Carcinogenesis Advance Access published online on March 28, 2008
Carcinogenesis, doi:10.1093/carcin/bgn082
Modification of the associations between lifestyle, dietary factors and colorectal cancer risk by APC variants
1 Public Health Sciences, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, UK
2 Colon Cancer Genetics Group, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, UK
3 Environmental & Occupational Medicine Department, University of Aberdeen, Liberty Safe Work Research Centre, Aberdeen, AB25 2DP, UK
4 School of Nursing, Midwifery & Social Care, Faculty of Health, Life and Social Sciences, Napier University, Edinburgh, UK
5 South East Scotland Genetic Service, Western General Hospital, Edinburgh
Corresponding authors: Evropi Theodoratou, Public Health Sciences, College of Medicine and Vet Medicine, University of Edinburgh, UK. Phone 0131 650 3036; Fax 0131 650 6909, E-mail: E.Theodoratou{at}sms.ed.ac.uk; Susan M Farrington, Colon Cancer Genetics Group, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, UK. Phone 0131 467 8422; Fax 0131 467 8450; E-mail: Susan.Farrington{at}hgu.mrc.ac.uk
In a large Scottish case-control study we investigated the effects of 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 (SFAs), mono-unsaturated FAs (MUFAs) and trans FAs (tFAs) had a lower risk of CRC (OR (95% CI): 0.53 (0.41, 0.68); 0.84 (0.72, 0.98); 0.72 (0.62, 0.85); 0.85 (0.73, 1.00); 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, 0.02; respectively). Low n3 poly-unsaturated FA (PUFA) 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.
Key Words: APC Asp1822Val • APC Glu1317Gln • colorectal cancer • fatty acids • hormone replacement therapy
Received October 31, 2007; revised March 18, 2008; accepted March 19, 2008.