BACKGROUND: Colorectal cancer (CRC) is a common, fatal cancer. Identifying subgroups who may benefit more from intervention is of critical public health importance. Previous studies have assessed multiplicative interaction between genetic risk scores and environmental factors, but few have assessed additive interaction, the relevant public health measure. METHODS: Using resources from CRC consortia, including 45,247 CRC cases and 52,671 controls, we assessed multiplicative and additive interaction (relative excess risk due to interaction, RERI) using logistic regression between 13 harmonized environmental factors and genetic risk score, including 141 variants associated with CRC risk. RESULTS: There was no evidence of multiplicative interaction between environmental factors and genetic risk score. There was additive interaction where, for individuals with high genetic susceptibility, either heavy drinking (RERI = 0.24, 95% confidence interval [CI] = 0.13, 0.36), ever smoking (0.11 [0.05, 0.16]), high body mass index (female 0.09 [0.05, 0.13], male 0.10 [0.05, 0.14]), or high red meat intake (highest versus lowest quartile 0.18 [0.09, 0.27]) was associated with excess CRC risk greater than that for individuals with average genetic susceptibility. Conversely, we estimate those with high genetic susceptibility may benefit more from reducing CRC risk with aspirin/nonsteroidal anti-inflammatory drugs use (-0.16 [-0.20, -0.11]) or higher intake of fruit, fiber, or calcium (highest quartile versus lowest quartile -0.12 [-0.18, -0.050]; -0.16 [-0.23, -0.09]; -0.11 [-0.18, -0.05], respectively) than those with average genetic susceptibility. CONCLUSIONS: Additive interaction is important to assess for identifying subgroups who may benefit from intervention. The subgroups identified in this study may help inform precision CRC prevention.

• MeSH
• Diet MeSH
• Adult MeSH
• Genetic Predisposition to Disease * MeSH
• Body Mass Index MeSH
• Gene-Environment Interaction * MeSH
• Polymorphism, Single Nucleotide MeSH
• Colorectal Neoplasms * genetics   epidemiology   MeSH
• Smoking adverse effects   MeSH
• Middle Aged MeSH
• Humans MeSH
• Logistic Models MeSH
• Alcohol Drinking MeSH
• Risk Factors MeSH
• Aged MeSH
• Case-Control Studies MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Genetic screens have been used extensively to probe interactions between nuclear genes and their impact on phenotypes. Probing interactions between mitochondrial genes and their phenotypic outcome, however, has not been possible due to a lack of tools to map the responsible polymorphisms. Here, using a toolkit we previously established in Drosophila, we isolate over 300 recombinant mitochondrial genomes and map a naturally occurring polymorphism at the cytochrome c oxidase III residue 109 (CoIII109) that fully rescues the lethality and other defects associated with a point mutation in cytochrome c oxidase I (CoIT300I). Through lipidomics profiling, biochemical assays and phenotypic analyses, we show that the CoIII109 polymorphism modulates cardiolipin binding to prevent complex IV instability caused by the CoIT300I mutation. This study demonstrates the feasibility of genetic interaction screens in animal mitochondrial DNA. It unwraps the complex intra-genomic interplays underlying disorders linked to mitochondrial DNA and how they influence disease expression.

