Although the unadjusted and adjusted estimates for the association between the measures of SES with p53nac were not statistically significant, a weak association was detected among Medicaid recipients. Patients of low SES may experience different exposures (e.g., diet, infections, air quality, and other environmental exposures) that lead to abnormal p53. Patients with Medicaid coverage may be most representative of low SES patients since Medicaid is typically provided only to low income individuals and families. For patients with Medicaid coverage, the odds of having p53nac were 1.28 times greater than for patients without Medicaid. This positive association supports our hypothesis that low SES patients have higher odds of p53 abnormalities. The finding, however, was not statistically significant.
The other potential measures of SES did not support our hypothesis, but this may be due to limitations in obtaining SES information from medical records. Information on employment was available only in the medical records of individuals, and, since a higher proportion of patients considered unemployed were females and older, these patients may have either had an employed spouse or have been retired and receiving retirement benefits. Therefore, unemployment as measured in this study may not have been a reliable indicator of low SES. For private insurance, actual rates of coverage vary substantially across plans, with variations in both employer and employee premium contributions and in cost-sharing amounts (14
). Therefore, having private health insurance coverage may not directly correlate with SES, as patients could be underinsured or unable to pay the cost-sharing for some procedures. Similarly, patients who receive Medicare prior to retirement were likely previously employed, so it is possible that this group was not of low SES prior to the disability and therefore did not experience the same past exposures as did other low SES patients.
In a previous study, breast cancer patients with low SES (deprivation category 10) had 4.63 times the odds of a p53 mutation compared to patients with high SES (deprivation category 1-9), without adjustment for other factors (11
). Low SES breast cancer patients with p53 mutations had poorer survival than other women. After adjustment for potential confounders, these patients had 2.52 times the rate of death than other breast cancer patients. The association found in this study between Medicaid and p53nac
did not have the same magnitude as reported in the breast cancer study (11
). This difference could be due to an inherently weaker relationship between SES and p53nac
among CRC patients compared to breast cancer patients, to imprecision in our estimate due to limited sample size, or to regional differences in SES and/or p53nac
Most of the alterations in the p53 gene are point (missense) mutations, which lead to altered forms of the p53 protein. These mutant forms generally have a longer half-life than native (wild-type, wt) p53 and can be detected by routine IHC. p53 nuclear accumulation (p53nac
) is not necessarily due to p53 gene mutations, it may also be due to formation of complexes between wt-p53 and other nuclear proteins (e.g., the large T antigen), viral proteins (e.g., SV40), or the major heat shock proteins (hsc-70, 72, and 73) (15
). Such complexes could be the basis for the existence of nonfunctional p53 (16
). In our earlier studies (12
), without use of an antigen recovery (AR) procedure (boiling the tissues in microwave), we demonstrated that, for CRCs (n=107), the IHC technique identified 95% of missense point mutations in p53, using a 10% staining cutoff for p53nac
. When this cut-off value was used, <10% of CRCs exhibited p53nac
without a point mutation in the p53 gene (12
). Furthermore, p53nac
was used to assess the prognoses for CRC patients (8
). Since the data presented in current study were generated following the above described conditions, p53nac
is likely to represent underlying p53 gene mutations and suggests a nonfunctional status of p53. Moreover, detection of abnormal p53 by IHC is a simple and cheap technique to use in clinical settings.
Limitations of this pilot study include that there was not sufficient statistical power to detect modest associations between SES and p53nac
. Further, although health insurance information was available from medical records, information on other commonly used measures of SES, such as education and income, was not available. Employment status may not accurately represent a patient’s SES, since information on household income or spouse’s employment was not included in the medical record. Finally, both race and SES have effects on incidence and mortality from CRC (4
), but, due to our small sample size, we were unable to assess an interaction or effect of race on the association between SES and p53nac
Despite these limitations, this study is, to our knowledge, the first to investigate the association between SES and p53 status among CRC patients. The possible association found between low SES and p53nac
in CRC patients was not as strong as was found for breast cancer patients (11
). Future studies should focus on the association between income and education as markers of SES with p53nac
and should investigate possible interaction between race and SES. It may be important to determine what exposures related to SES cause abnormalities in p53. Although a small fraction of low SES patients had a higher proportion of p53nac
, our findings suggest that it is important to identify the factors that cause molecular abnormalities (like p53nac
) in relation to SES factors and to evaluate their role in CRC development and progression. Furthermore, similar studies will aid in understanding the molecular pathobiology of malignancies and in identifying susceptible individuals within high-risk populations.