Colorectal cancer: can nutrients modulate NF-kappaB and apoptosis?
OBJECTIVE
NF-kappaB may promote carcinogenesis by altering cell cycle, inflammatory responses and apoptosis-related gene expression, though cell mechanisms relating diet and colorectal cancer (CRC) remain unveiled in humans. This study in patients with CRC aimed to explore potential interactions between the dietary pattern, nutrient intake, expression of NF-kappaB, apoptosis and tumour histological aggressiveness.


METHODS
Usual diet was assessed by diet history; nutrient composition was determined by DIETPLAN software. Histologically classified patient tissue samples (adenoma, adenocarcinoma and normal surrounding mucosa) were obtained via biopsies during colonoscopy (n=16) or surgery (n=8). NF-kappaB expression was determined by immunohistochemistry and apoptosis by TUNEL assay.


RESULTS
NF-kappaB expression and apoptosis were higher in tumours (p<0.01), greater along with histological aggressiveness (p<0.01). Highest intake terciles of animal protein, refined carbohydrates, saturated fat, n-6 fatty acids and alcohol were associated with higher NF-kappaB, apoptosis and histological aggressiveness (p<0.01); the opposite tissue characteristics were associated with highest intake terciles of n-3 fatty acids, fibre, vitamin E, flavonoids, isoflavones, beta-carotene and selenium (p<0.002). Additionally, higher n-6:n-3 fatty acids ratio (median 26:1) was associated with higher NF-kappaB (p<0.006) and apoptosis (p<0.01), and more aggressive histology (p<0.01). Conversely, lower n-6:n-3 fatty acids ratio (median 6:1) was associated with lower NF-kappaB (p<0.002) and apoptosis (p<0.002), and less aggressive histology (p<0.002).


CONCLUSIONS
NF-kappaB expression and apoptosis increased from adenoma to poorly differentiated adenocarcinoma. This degenerative transition, recognized as key in carcinogenesis, appear to have been influenced by a diet promoting a pro-inflammatory milieu that can trigger NF-kappaB.
Ravasco
Paula
P
Unidade de Nutrição e Metabolismo, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Portugal. p.ravasco@fm.ul.pt
Aranha
Márcia M
MM
Borralho
Pedro M
PM
Moreira da Silva
Isabel B
IB
Correia
Luís
L
Fernandes
Afonso
A
Rodrigues
Cecília M P
CM
Camilo
Maria
M
D000230:Adenocarcinoma / Q000178:diet therapy* / Q000378:metabolism*; D000236:Adenoma / Q000178:diet therapy* / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000178:diet therapy* / Q000378:metabolism*; D003430:Cross-Sectional Studies; D004032:Diet / Q000379:methods; D005260:Female; D015870:Gene Expression; D006801:Humans; D020287:In Situ Nick-End Labeling / Q000379:methods; D008019:Life Style; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D009752:Nutritional Status; D011446:Prospective Studies
D015415:Biomarkers; D016328:NF-kappa B