• MeSH
• Drosophila genetics   MeSH
• Cardiolipins * genetics   metabolism   MeSH
• DNA, Mitochondrial * genetics   metabolism   MeSH
• Mitochondria genetics   metabolism   MeSH
• Electron Transport Complex IV metabolism   MeSH
• Synthetic Lethal Mutations MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Apple (Malus x domestica Borkh.) is one of the most important fruit tree crops of temperate areas, with great economic and cultural value. Apple cultivars can be maintained for centuries in plant collections through grafting, and some are thought to date as far back as Roman times. Molecular markers provide a means to reconstruct pedigrees and thus shed light on the recent history of migration and trade of biological materials. The objective of the present study was to identify relationships within a set of over 1400 mostly old apple cultivars using whole-genome SNP data (~ 253 K SNPs) in order to reconstruct pedigrees. RESULTS: Using simple exclusion tests, based on counting the number of Mendelian errors, more than one thousand parent-offspring relations and 295 complete parent-offspring families were identified. Additionally, a grandparent couple was identified for the missing parental side of 26 parent-offspring pairings. Among the 407 parent-offspring relations without a second identified parent, 327 could be oriented because one of the individuals was an offspring in a complete family or by using historical data on parentage or date of recording. Parents of emblematic cultivars such as 'Ribston Pippin', 'White Transparent' and 'Braeburn' were identified. The overall pedigree combining all the identified relationships encompassed seven generations and revealed a major impact of two Renaissance cultivars of French and English origin, namely 'Reinette Franche' and 'Margil', and one North-Eastern Europe cultivar from the 1700s, 'Alexander'. On the contrary, several older cultivars, from the Middle Ages or the Roman times, had no, or only single, identifiable offspring in the set of studied accessions. Frequent crosses between cultivars originating from different European regions were identified, especially from the nineteenth century onwards. CONCLUSIONS: The availability of over 1400 apple genotypes, previously filtered for genetic uniqueness and providing a broad representation of European germplasm, has been instrumental for the success of this large pedigree reconstruction. It enlightens the history of empirical selection and recent breeding of apple cultivars in Europe and provides insights to speed-up future breeding and selection.

• MeSH
• Breeding MeSH
• Genome, Plant * MeSH
• Genotype MeSH
• Genotyping Techniques methods   MeSH
• Polymorphism, Single Nucleotide genetics   MeSH
• Malus genetics   MeSH
• Pedigree MeSH
• Whole Genome Sequencing MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Europe MeSH

The codling moth Cydia pomonella, a major invasive pest of pome fruit, has spread around the globe in the last half century. We generated a chromosome-level scaffold assembly including the Z chromosome and a portion of the W chromosome. This assembly reveals the duplication of an olfactory receptor gene (OR3), which we demonstrate enhances the ability of C. pomonella to exploit kairomones and pheromones in locating both host plants and mates. Genome-wide association studies contrasting insecticide-resistant and susceptible strains identify hundreds of single nucleotide polymorphisms (SNPs) potentially associated with insecticide resistance, including three SNPs found in the promoter of CYP6B2. RNAi knockdown of CYP6B2 increases C. pomonella sensitivity to two insecticides, deltamethrin and azinphos methyl. The high-quality genome assembly of C. pomonella informs the genetic basis of its invasiveness, suggesting the codling moth has distinctive capabilities and adaptive potential that may explain its worldwide expansion.

• MeSH
• Chromosomes, Insect genetics   MeSH
• Gene Duplication MeSH
• Pheromones metabolism   MeSH
• Genome, Insect MeSH
• Insect Proteins genetics   metabolism   MeSH
• Insecticides pharmacology   MeSH
• Polymorphism, Single Nucleotide MeSH
• Moths drug effects   genetics   metabolism   MeSH
• Promoter Regions, Genetic MeSH
• Receptors, Odorant genetics   metabolism   MeSH
• Insecticide Resistance * MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

KEY MESSAGE: The major quantitative trait loci associated with bunch weight and its component traits in the East African highland banana-breeding population are located on chromosome 3. Bunch weight increase is one of the major objectives of banana improvement programs, but little is known about the loci controlling bunch weight and its component traits. Here we report for the first time some genomic loci associated with bunch weight and its component traits in banana as revealed through a genome-wide association study. A banana-breeding population of 307 genotypes varying in ploidy was phenotyped in three locations under different environmental conditions, and data were collected on bunch weight, number of hands and fruits; fruit length and circumference; and diameter of both fruit and pulp for three crop cycles. The population was genotyped with genotyping by sequencing and 27,178 single nucleotide polymorphisms (SNPs) were generated. The association between SNPs and the best linear unbiased predictors of traits was performed with TASSEL v5 using a mixed linear model accounting for population structure and kinship. Using Bonferroni correction, false discovery rate, and long-range linkage disequilibrium (LD), 25 genomic loci were identified with significant SNPs and most were localized on chromosome 3. Most SNPs were located in genes encoding uncharacterized and hypothetical proteins, but some mapped to transcription factors and genes involved in cell cycle regulation. Inter-chromosomal LD of SNPs was present in the population, but none of the SNPs were significantly associated with the traits. The clustering of significant SNPs on chromosome 3 supported our hypothesis that fruit filling in this population was under control of a few quantitative trait loci with major effects.

