowel obstruction.

Race     
 CaucasianRefRefRefRefRef
 African American1.23 (0.99-1.53)1.37 (1.10-1.71)1.36 (1.08-1.71)1.38 (1.10-1.73)1.34 (1.06-1.68)

The assessment of effect modification by disease stage for the association of comorbidity and BMI is shown in Table 4. For comorbidity, comparing the ratio measures obtained for early stages with those obtained for advanced stages illustrated the greater impact of comorbidity for patients who had less advanced disease. In addition, both moderate and severe comorbidity were associated with an increased risk of death for patients who had less advanced tumors. For early stages of disease, moderate comorbidity increased the risk of death by 74% (HR, 1.74; 95% CI, 1.14-2.65); patients who had severe comorbidity had a >2-fold increased risk (HR, 2.22; 95% CI, 1.44-3.43). For patients who had stage III tumors, comorbidity was not associated with survival. For patients who had stage IV colon cancer, there was an increased risk of death associated with moderate and severe comorbidity, although the increase was not statistically significant. For BMI, there was no association with death for patients who had early stage disease. The possibility of detecting a statistically significant association between underweight and death was limited because of small patient numbers. Nonetheless, there was an association for those with stage III tumors. Being underweight was associated with an 87% increased risk of death compared with normal weight individuals (HR, 1.87; 95% CI, 0.95-3.69). The protective effect of being overweight/obese was confined to patients who had distant metastatic disease (stage IV); being overweight/obese decreased the risk of death by 42% compared with patients of normal weight (HR, 0.58; 95% CI, 0.37-0.90).

Table 4. The Association of Comorbidity and Body Mass Index With Death by Disease Stage
VariableHR (95% CI)*
Stages I-IIStage IIIStage IV
  • HR indicates hazard ratio; CI indicates confidence interval; Ref, reference group; ACE-27; 27-item Adult Comorbidity Evaluation; BMI, body mass index.

  • *

    HRs were adjusted for age, race, comorbidity, BMI, tumor grade, and obstruction.

ACE-27 comorbidity   
 None/mildRefRefRef
 Moderate1.74 (1.14-2.65)0.99 (0.85-1.68)1.25 (0.77-2.02)
 Severe2.22 (1.44-3.43)1.16 (0.78-1.74)1.80 (0.87-3.72)
BMI   
 Underweight1.07 (0.50-2.27)1.87 (0.95-3.69)1.28 (0.16-10.04)
 NormalRefRefRef
 Overweight/obese0.92 (0.65-1.30)0.92 (0.59-1.45)0.58 (0.37-0.90)

DISCUSSION

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. Conflict of Interest Disclosures
  8. References

For patients with colon cancer, various reasons have been put forth to explain the increased mortality of African Americans relative to Caucasians. The objectives of this study were to quantify the overall effect of comorbidity and BMI on survival among a population of colon cancer patients, to determine whether the decreased survival among African Americans relative to Caucasians is because of the confounding influence of comorbidity and/or BMI, and to assess effect modification for the impact of comorbidity and BMI by disease stage. In the current study, patients with the highest comorbidity burden had an increased risk of death from any cause. The prognostic impact of comorbidity was confined to those with stage I or II disease. Furthermore, being underweight was associated with an increased risk of death for patients with stage III disease, and being overweight or obese was associated with a decreased risk for those with stage IV disease. Finally, the only confounder for the association of race with death was disease stage. Adjustment for comorbidity and BMI did not explain the increased mortality for African-American patients with colon cancer.

Only the developers of the ACE-27 index have used that index of comorbidity assessment in a population of colon cancer patients.18, 19 In the study by Piccirillo et al,18 increasing comorbidity was associated with decreased overall survival for all patients with digestive system tumors. In the current study, only the patients with severe comorbidity had an increased risk of death, as observed in other populations of cancer patients,20 and there also was an effect modification by tumor stage. With increasing stage, the cancer became the primary determinant of survival. This result is consistent with results reported by Read et al19 for colon, breast, and prostate cancer.

Several investigators have adjusted for comorbidity in studies addressing the survival disparity between African Americans relative to Caucasians with colon cancer or CRC.21, 22 Although those studies demonstrated an increased risk of death for African Americans after adjustment for comorbidity, they did not address the question of whether comorbidity accounted for any of the excess risk. This question was addressed by Mayberry et al4 as part of the National Cancer Institute Black/White Cancer Survival Study. Those authors reported an increased risk of death from colon cancer and from all causes for African Americans relative to Caucasians, although the latter increase was not statistically significant. After adjustment for stage, the increased risk of colon cancer-specific death associated with African-American race decreased by 60%. The addition of comorbidity did not result in a further reduction of the HR associated with African Americans. However, it is unclear how comorbidity was defined in their study.

