Genetic variability of functional longevity in five rabbit lines

The objectives of this study were to analyse the differences in the genetic determination of functional longevity in five Spanish lines of rabbits and to check how different systematic factors might affect this genetic determination. Four of the lines were maternal (lines A, V, H and LP), these lines were established selecting base generation animals according to different criteria, but in the subsequent generations all of them were selected for litter size at weaning. The other is the paternal line R, this line was constituted by selecting animals with an outstanding daily growth rate. The trait analysed, length of productive life, was the time in days between the date of the first positive pregnancy test and the date of culling or death of a doe. Four models extended from the Cox proportional hazard model were used to analyse data of each line separately and jointly. The complete model (Model 1) included the fixed effect of year-season (YS) combination, positive palpation order (OPP), that is, reproductive cycle, physiological status of the doe (PS) at service and number of kits born alive (NBA) in each kindling as time-dependent factors. The inbreeding coefficient was fitted as a continuous covariate and the animal’s additive genetic effect was also fitted to the model (Model 1). The other models were identical to Model 1 but excluding OPP (Model 2) or PS (Model 3) or NBA (Model 4), which were explored to assess the consequence on additive variance estimates of not correcting for these animal-dependent factors. Estimated effective heritabilities of longevity were 0.07 ± 0.03, 0.03 ± 0.02, 0.14 ± 0.09, 0.05 ± 0.04, 0.02 ± 0.01 and 0.04 ± 0.01 for lines A, V, H, LP, R and for the merged data set, respectively. Removing the PS from the model led to an increase in the estimated additive genetic variance in all lines (0.17 ± 0.05, 0.05 ± 0.03, 0.29 ± 0.19, 0.29 ± 0.20, 0.07 ± 0.04 and 0.05 ± 0.02 for lines A, V, H, LP, R and the merged data set, respectively). The highest hazard of death and/or culling was observed during the first two parities and decreased as the order of parity progressed. Does non-pregnant-non-lactating had the highest risk of death or culling. The does that had zero kits born alive incurred the highest risk, and this risk decreased as the NBA increased. In conclusion, the consideration of longevity as selection criterion for the studied rabbit lines is not recommended.info:eu-repo/semantics/acceptedVersio

