NF-κB p65 phosphorylated at serine-536 is an independent prognostic factor in Swedish colorectal cancer patients.

INTRODUCTION: The NF-κB transcription factor protein family has diverse cellular and biological functions, and posttranslational modification is important to regulate these functions. An important site of phosphorylation of NF-κB p65 subunit is at serine-536 (phospho-Ser536-p65), and this phosphorylation is involved in regulation of transcriptional activity, nuclear localization, and protein stability. PATIENTS AND METHODS: In this study, we investigated expression of phospho-Ser536-p65 in colorectal cancers and its relationships with clinicopathological factors. The expression of phospho-Ser536-p65 was examined by immunohistochemistry in 203 primary colorectal cancers, 156 normal mucosa specimens, and 18 metastases in the lymph nodes. RESULTS: The expression of phospho-Ser536-p65 increased from normal mucosa to primary tumor (p < 0.0001). Further, the increased expression of phospho-Ser536-p65 in the cytoplasm of the primary tumors correlated with worse survival of the patients independently of gender, age, tumor location, stage, and differentiation (p = 0.04; hazard ratio, 1.89; 95% CI 1.03-3.47). CONCLUSION: The NF-κB p65 subunit phosphorylated at serine-536 is an independent prognostic factor in colorectal cancer patients.

Expression of NF-κB p65 phosphorylated at serine-536 in rectal cancer with or without preoperative radiotherapy.

BACKGROUND: In the present study, we investigated NF-κB p65 phosphorylated at Serine-536 (phosphor-Ser536-p65) in rectal cancer and its relationship to preoperative radiotherapy (RT), clinicopathological variables and biological factors. PATIENTS AND METHODS: Expression of phosphor-Ser536-p65 was examined by using immunohistochemistry in 141 primary rectal cancers, 149 normal mucosa specimens and 48 metastases in the lymph nodes, from rectal cancer patients who participated in a Swedish clinical trial of preoperative RT. RESULTS: The expression of phosphor-Ser536-p65 in the cytoplasm increased from normal mucosa to primary tumour (p<0.0001, for both the group that did and the group that did not received RT). The expression did not further increase from primary tumour to metastasis in either group (p>0.05). Expression of phosphor-Ser536-p65 was positively related to, or tended to be related to, the expression of tumour endothelium marker 1 (TEM1, p=0.02), FXYD-3 (p=0.001), phosphatase of regenerating liver (PRL, p=0.02), p73 (p=0.048) and meningioma associated protein (MAC30, p=0.05) in the group that received RT but there were no such relationships in the group that did not received RT (p>0.05). The expression of phosphor-Ser536-p65 was not related to clinicopathological factors including survival (p>0.05). CONCLUSIONS: The increased expression of phosphor-Ser536-p65 may be involved in rectal cancer development. After RT, phosphor-Ser536-p65 seems to be positively related to the biological factors, which associated with more malignant features of tumours. However, phosphor-Ser536-p65 was not directly related to the response of RT based on recurrence and survival.

Polymorphism in the promoter region of the NFKBIA gene is rare in Swedish and Chinese colorectal cancer patients and controls.

To investigate whether a -708ins/del8 polymorphism in the promoter region of the NFKBIA gene is related to colorectal cancer risk and clinicopathological variables, we genotyped 92 Swedish and 93 Chinese patients as well as 174 Swedish and 159 Chinese healthy controls by polymerase chain reaction-single stranded conformation polymorphism and DNA sequencing. The -708/del8 polymorphism was found in two Swedish patients and eight Swedish controls, but was absent in the Chinese population. However, among the Chinese population we found other mutations in three patients and in one control. In conclusion, the -708ins/del8 polymorphism is too rare to have a major impact on colorectal cancer incidence in the two populations.

Polymorphism in the promoter region of the NFKB1 gene increases the risk of sporadic colorectal cancer in Swedish but not in Chinese populations.

OBJECTIVE: An insertion/deletion polymorphism (-94ins/delATTG) in the promoter region of the NFKB1 gene correlates to an increased risk of ulcerative colitis, a known risk factor for colorectal cancer, but this polymorphism has not been studied in colorectal cancer patients. The purpose of this study was to investigate whether this polymorphism is related to colorectal cancer risk and clinicopathological variables. MATERIAL AND METHODS: Case samples were taken from four groups of Swedish patients: 193 unselected patients, 90 patients with > or =3 affected 1st-degree relatives, 85 patients with 2 affected 1st-degree relatives, and 109 sporadic cancer patients, and one group of 193 unselected Chinese patients. Controls included 439 Swedish and 458 Chinese healthy individuals. Genotypes were determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism. RESULTS: The deletion increased the risk of colorectal cancer among Swedish unselected patients (OR =3.81, 95% CI: 2.17-6.69, p <0.0001 for heterozygote deletion, and OR=4.65, 95% CI: 2.43-8.89, p <0.0001 for homozygote deletion) and sporadic cancer patients (OR =7.73, 95% CI: 3.06-19.57, p <0.0001 for heterozygote deletion, and OR =6.58, 95% CI: 2.35-18.43, p <0.0001 for homozygote deletion) compared to homozygote insertion (wild-type), but not among the other Swedish or Chinese patients (p >0.05). Similar evidence was seen in age-adjusted analyses (p <0.0001). The polymorphism did not correlate to clinicopathological variables (p >0.05). CONCLUSIONS: Deletion of the polymorphism was associated with increased susceptibility to sporadic colorectal cancers in the Swedish population, but not in the Swedish patients with a family history of colorectal cancer or in Chinese patients.