Modification of the associations between lifestyle, dietary factors and colorectal cancer risk by APC variants.
In a large Scottish case-control study, we investigated the effects of adenomatous polyposis coli (APC) Asp1822Val (rs459552) and APC Glu1317Gln substitutions on colorectal cancer (CRC) risk and whether these associations were influenced by lifestyle and dietary factors. We did not observe any associations between the variants and CRC risk in the whole population. Post-menopausal women taking hormone replacement therapy (HRT) and participants who consumed a diet low in total fat, saturated fatty acids, monounsaturated fatty acids (MUFAs) and trans fatty acids had a lower risk of CRC [odds ratio (95% confidence interval): 0.53 (0.41, 0.68); 0.84 (0.72, 0.98); 0.72 (0.62, 0.85); 0.85 (0.73, 1.00) and 0.78 (0.67, 0.92), respectively]. This risk reduction was stronger in those homozygous for the variant APC 1822 allele with significant interaction relationships for HRT, red meat and MUFA intakes (P for interaction case-only design: 0.02, 0.002 and 0.02, respectively). Low n3 polyunsaturated fatty acids intake was associated with an increased CRC risk for the wild-type and heterozygous APC 1822 individuals but with a decreased CRC risk in those homozygous for the variant allele (P for interaction case-only design: 0.09). The interaction relationships with the APC 1317 variant were of the same direction though not significant, possibly due to the low frequency of the variant allele. Our results confirm the findings of three recent case-control studies suggesting a number of possible biological mechanisms. However, further large-scale studies are necessary in order to replicate these findings and confirm the role of these APC gene variants and their interaction with dietary and lifestyle exposures in colorectal carcinogenesis.
Theodoratou
Evropi
E
Public Health Sciences, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, UK. e.theodoratou@sms.ed.ac.uk
Campbell
Harry
H
Tenesa
Albert
A
McNeill
Geraldine
G
Cetnarskyj
Roseanne
R
Barnetson
Rebecca A
RA
Porteous
Mary E
ME
Dunlop
Malcolm G
MG
Farrington
Susan M
SM
D000483:Alleles; D019943:Amino Acid Substitution; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D004041:Dietary Fats / Q000009:adverse effects*; D005260:Female; D017491:Genes, APC / Q000502:physiology*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006720:Homozygote; D020249:Hormone Replacement Therapy; D006801:Humans; D008019:Life Style; D008297:Male; D008875:Middle Aged; D018570:Risk Assessment; D012307:Risk Factors; D012606:Scotland / Q000453:epidemiology
D004041:Dietary Fats