Carcinogenesis Advance Access originally published online on March 28, 2008
Carcinogenesis 2008 29(9):1774-1780; doi:10.1093/carcin/bgn082
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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, Western General Hospital, University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, 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 EH9 2TB, UK
5 Clinical Genetics Department, University of Edinburgh, Edinburgh EH4 2XU, UK
* To whom correspondence should be addressed. Tel: +44 131 650 3036; Fax: +44 131 650 6909; Email: e.theodoratou{at}sms.ed.ac.uk
Correspondence may also be addressed to Susan M.Farrington. Tel: +44 131 467 8422; Fax: +44 131 467 8450; Email: susan.farrington{at}hgu.mrc.ac.uk
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.
Abbreviations: APC, adenomatous polyposis coli; CI, confidence interval; CRC, colorectal cancer; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; FA, fatty acid; HRT, hormone replacement therapy; MUFA, monounsaturated fatty acid; OR, odds ratio; PUFA, polyunsaturated fatty acid; SFA, saturated fatty acid; tFA, trans fatty acid; tMUFA, trans monounsaturated fatty acid
Received October 31, 2007; revised March 18, 2008; accepted March 19, 2008.
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