Association of GH gene polymorphism with growth and semen traits in rabbits

[EN] Although growth hormone (GH) gene mutations are described in several species, the studies concerning their variabilities and associations with economic traits in rabbits are scarce, particularly associations with semen traits. A total of 149 rabbit bucks from five populations (V-line=36, Moshtohor line=28, APRI line=42, cross ½A½M=23, and Gabali=20) were used in the present study to identify polymorphism of c.-78 C>T single nucleotide polymorphism (SNP) of GH gene among these populations and to investigate the association of GH gene polymorphism with body weight (BW), daily weight gain (DG) and semen traits. DNA was extracted from blood samples for genotyping of c.-78 C>T SNP of GH gene based on polymerase chain reaction with the restriction fragment length polymorphism (PCR-RFLP) technique. The genetic diversity of SNP C>T of GH gene was assessed in terms of genotypic and allelic frequencies, effective number of alleles (Ne), observed (Ho) and expected (He) heterozygosity, Hardy-Weinberg equilibrium (HWE), reduction in heterozygosity due to inbreeding (FIS) and polymorphism information content (PIC). Three genotypes of TT, CC and TC of PCR product of 231 bp of GH gene were detected and all the populations were in HWE in terms of GH gene. The highest Ne was obtained for the Moshtohor line (1.978), while the lowest allelic numbers were obtained for V-line (1.715) and Gabali breed (1.800). The highest genotype frequency of GH gene was 0.48 in TT genotype of V-line, 0.21 in CC genotype of Moshtohor line, 0.67 and 0.56 in TC genotype of ½A½M and Gabali rabbits (P<0.05). The highest frequency for C allele was recorded by Moshtohor line (0.45) and the lowest frequency by Gabali (0.32). The genetic diversity scores for GH gene were intermediate (Ho=0.551, He=0.471, PIC=0.358). The values of Ho ranged from 0.444 in V-line to 0.667 in ½A½M cross, while the values of He were 0.425 in V-line and 0.508 in Moshtohor line. The values of PIC were moderate and ranged from 0.332 in V-line to 0.375 in M-line. The highest FIS was observed in Moshtohor line (0.042) and the lowest value was observed in ½A½M cross (–0.413). The CT genotype of GH gene showed the highest and significant values for body weights at 4, 8, 10 and 12 wk (542, 1131, 1465 and 1861 g) and daily gains at intervals of 4-6 and 8-10 wk (23.1 and 26.5 g). Additionally, the CT genotype recorded the highest and significant values for volume of ejaculate (1.1 mL), sperm motility (57.6%), live sperm (85.6%), normal sperm (93.1%) and sperm concentration in semen (611×106/mL), along with the lowest and significant values for dead sperms (14.4%) and abnormal sperms (6.9%).The authors are very grateful to the Central Laboratory of the Faculty of Veterinary Medicine, Benha University, Egypt for the help and support in molecular genetic analyses. This work was financially supported by the research project entitled “Genetic improvement of local rabbit breeds by using molecular genetic techniques” from the Scientific Research Fund (SRF), Benha University, Egypt.Khalil, MHE.; Zaghloul, AR.; Iraqi, MM.; El Nagar, AG.; Ramadan, SI. (2021). Association of GH gene polymorphism with growth and semen traits in rabbits. World Rabbit Science. 29(1):31-40. https://doi.org/10.4995/wrs.2021.13001OJS3140291Abdel-Kafy E., Hussein B., Abdel-Ghany S., El-Din A., Badawi Y. 2015. Single nucleotide polymorphisms in growth hormone gene are associated with some performance traits in rabbit. Int. J. Biol. Pharm. Allied Sci., 4: 490-504.Afshari K.P., Javanmard A., Asadzadeh N., Sadeghipanah H., Masomi H., Sabrivand A. 2011. Association between GH encoding gene polymorphism and semen characteristics in Iranian Holstein bulls. Afr. J. Biotechnol., 10: 882-886.Alvariño J. 2000. Reproductive performance of male rabbits. In Proc.: 7th World Rabbit Congress, 4-7 July, Valencia, Spain.Amalianingsih T., Brahmantiyo B. 2014. The variability of growth hormone gene associated with ultrasound imaging of longissimus dorsi muscle and perirenal fat in rabbits. Media Peternakan, 37: 1-7. https://doi.org/10.5398/medpet.2014.37.1.1Amiri S., Jemmali B., Ferchichi M. A., Jeljeli H., Boulbaba R., Ben Gara A. 2018. Assessment of growth hormone gene polymorphism effects on reproductive traits in Holstein dairy cattle in Tunisia. Arch. Anim. Breed., 61: 481-489. https://doi.org/10.5194/aab-61-481-2018Bindu, K., Raveendran, A., Antony, S., Raghunandanan, K. 2011. Association of myostatin gene (MSTN ) polymorphism with economic traits in rabbits. In: Fibre production in South American Camelids and other fibre animals. Springer. https://doi.org/10.3920/978-90-8686-727-1_16Darwish S.F., Tarek S.H., Badr M.R. 2016. Association between genotypes of growth hormone gene and semen quality traits in cow bulls and buffalo bulls. Alex. J. Vet. Sci., 49: 147-152. https://doi.org/10.5455/ajvs.221998El-Aksher, S.H., Sherif, H.S., Khalil, M.H., El-Garhy, H.A.S., Ramadan, S. 2017. Molecular analysis of a new synthetic rabbit line and their parental populations using microsatellite and SNP markers. Gene Rep., 8: 17-23.https://doi.org/10.1016/j.genrep.2017.05.001El-Sabrout K., Aggag S. 2017a. Associations between single nucleotide polymorphisms in multiple candidate genes and body weight in rabbits, Vet. World, 10: 136-139. https://doi.org/10.14202/vetworld.2017.136-139El-Sabrout K., Aggag S. 2017b. The gene expression of weaning age and its effect on productive performance of rabbits. World Rabbit Sci., 25: 1-7. https://doi.org/10.4995/wrs.2017.4777El-Tarabany M.S., El-Bayomi K., Abdelhamid T. 2015. Semen characteristics of purebred and crossbred male rabbits. PloS one, 10: e0128435. https://doi.org/10.1371/journal.pone.0128435Estany J., Baselga M., Blasco A., Camacho J. 1989. Mixed model methodology for the estimation of genetic response to selection in litter size of rabbits. Lives. Prod. Sci., 21: 67-75. https://doi.org/10.1016/0301-6226(89)90021-3Fontanesi L., Tazzoli M., Scotti E., Russo V. 2008. Analysis of candidate genes for meat production traits in domestic rabbit breeds. In Proc.: 9th World Rabbit Congress, 10-13 June 2008,.Verona, Italy.Fontanesi L., Dall'Olio S., Spaccapaniccia E., Scotti E., Fornasini D., Frabetti A.. 2012. A single nucleotide polymorphism in the rabbit growth hormone (GH1) gene is associated with market weight in a commercial rabbit population. Livest. Sci., 147: 84-88. https://doi.org/10.1016/j.livsci.2012.04.006Gencheva D., Georgieva S., Velikov K., Koynarski T., Tanchev S. 2017. Single nucleotide polymorphism of the Growth Hormone Receptor (GHR) encoding gene in Oryctolagus cuniculus. J. BioSci. Biotechnol. 