Shared ancestral susceptibility to colorectal cancer and other nutrition related diseases

BMC Medical Genetics

Asta Försti⁷  Pavel Vodicka¹  Kari Hemminki⁷  Jenny Chang-Claude⁶  Hermann Brenner⁵  Jan Novotny⁴  Ludmila Vodickova¹  Michael Hoffmeister⁵  Rebecca Hein²  Alessio Naccarati³  Barbara Pardini³  Anja Rudolph⁶  Melanie Bevier⁸  Stefanie Huhn⁸ 

[1] Institute of Biology and Medical Genetics, 1st Faculty of Medicine, Charles University, Prague 2, 12000, Czech Republic;PMV Forschungsgruppe, University of Cologne, Cologne, 50931, Germany;Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, 14200, Czech Republic;Department of Oncology, General Teaching Hospital, Prague 2, 12808, Czech Republic;Division of Clinical Epidemiology and Aging Research, German Cancer Research Center DKFZ, Heidelberg, 69120, Germany;Division of Cancer Epidemiology, German Cancer Research Center DKFZ, Heidelberg 69120, Germany;Center of Primary Health Care Research, Clinical Research Center, Lund University, Malmö, SE-20502, Sweden;Department of Molecular Genetic Epidemiology, German Cancer Research Center DKFZ, Heidelberg 69120, Germany

关键词: Complex diseases;    Nutrition;    Colorectal cancer;   

Others  :  1177787
DOI  :  10.1186/1471-2350-13-94

 received in 2012-02-28, accepted in 2012-09-28,  发布年份 2012

【 摘 要 】

Background

The majority of non-syndromic colorectal cancers (CRCs) can be described as a complex disease. A two-stage case–control study on CRC susceptibility was conducted to assess the influence of the ancestral alleles in the polymorphisms previously associated with nutrition-related complex diseases.

Methods

In stage I, 28 single nucleotide polymorphisms (SNPs) were genotyped in a hospital-based Czech population (1025 CRC cases, 787 controls) using an allele-specific PCR-based genotyping system (KASPar®). In stage II, replication was carried out for the five SNPs with the lowest p values. The replication set consisted of 1798 CRC cases and 1810 controls from a population-based German study (DACHS). Odds ratios (ORs) and 95% confidence intervals (CIs) for associations between genotypes and CRC risk were estimated using logistic regression. To identify signatures of selection, Fay-Wu’s H and Integrated Haplotype Score (iHS) were estimated.

Results

In the Czech population, carriers of the ancestral alleles of AGT rs699 and CYP3A7 rs10211 showed an increased risk of CRC (OR 1.26 and 1.38, respectively; two-sided p≤0.05), whereas carriers of the ancestral allele of ENPP1 rs1044498 had a decreased risk (OR 0.79; p≤0.05). For rs1044498, the strongest association was detected in the Czech male subpopulation (OR 0.61; p=0.0015). The associations were not replicated in the German population. Signatures of selection were found for all three analyzed genes.

Conclusions

Our study showed evidence of association for the ancestral alleles of polymorphisms in AGT and CYP3A7 and for the derived allele of a polymorphism in ENPP1 with an increased risk of CRC in Czechs, but not in Germans. The ancestral alleles of these SNPs have previously been associated with nutrition-related diseases hypertension (AGT and CYP3A7) and insulin resistance (ENPP1). Future studies may shed light on the complex genetic and environmental interactions between different types of nutrition-related diseases.

【 授权许可】

   
2012 Huhn et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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Figure 3.