• MeSH
• Musa genetics   MeSH
• Phenotype MeSH
• Genetic Association Studies MeSH
• Genetic Markers MeSH
• Genotype MeSH
• Polymorphism, Single Nucleotide MeSH
• Linear Models MeSH
• Quantitative Trait Loci * MeSH
• Fruit growth & development   MeSH
• Plant Breeding * MeSH
• Linkage Disequilibrium MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Africa, Eastern MeSH

Discrimination of particular species within the species complexes of tephritid fruit flies is a very challenging task. In this fruit-fly family, several complexes of cryptic species have been reported, including the African cryptic species complex (FAR complex). Cuticular hydrocarbons (CHCs) appear to be an excellent tool for chemotaxonomical discrimination of these cryptic species. In the present study, CHC profiles have been used to discriminate among three important agricultural pests from the FAR complex, Ceratitis fasciventris, Ceratitis anonae and Ceratitis rosa. Hexane body surface extracts of mature males and females were analyzed by two-dimensional gas chromatography with mass spectrometric detection and differences in CHC profiles between species and sexes tested through multivariate statistics and compared with species identification by means of microsatellite markers. Quantitative as well as qualitative CHC profile differences between sexes and species are reported. The CHC profiles consisted of a mixture of linear, internally methyl-branched and mono-, di- and tri-unsaturated alkanes. Twelve compounds were pinpointed as potential chemotaxonomical markers. The present study shows that presence or absence of particular CHCs might be used in the chemical diagnosis of the FAR complex. Moreover, our results represent an important first step in the development of a useful chemotaxonomic tool for cryptic species identification of these important agricultural pests.

• MeSH
• Species Specificity MeSH
• Genotype MeSH
• Insect Proteins chemistry   MeSH
• Classification methods   MeSH
• Microsatellite Repeats MeSH
• Sex Characteristics MeSH
• Polymorphism, Genetic MeSH
• Tephritidae chemistry   classification   MeSH
• Hydrocarbons chemistry   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

BACKGROUND: Treatment with 5-fluorouracil (5-FU) is known to improve survival in many cancers including colorectal cancer. Response to the treatment, overall survival and recurrence show inter-individual variation. METHODS: In this study we employed a strategy to search eQTL variants influencing the expression of a large number of genes. We identified four single nucleotide polymorphisms, defined as master regulators of transcription, and genotyped them in a set of 218 colorectal cancer patients undergoing adjuvant 5-FU based therapy. RESULTS: Our results showed that the minor allele variant of the rs4846126 polymorphism was associated with poor overall and progression-free survival. Patients that were homozygous for the variant allele showed an over two fold increased risk of death (HR 2.20 95%CI 1.05-4.60) and progression (HR 2.88, 95% 1.47-5.63). The integration of external information from publicly available gene expression repositories suggested that the rs4846126 polymorphism deserves further investigation. This variant potentially regulates the gene expression of 273 genes with some of them possibly associated to the patient's response to 5-FU treatment or colorectal cancer. CONCLUSIONS: Present results show that mining of public data repositories in combination with own data can be a fruitful approach to identify markers that affect therapy outcome. In particular, a genetic screen of master regulators may help in order to search for the polymorphisms involved in treatment response in cancer patients.