6: 197-201.Gidenne T., Garreau H., Drouilhet L., Aubert C., Maertens L. 2017. Improving feed efficiency in rabbit production, A review on nutritional, technico-economical, genetic and environmental aspects. Anim. Feed Sci. Technol., 225: 109-122. https://doi.org/10.1016/j.anifeedsci.2017.01.016Groeneveld E. 2006. PEST user's manual. Institute of Animal Husbandry and Animal Behaviour, Mariensee, Germany, FAL, Germany.Hristova D., Tanchev S., Velikov K., Gonchev P., Georgieva S. 2017. Rabbit growth hormone and myostatin gene polymorphisms. J. Agric. Res., 2: 000133 (Open Access). https://doi.org/10.23880/OAJAR-16000133Hristova D.G., Tanchev S., Velikov K., Gonchev P., Georgieva S. 2018. Single nucleotide polymorphism of the growth hormone (GH) encoding gene in inbred and outbred domestic rabbits. World Rabbit Sci., 26: 49-55. https://doi.org/10.4995/wrs.2018.7211Iraqi M., Afifi E., Baselga M., Khalil M., García M. 2008. Additive and heterotic components for post-weaning growth traits in a crossing project of V-line with Gabali rabbits in Egypt. In Proc.: 9th World Rabbit Congress, 10-13 June 2008, Verona, Italy.Kalinowski, S.T., Taper, M.L., Marshall, T.C. 2007. Revising how the computer program CERVUS accommodates genotyping error increases success in paternity assignment. Molecular Ecology, 16: 1099-1106. https://doi.org/10.1111/j.1365-294X.2007.03089.xKhalil M., Baselga M. 2002. Rabbit genetic resources in Mediterranean countries. In M. H. Khalil & M. Baselga (Eds.), Options Méditerranéennes (Vol. Série B, pp. 262). Zaragoza, Spain: CIHEAM-IAMZ.Khalil M.H., Al-Sobayil K., Al-Saef A., García M., Baselga M. 2007. Genetic evaluation for semen characteristics in a crossbreeding project involving Saudi and Spanish V-line rabbits. Animal, 1: 923-928. https://doi.org/10.1017/S1751731107000341Kmieć M., Terman A., Wierzbicki H., Zych S. 2007. Association of GH gene polymorphism with semen parameters of boars. Acta Vet. Brno., 76: 41-46. https://doi.org/10.2754/avb200776010041Lavara R., García M., Torres C., Vicente J., Baselga M. 2008. Genetic parameters for semen traits of rabbit males: II. Motility. In Proc.: 9th World Rabbit Congress., 10-13 June 2008, Verona, Italy.Lavara, R., Vicente, J., Baselga, M. 2011. Genetic parameter estimates for semen production traits and growth rate of a paternal rabbit line. J. Anim. Breed. Genet., 128: 44-51. https://doi.org/10.1111/j.1439-0388.2010.00889.xLavara, R., David, I., Moce, E., Baselga, M., Vicente, J. 2013. Environmental and male variation factors of freezability in rabbit semen. Theriogenology, 79: 582-589. https://doi.org/10.1016/j.theriogenology.2012.11.007Maertens L., Gidenne T. 2016. Feed efficiency in rabbit production: nutritional, technico-economical and environmental aspects. In Proc.: 11th World Rabbit Congress, 15-18 June, Qingdao, China.Migdal L., Palka S., Kmiecik M., Derewicka O. 2019. Association of polymorphisms in the GH and GHR genes with growth and carcass traits in rabbits (Oryctolagus cuniculus). Czech J. Anim. Sci., 64: 255-264. https://doi.org/10.17221/27/2019-CJASNikbin S., Panandam J.M., Yaakub H., Murugaiyah M. 2018. Association of novel SNPs in gonadotropin genes with sperm quality traits of Boer goats and Boer crosses. J. Applied Anim. Res., 46: 459-466. https://doi.org/10.1080/09712119.2017.1336441Pal A., Chakravarty A.K., Chatterjee P.N. 2014. Polymorphism of growth hormone gene and its association with seminal and sexual behavioral traits in crossbred cattle. Theriogenology, 81: 474-480. https://doi.org/10.1016/j.theriogenology.2013.11.002Peakall P., Smouse R. 2012. GenAlEx 6.5: Genetic analysis in Excel. Population genetic software for teaching and research. An update. Bioinformatics, 28: 2537-2539. https://doi.org/10.1093/bioinformatics/bts460Raymond M. 1995. GENEPOP (version 1.2): Population Genetics Software for exact tests and ecumenicism. J. Hered., 86: 248-249. https://doi.org/10.1093/oxfordjournals.jhered.a111573Sahwan F.M., El-Sheik A.I., Sharaf M.M., El-Nahas A.F. 2014. Genetic polymorphism in growth hormone receptor gene (GHR) and its relationship with growth trait in pure and hybrid rabbit breeds. Alex. J. Vet. Sci., 43: 45-51. https://doi.org/10.5455/ajvs.165197Tanchev S. 2015. Conservation of genetic resources of autochthonous domestic livestock breeds in Bulgaria. A review. Bulgarian J. Agric. Sci., 21: 1262-1271.Tusell L., Legarra A., García-Tomás M., Rafel O., Ramon J., Piles M. 2012. Genetic basis of semen traits and their relationship with growth rate in rabbits. J. Anim. Sci. 90: 1385-1397. https://doi.org/10.2527/jas.2011-4165Yardibi H., Hosturk G.T., Paya I., Kaygisiz F., Ciftioglu G., Mengi A., Oztabak K. 2009. Associations of growth hormone gene polymorphisms with milk production traits in South Anatolian and East Anatolian red cattle. J. Anim. Vet. Adv. 8: 1040-1044. https://doi.org/10.3923/javaa.2009.1040.1044Youssef Y., Iraqi M., El-Raffa A., Afifi E., Khalil M., García M., et al. 2008. A joint project to synthesize new lines of rabbits in Egypt and Saudi Arabia: emphasis for results and prospects. In Proc.: 9th World Rabbit Congress, 10-13 June, Verona-Italy.Zachmann M. 1992. Interrelations between growth hormone and sex hormones: physiology and therapeutic consequences. Horm. Res. Paediat., 38: 1-8. https://doi.org/10.1159/000182562Zhang W.X., Zhang G.W., Peng J., Lai S.J. 2012. The polymorphism of GHR gene associated with the growth and carcass traits in three rabbit breeds. In Proc.: 10th World Rabbit Congress, Sharm El-Sheikh, Egypt, 75-7