【 参考文献 】

• [1]Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010, 127(12):2893-2917.
• [2]Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ: Cancer statistics, 2008. CA Cancer J Clin 2008, 58(2):71-96.
• [3]Laland KN, Odling-Smee J, Myles S: How culture shaped the human genome: bringing genetics and the human sciences together. Nat Rev Genet 2010, 11(2):137-148.
• [4]Bernstein CN, Blanchard JF, Kliewer E, Wajda A: Cancer risk in patients with inflammatory bowel disease: a population-based study. Cancer 2001, 91(4):854-862.
• [5]Huxley RR, Ansary-Moghaddam A, Clifton P, Czernichow S, Parr CL, Woodward M: The impact of dietary and lifestyle risk factors on risk of colorectal cancer: a quantitative overview of the epidemiological evidence. Int J Cancer 2009, 125(1):171-180.
• [6]Il'yasova D, Colbert LH, Harris TB, Newman AB, Bauer DC, Satterfield S, Kritchevsky SB: Circulating levels of inflammatory markers and cancer risk in the health aging and body composition cohort. Cancer Epidemiol Biomarkers Prev 2005, 14(10):2413-2418.
• [7]Bellisari A: Evolutionary origins of obesity. Obes Rev 2008, 9(2):165-180.
• [8]Chen R, Corona E, Sikora M, Dudley JT, Morgan AA, Moreno-Estrada A, Nilsen GB, Ruau D, Lincoln SE, Bustamante CD, et al.: Type 2 diabetes risk alleles demonstrate extreme directional differentiation among human populations, compared to other diseases. PLoS Genet 2012, 8(4):e1002621.
• [9]Di Rienzo A, Hudson RR: An evolutionary framework for common diseases: the ancestral-susceptibility model. Trends Genet 2005, 21(11):596-601.
• [10]Hancock AM, Witonsky DB, Ehler E, Alkorta-Aranburu G, Beall C, Gebremedhin A, Sukernik R, Utermann G, Pritchard J, Coop G, et al.: Colloquium paper: human adaptations to diet, subsistence, and ecoregion are due to subtle shifts in allele frequency. Proc Natl Acad Sci USA 2010, 107(Suppl 2):8924-8930.
• [11]Coop G, Pickrell JK, Novembre J, Kudaravalli S, Li J, Absher D, Myers RM, Cavalli-Sforza LL, Feldman MW, Pritchard JK: The role of geography in human adaptation. PLoS Genet 2009, 5(6):e1000500.
• [12]Fay JC, Wu CI: Hitchhiking under positive Darwinian selection. Genetics 2000, 155(3):1405-1413.
• [13]Oleksyk TK, Smith MW, O'Brien SJ: Genome-wide scans for footprints of natural selection. Philos Trans R Soc Lond B Biol Sci 2010, 365(1537):185-205.
• [14]Tajima F: Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics 1989, 123(3):585-595.
• [15]Voight BF, Kudaravalli S, Wen X, Pritchard JK: A map of recent positive selection in the human genome. PLoS Biol 2006, 4(3):e72.
• [16]The National Center for Biotechnology Information. http://www.ncbi.nlm.nih.gov/
• [17]Barrett JC, Fry B, Maller J, Daly MJ: Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005, 21(2):263-265.
• [18]Thompson EE, Kuttab-Boulos H, Witonsky D, Yang L, Roe BA, Di Rienzo A: CYP3A variation and the evolution of salt-sensitivity variants. Am J Hum Genet 2004, 75(6):1059-1069.
• [19]Kathiresan S, Willer CJ, Peloso GM, Demissie S, Musunuru K, Schadt EE, Kaplan L, Bennett D, Li Y, Tanaka T, et al.: Common variants at 30 loci contribute to polygenic dyslipidemia. Nat Genet 2009, 41(1):56-65.
• [20]Willer CJ, Sanna S, Jackson AU, Scuteri A, Bonnycastle LL, Clarke R, Heath SC, Timpson NJ, Najjar SS, Stringham HM, et al.: Newly identified loci that influence lipid concentrations and risk of coronary artery disease. Nat Genet 2008, 40(2):161-169.
• [21]The.Wellcome.Trust CCC: Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 2007, 447(7145):661-678.
• [22]Groop L: From fused toes in mice to human obesity. Nat Genet 2007, 39(6):706-707.
• [23]Bacci S, Ludovico O, Prudente S, Zhang YY, Di Paola R, Mangiacotti D, Rauseo A, Nolan D, Duffy J, Fini G, et al.: The K121Q polymorphism of the ENPP1/PC-1 gene is associated with insulin resistance/atherogenic phenotypes, including earlier onset of type 2 diabetes and myocardial infarction. Diabetes 2005, 54(10):3021-3025.
• [24]Yanagiya T, Tanabe A, Iida A, Saito S, Sekine A, Takahashi A, Tsunoda T, Kamohara S, Nakata Y, Kotani K, et al.: Association of single-nucleotide polymorphisms in MTMR9 gene with obesity. Hum Mol Genet 2007, 16(24):3017-3026.
• [25]Lo JC, Zhao X, Scuteri A, Brockwell S, Sowers MR: The association of genetic polymorphisms in sex hormone biosynthesis and action with insulin sensitivity and diabetes mellitus in women at midlife. Am J Med 2006, 119(9 Suppl 1):S69-S78.
• [26]Benzinou M, Walley A, Lobbens S, Charles MA, Jouret B, Fumeron F, Balkau B, Meyre D, Froguel P: Bardet-Biedl syndrome gene variants are associated with both childhood and adult common obesity in French Caucasians. Diabetes 2006, 55(10):2876-2882.