According to Mayberry et al,4 disease stage is the primary determinant of survival differences by race.5 In our results, however, stage actually was a negative confounder of the association with African-American race. This result can be explained by the finding that, although there were no statistically significant differences in stage at diagnosis between African Americans and Caucasians in our study, considerably more Caucasians (22.3% vs 16.8%) were diagnosed with distant metastatic disease. This could account for the increased magnitude of the association for African-American race that became statistically significant after adjustment for disease stage.

To our knowledge, only 1 other study, that by Gomez et al,3 investigated the confounding influence of comorbidity in an attempt to explain the racial differences in survival for patients with colon cancer. Similar to our current findings, those authors observed that comorbidity did not account for the increased risk of overall or colon cancer-specific mortality observed for African Americans. The comorbidity index that they used was the Charlson Comorbidity Index. Although we used a more comprehensive measure of comorbidity assessment (ACE-27) in the current study, we reached the same conclusions as the previous 2 studies.3, 4 That is, comorbidity did not explain any of the increased risk of mortality for African Americans with colon cancer.

The BMI component of the current study was included to contribute to the few studies in the literature on this subject, to address the limitations of previous studies, and to assess the possible confounding influence of BMI for the association of African-American race with mortality. When viewed in the context of disease stage, the increased risk for underweight patients and the decreased risk for overweight/obese patients are biologically plausible and relate to the notion of frailty. Various criteria can be used to identify the frail elderly, including malnutrition and the presence of significant comorbidity.23 In our study, most patients who were underweight were older (mean age, 75.7 years) and had either moderate or severe comorbidity (66.7%). Being underweight can be considered as a marker of decreased biologic reserve and, thus, decreased capacity to compensate for the physical demands imposed by the cancer. Therefore, being overweight/obese can be advantageous for individuals who have metastatic disease. Perhaps having extra weight (biologic reserve) in this scenario translates into a better capacity to withstand the symptoms associated with a cancer of this advanced stage.

In the context of other reported studies, our findings obtained for BMI are consistent with the increased risk associated with underweight but are at odds with studies that reported an increased risk for obese individuals. Meyerhardt et al24 reported that, among men and women with stage II or III colon cancer who were enrolled in a clinical trial, underweight men experienced an increased risk of overall mortality; whereas, for women, obesity was associated with an increased risk of death. In a part of the National Surgical Adjuvant Breast and Bowel Project, Dignam et al25 reported that, among patients with Dukes B and C colon cancer, underweight patients were at increased risk of noncolon cancer-related deaths and that severely obese patients were at increased risk of death from colon cancer. To our knowledge, the current study is the first that has investigated body habitus in an effort to explain the increased risk of death for African Americans with colon cancer.

The current study has several strengths. Our method of comorbidity assessment, comprehensive medical record review, is superior to other methods of comorbidity assessment, eg, the use of administrative data.26 Another asset of this study is the long follow-up period of the study population. Each study participant had the potential to be followed for a minimum of >5 years from the end of the accrual period to termination of the study.

However, there are limitations of the current study. One (which could be an asset) is the ≥20-year period for entry into the study. In an effort to account for improvements in patient care that occurred during this period, the data were adjusted for year of surgery. Nonetheless, between patients who entered the study in the earlier years and patients who entered in the later years, there may be differences in the probability of survival that were not accounted for sufficiently by adjusting for the year of surgery. Another weakness is that information on cause of death was not available. This information would have been useful in determining the impact of comorbidity and BMI on cancer-specific as well as noncancer causes of death.

The issue of racial disparity in survival among patients with cancer is likely multifactorial and has been attributed to various causes. Although the current study has demonstrated that comorbidity and BMI are associated with all-cause mortality in patients with colon cancer, the results presented herein as well as those from previous investigations suggest that comorbidity and BMI probably do not explain the decreased survival associated with African-American race in an academic medical center setting. There is evidence from Veterans Affairs studies to support the finding that, when access to treatment is equivalent, the racial disparity in survival is greatly reduced.21, 22 Whether the survival difference is diminished because of equal access to the medical system, or similarity of socioeconomic background, or other potential confounders among this population, however, is a matter of speculation.27 Because socioeconomic and sociodemographic variables often are unavailable or are measured inadequately, differences in these and other pathobiologic variables between African Americans and Caucasians may be responsible for observed survival differences by race in colon cancer. Further investigations are needed to gain a greater understanding of this complex issue so that efforts can be directed toward the primary cause of mortality differences by race.

Acknowledgements

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. Conflict of Interest Disclosures
  8. References

We thank Donald L. Hill, PhD, Division of Preventive Medicine, University of Alabama at Birmingham, for his critical review of this article.

Conflict of Interest Disclosures

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. Conflict of Interest Disclosures
  8. References

Supported in part by grants from the National Institutes of Health/National Cancer Institute (NIH/NCI) (grants U54-CA118948 and RO1-CA98932-01) to Dr. U. Manne. Robert B. Hines was supported by an NIH/NCI grant (5-R25-CA47888) as part of the Cancer Prevention and Control Training Program. The work involved in the conception of this article was independent of the funding sources.

References

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. Conflict of Interest Disclosures
  8. References