Functional longevity in five rabbit lines founded on different criteria: Comparison at foundation and at fixed times after selection

[EN] The enhancement of rabbit female functional longevity, that is the ability to avoid voluntary culling, is a paramount aspect for the sustainability of meat rabbit production; this trait represents a direct indicator of female robustness. The objective of our study was to compare the functional longevity of five rabbit lines at their foundation and at fixed times during their selection processes. Four of them are maternal lines (A, V, H and LP) selected for litter size at weaning. The fifth line is the paternal line R, founded and selected for post-weaning daily gain from 28 to 63 days. The comparison at foundation involved the complete data set (from March 1980 to March 2013; records of 15,670 does) and pedigree (19,405 animals). Latter comparisons were made when all lines shared the same environmental and management conditions, from March 1997 to September 1998 and from March 2011 to September 2012. In these second comparisons, the same model as that used in the comparison at foundation was used, but now the additive effect was excluded, only data from the corresponding periods were considered. At their foundation, lines V, H and LP showed larger functional longevity than lines A and R, being LP line that with the longest productive life. In the latter comparisons, lines A and R still showing the lowest functional longevities. However, as the selection process evolves, the differences between these two lines and the others were reduced. It could be concluded that the average longevity of a population greatly depends on the criteria followed for its foundation. In addition, along the selection for litter size, the differences of longevity between lines tend to decrease, this is due to an unintended selection for functional longevity, since only offspring from females reaching three parturitions are selected as breeding animals for the next generation.Spanish National Research Plan, Grant/Award Number: AGL2011-30170 C02-01El Nagar, AG.; Baselga, M.; Mínguez, C.; Santacreu, M.; Sánchez, JP. (2021). Functional longevity in five rabbit lines founded on different criteria: Comparison at foundation and at fixed times after selection. Journal of Animal Breeding and Genetics. 138(4):508-517. https://doi.org/10.1111/jbg.12543S508517138