• MeSH
• Chemotherapy, Adjuvant MeSH
• Adult MeSH
• Fluorouracil administration & dosage   MeSH
• Genetic Association Studies MeSH
• Polymorphism, Single Nucleotide * MeSH
• Colorectal Neoplasms drug therapy   genetics   mortality   surgery   MeSH
• Combined Modality Therapy MeSH
• Quantitative Trait, Heritable * MeSH
• Leucovorin administration & dosage   MeSH
• Middle Aged MeSH
• Humans MeSH
• Antineoplastic Combined Chemotherapy Protocols therapeutic use   MeSH
• Gene Expression Regulation, Neoplastic genetics   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Transcription Factors genetics   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

The interplay between dietary habits and individual genetic make-up is assumed to influence risk of cancer, via modulation of DNA integrity. Our aim was to characterize internal and external factors that underlie inter-individual variability in DNA damage and repair and to identify dietary habits beneficial for maintaining DNA integrity. Habitual diet was estimated in 340 healthy individuals using a food frequency questionnaire and biomarkers of antioxidant status were quantified in fasting blood samples. Markers of DNA integrity were represented by DNA strand breaks, oxidized purines, oxidized pyrimidines and a sum of all three as total DNA damage. DNA repair was characterized by genetic variants and functional activities of base and nucleotide excision repair pathways. Sex, fruit-based food consumption and XPG genotype were factors significantly associated with the level of DNA damage. DNA damage was higher in women (p=0.035). Fruit consumption was negatively associated with the number of all measured DNA lesions, and this effect was mediated mostly by β-cryptoxanthin and β-tocopherol (p<0.05). XPG 1104His homozygotes appeared more vulnerable to DNA damage accumulation (p=0.001). Sex and individual antioxidants were also associated with DNA repair capacity; both the base and nucleotide excision repairs were lower in women and the latter increased with higher plasma levels of ascorbic acid and α-carotene (p<0.05). We have determined genetic and dietary factors that modulate DNA integrity. We propose that the positive health effect of fruit intake is partially mediated via DNA damage suppression and a simultaneous increase in DNA repair capacity.

• MeSH
• Antioxidants metabolism   MeSH
• DNA-Binding Proteins genetics   metabolism   MeSH
• Adult MeSH
• Endonucleases genetics   metabolism   MeSH
• Genetic Variation MeSH
• Genetic Markers MeSH
• Gene-Environment Interaction MeSH
• Nuclear Proteins genetics   metabolism   MeSH
• Polymorphism, Single Nucleotide MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• DNA Repair * MeSH
• DNA Damage genetics   MeSH
• Aged MeSH
• Sex Factors MeSH
• Feeding Behavior * MeSH
• Transcription Factors genetics   metabolism   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Norway MeSH

Východiska: Při studiu vztahů mezi kouřením a rakovinou prsu dosud nebyly nalezeny jednoznačné výsledky – ně­kte­ré studie konstatovaly, že kouření je faktorem rizikovým, zatímco jiné shledaly jeho účinky protektivní. Cíl: Novější studie nabízejí vysvětlení těchto rozdílů genetickým polymorfizmem. Cigaretový kouř obsahuje minimálně 20 chemických karcinogenů, jejichž cílovým orgánem je prsní žláza a okolní tuková tkáň, v níž se metabolicky aktivují a ukládají. Tyto látky a jejich metabolity se vyskytují v sekretu z prsní žlázy i jako specifické addukty DNA ve tkáni prsu. Mnohé studie shodně popisují signifikantní zvýšení rizika rakoviny prsu u kuřaček, které začaly kouřit v mladém věku a/nebo před prvním těhotenstvím. Statisticky významné zvýšení rizika rakoviny prsu u žen dlouhodobě exponovaných pasivnímu kouření potvrdily prospektivní longidutinální studie z Japonska, Číny, Kalifornie, mnozí odborníci však tyto výsledky zpochybňují. Případný protektivní vliv kouření na incidenci zhoubných nádorů prsu je přisuzován antiestrogenním účinkům kouření, resp. nikotinu. Závěr: Kouření pravděpodobně má rizikovou roli v iniciaci nádorů prsu. Vzhledem k širokému spektru škodlivých účinků kouření i k horší prognóze vývoje rakoviny prsu u kuřaček jsou preferována všeobecně známá doporučení i pro prevenci rakoviny prsu – nekouřit, nepít alkohol, konzumovat ovoce a zeleninu, být fyzicky aktivní, udržovat správnou hmotnost.