• [27]Meyre D, Delplanque J, Chevre JC, Lecoeur C, Lobbens S, Gallina S, Durand E, Vatin V, Degraeve F, Proenca C, et al.: Genome-wide association study for early-onset and morbid adult obesity identifies three new risk loci in European populations. Nat Genet 2009, 41(2):157-159.
• [28]Altshuler DM, Gibbs RA, Peltonen L, Dermitzakis E, Schaffner SF, Yu F, Bonnen PE, de Bakker PI, Deloukas P, The.International.HapMap3.Consortium, et al.: Integrating common and rare genetic variation in diverse human populations. Nature 2010, 467(7311):52-58.
• [29]The.International.HapMap.Consortium: The International HapMap Project. Nature 2003, 426(6968):789-796.
• [30]de Bakker PI, Yelensky R, Pe'er I, Gabriel SB, Daly MJ, Altshuler D: Efficiency and power in genetic association studies. Nat Genet 2005, 37(11):1217-1223.
• [31]Ramensky V, Bork P, Sunyaev S: Human non-synonymous SNPs: server and survey. Nucleic Acids Res 2002, 30(17):3894-3900.
• [32]Pechlivanis S, Bermejo JL, Pardini B, Naccarati A, Vodickova L, Novotny J, Hemminki K, Vodicka P, Forsti A: Genetic variation in adipokine genes and risk of colorectal cancer. Eur J Endocrinol 2009, 160(6):933-940.
• [33]Brenner H, Chang-Claude J, Seiler CM, Rickert A, Hoffmeister M: Protection from colorectal cancer after colonoscopy: a population-based, case-control study. Ann Intern Med 2011, 154(1):22-30.
• [34]Sainz J, Rudolph A, Hein R, Hoffmeister M, Buch S, von Schonfels W, Hampe J, Schafmayer C, Volzke H, Frank B, et al.: Association of genetic polymorphisms in ESR2, HSD17B1, ABCB1, and SHBG genes with colorectal cancer risk. Endocr Relat Cancer 2011, 18(2):265-276.
• [35]Emigh TH: A Comparison of Tests for Hardy-Weinberg Equilibrium. Biometrics 1980, 36(4):627-642.
• [36]Cornfield J: A Method of Estimating Comparative Rates from Clinical Data - Applications to Cancer of the Lung, Breast, and Cervix. J Natl Cancer I 1951, 11(6):1269-1275.
• [37]Southam L, Soranzo N, Montgomery SB, Frayling TM, McCarthy MI, Barroso I, Zeggini E: Is the thrifty genotype hypothesis supported by evidence based on confirmed type 2 diabetes- and obesity-susceptibility variants? Diabetologia 2009, 52(9):1846-1851.
• [38]Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, et al.: The consensus coding sequences of human breast and colorectal cancers. Science 2006, 314(5797):268-274.
• [39]Wood LD, Parsons DW, Jones S, Lin J, Sjoblom T, Leary RJ, Shen D, Boca SM, Barber T, Ptak J, et al.: The genomic landscapes of human breast and colorectal cancers. Science 2007, 318(5853):1108-1113.
• [40]Yu W, Gwinn M, Clyne M, Yesupriya A, Khoury MJ: A navigator for human genome epidemiology. Nat Genet 2008, 40(2):124-125.
• [41]Inoue I, Nakajima T, Williams CS, Quackenbush J, Puryear R, Powers M, Cheng T, Ludwig EH, Sharma AM, Hata A, et al.: A nucleotide substitution in the promoter of human angiotensinogen is associated with essential hypertension and affects basal transcription in vitro. J Clin Invest 1997, 99(7):1786-1797.
• [42]Nakajima T, Wooding S, Sakagami T, Emi M, Tokunaga K, Tamiya G, Ishigami T, Umemura S, Munkhbat B, Jin F, et al.: Natural selection and population history in the human angiotensinogen gene (AGT): 736 complete AGT sequences in chromosomes from around the world. Am J Hum Genet 2004, 74(5):898-916.
• [43]Nebert DW, Dalton TP: The role of cytochrome P450 enzymes in endogenous signalling pathways and environmental carcinogenesis. Nat Rev Cancer 2006, 6(12):947-960.
• [44]McAteer JB, Prudente S, Bacci S, Lyon HN, Hirschhorn JN, Trischitta V, Florez JC: The ENPP1 K121Q polymorphism is associated with type 2 diabetes in European populations: evidence from an updated meta-analysis in 42,042 subjects. Diabetes 2008, 57(4):1125-1130.
• [45]Müssig K, Heni M, Thamer C, Kantartzis K, Machicao F, Stefan N, Fritsche A, Haring HU, Staiger H: The ENPP1 K121Q polymorphism determines individual susceptibility to the insulin-sensitising effect of lifestyle intervention. Diabetologia 2010, 53(3):504-509.
• [46]Lao O, Lu TT, Nothnagel M, Junge O, Freitag-Wolf S, Caliebe A, Balascakova M, Bertranpetit J, Bindoff LA, Comas D, et al.: Correlation between genetic and geographic structure in Europe. Curr Biol 2008, 18(16):1241-1248.
• [47]Nelis M, Esko T, Magi R, Zimprich F, Zimprich A, Toncheva D, Karachanak S, Piskackova T, Balascak I, Peltonen L, et al.: Genetic structure of Europeans: a view from the North-East. PLoS One 2009, 4(5):e5472.
• [48]Calle EE, Kaaks R: Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer 2004, 4(8):579-591.