Correction Hierarchically structured iron doped silver Ag Fe lotus flowers for an efficient oxygen reduction reaction

The development of cheap and efficient electrocatalysts for the oxygen reduction reaction ORR is vital for the immediate commercialization of fuel cells which are still limited by the high cost and low performance of the utilized commercial Pt based electrodes. As a promising alternative, this study reports on the synthesis of hierarchical iron doped silver lotus flowers AgFelotus by a facile chemical procedure as robust and efficient ORR electrocatalysts. Succinic acid was used as a structure directing agent to tune the morphology of undoped and iron doped silver particles. In the absence of succinic acid, ball like silver particles were obtained, while using 2 mM succinic acid led to peony like flower structures. The doping of silver peony flowers with iron resulted in lotus like flower structures with high electrocatalytic activity for ORR together with outstanding tolerance against poisoning with various hydrocarbon HC impurities, in situ generated during fuel cell operation, as well as different fuels from anodic crossover. AgFelotus exhibited a superior ORR activity with more than 40 times higher stability than the commercial Pt C catalyst in alkaline media. This substantial performance enhancement is attributed to the unique lotus like flower structures providing more electroactive surface sites, in addition to the iron dopants which facilitate ORR charge transfe

Zinc Oxide Nanoparticles (ZnO-NPs) Suppress Fertility by Activating Autophagy, Apoptosis, and Oxidative Stress in the Developing Oocytes of Female Zebrafish

In vertebrates, the core mechanisms that control gametogenesis are largely multiple, complex, successive, and orchestrated by intrinsic and extrinsic factors. However, age, health status, and hormonal activity are important factors for good fertility; other intangible intracellular molecular mechanisms that manage oocyte development are still unclear. The present study was designed to elucidate the ultrastructure changes in the ovary in response to its exposure to zinc oxide nanoparticles (ZnO-NPs) and to explore the role of autophagy and apoptosis during egg maturation and ovulation on the fertility of female zebrafish. In our study, ZnO-NPs could induce cytotoxicity in the maturing oocyte by activating autophagy and apoptosis in a caspase-dependent manner and could induce oxidative stress by generating reactive oxygen species (ROS) that elevated the mutated ovarian tP53 protein. Simultaneously, necroptosis developed, mimicking the features of apoptosis and necrosis. Collectively, ZnO-NPs created a suitable necrotic environment that led to follicular developmental retardation that altered oocyte ovulation and reduced fecundity of female zebrafish

IN-VITRO EVALUATION OF PROBIOTIC BACTERIA SUPPLEMENTATION TO RUMINANT RATIONS

The aim of this study was to evaluate effect of different level of probiotic supplementation to ruminant rations, using in-vitro batch culture technique to determine degradation and fermentation parameters. In vitro experimental ration was formulated, the ration consisted of 40% alfalfa hay and 60% concentrate feed mixture. Three level of probiotic supplementation (106, 108, 1010 cfu/kg DM) were evaluated. DM and total gas production as well as fermentation parameters of the incubated samples were determined after 24 hrs. of fermentation. Slightly increases (P>0.05) in in-vitro dry matter degradability were observed for the ration supplemented with probiotics bacteria at different levels (106,108 and 1010 cfu/ kg DM) compared to control ration. Probiotics bacteria supplementation with different level (106,108 and 1010 cfu/ kg DM) led to significant (P<0.001) increases in organic matter degradability and total gas production per sample and per g DM, OM, NDF and ADF compared to the not supplemented ration (control ration), and no significant differences were observed among the different levels of probiotics supplementation. Significant increase in total volatile fatty acid concentration after 24 hours' incubation period compared to the not supplemented ration. On the other hand, the treatment supplemented with probiotic recorded lower ammonia concentration compared to the control group. It could be concluded that, adding  probiotics bacteria supplementation to experimental ration resulted increase DM and OM degradability and using dose 106 CFU/kg DM feed is sufficient to induce improvement in degradability and fermentation parameter

Characteristic Evolution and Matching

I review the development of numerical evolution codes for general relativity based upon the characteristic initial value problem. Progress in characteristic evolution is traced from the early stage of 1D feasibility studies to 2D axisymmetric codes that accurately simulate the oscillations and gravitational collapse of relativistic stars and to current 3D codes that provide pieces of a binary black hole spacetime. Cauchy codes have now been successful at simulating all aspects of the binary black hole problem inside an artificially constructed outer boundary. A prime application of characteristic evolution is to extend such simulations to null infinity where the waveform from the binary inspiral and merger can be unambiguously computed. This has now been accomplished by Cauchy-characteristic extraction, where data for the characteristic evolution is supplied by Cauchy data on an extraction worldtube inside the artificial outer boundary. The ultimate application of characteristic evolution is to eliminate the role of this outer boundary by constructing a global solution via Cauchy-characteristic matching. Progress in this direction is discussed.Comment: New version to appear in Living Reviews 2012. arXiv admin note: updated version of arXiv:gr-qc/050809

Eda haplotypes in three-spined stickleback are associated with variation in immune gene expression

Haplotypes underlying local adaptation and speciation are predicted to have numerous phenotypic effects, but few genes involved have been identified, with much work to date concentrating on visible, morphological, phenotypes. The link between genes controlling these adaptive morphological phenotypes and the immune system has seldom been investigated, even though changes in the immune system could have profound adaptive consequences. The Eda gene in three-spined stickleback is one of the best studied major adaptation genes; it directly controls bony plate architecture and has been associated with additional aspects of adaptation to freshwater. Here, we exposed F2 hybrids, used to separate Eda genotype from genetic background, to contrasting conditions in semi-natural enclosures. We demonstrate an association between the Eda haplotype block and the expression pattern of key immune system genes. Furthermore, low plated fish grew less and experienced higher burdens of a common ectoparasite with fitness consequences. Little is currently known about the role of the immune system in facilitating adaptation to novel environments, but this study provides an indication of its potential importance

Interaction between polymorphisms in aspirin metabolic pathways, regular aspirin use and colorectal cancer risk: A case-control study in unselected white European populations

Regular aspirin use is associated with reduced risk of colorectal cancer (CRC). Variation in aspirin’s chemoprevention efficacy has been attributed to the presence of single nucleotide polymorphisms (SNPs). We conducted a meta-analysis using two large population-based case-control datasets, the UK-Leeds Colorectal Cancer Study Group and the NIH-Colon Cancer Family Registry, having a combined total of 3325 cases and 2262 controls. The aim was to assess 42 candidate SNPs in 15 genes whose association with colorectal cancer risk was putatively modified by aspirin use, in the literature. Log odds ratios (ORs) and standard errors were estimated for each dataset separately using logistic regression adjusting for age, sex and study site, and dataset-specific results were combined using random effects meta-analysis. Meta-analysis showed association between SNPs rs6983267, rs11694911 and rs2302615 with CRC risk reduction (All P<0.05). Association for SNP rs6983267 in the CCAT2 gene only was noteworthy after multiple test correction (P = 0.001). Site-specific analysis showed association between SNPs rs1799853 and rs2302615 with reduced colon cancer risk only (P = 0.01 and P = 0.004, respectively), however neither reached significance threshold following multiple test correction. Meta-analysis of SNPs rs2070959 and rs1105879 in UGT1A6 gene showed interaction between aspirin use and CRC risk (Pinteraction = 0.01 and 0.02, respectively); stratification by aspirin use showed an association for decreased CRC risk for aspirin users having a wild-type genotype (rs2070959 OR = 0.77, 95% CI = 0.68–0.86; rs1105879 OR = 0.77 95% CI = 0.69–0.86) compared to variant allele cariers. The direction of the interaction however is in contrast to that published in studies on colorectal adenomas. Both SNPs showed potential site-specific interaction with aspirin use and colon cancer risk only (Pinteraction = 0.006 and 0.008, respectively), with the direction of association similar to that observed for CRC. Additionally, they showed interaction between any non-steroidal anti-inflammatory drugs (including aspirin) use and CRC risk (Pinteraction = 0.01 for both). All gene x environment (GxE) interactions however were not significant after multiple test correction. Candidate gene investigation indicated no evidence of GxE interaction between genetic variants in genes involved in aspirin pathways, regular aspirin use and colorectal cancer risk