Background: Investigation of the relationship between smoking and breast cancer risk did not show a consensus in results – some studies described smoking as a risk factor, while others found its effects protective. Purpose: The newest studies explain these differences by the genetic polymorphism. Cigarette smoke contains at least 20 chemical carcinogens, which are deposited and metabolically activated in the breast and surrounding adipose tissues. The substances are further detected in the nipple discharge or as smoking‑specific DNA adducts in breast tissue. Several studies postulate significantly higher risk of breast cancer among women who started smoking at an early age and/or before their first delivery. Some studies from Japan, China, California have shown that long‑term exposure to passive smoking could significantly increase the risk of breast cancer in never smokers, while other scientist reject the evidence of this association as inconsistent. A possible protective effect of smoking on the incidence of breast cancer is explained by antiestrogenic activity of smoking, namely nicotine. Conclusion: Smoking may play a role in the breast cancer incidence. Due to a wide spectrum of harmful effects of smoking, and with regards to the worse prognosis of breast cancer among smoking patients, the common recommendations for cancer prevention are similarly plausible in case of breast cancer – no‑smoking, no alcohol, fruit and vegetable consumption, physical activity and body weightcontrol. Key words: smoking – breast neoplasms – epidemiologic studies The author declare she has no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers. Submitted: 17. 6. 2013 Accepted: 27. 6. 2013

• MeSH
• Adult MeSH
• Estrogens MeSH
• Risk Assessment * MeSH
• Clinical Trials as Topic MeSH
• Smoking * MeSH
• Humans MeSH
• Menarche MeSH
• Meta-Analysis as Topic MeSH
• Adolescent MeSH
• Young Adult MeSH
• Breast Neoplasms * etiology   genetics   prevention & control   MeSH
• Nicotine MeSH
• Polymorphism, Genetic * MeSH
• Prospective Studies MeSH
• Risk Factors MeSH
• Age Factors MeSH
• Tobacco Smoke Pollution * adverse effects   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Female MeSH

Nebylo prokázáno, že umělé přísady stravy jsou příčinou ADHD, avšak některé studie ukazují, že určitá umělá barviva a konzervanty v potravě mohou být příčinou zhoršení hyperaktivního chování u některých dětí. Stevenson et al.12 sledovali ve dvojitě slepé, zkřížené studii s placebem účinek dvou směsí umělých barviv a benzoátu sodného podávaných v ovocném nápoji 297 dětem ze vzorku obecné populace. Nežádoucí účinek přídavků stravy na ADHD symptomy byl ovlivňován degradací histaminu v důsledku genetického polymorfismu HNMT T939C a Thrl05Ile. Varianty genů ovlivňující aktivitu histaminu mohou vysvětlit inkonzistentní výsledky mezi předchozími studiemi.

There's no evidence that food additives cause attention-deficit/hyperactivity disorder (ADHD), but some studies show that certain food colorings and preservatives may cause or worsen hyperactive behavior in some children. Stevenson et al.12 studied in a double-blind, placebo controlled crossover trial that involved two food color additives and sodium benzoate mixtures in fruit drink administred to a general community sample of 297 children. The adverse effect of food additives on ADHD symptoms was moderated by histamine degradation gene polymorphisms of histamine N-methyltransferase (HNMT T939C and Thrl05Ile). Variations of genes influencing the action of histamine may explain the inconsistency of results in previous studies.

• Keywords
• ADHD, umělé přísady stravy,
• MeSH
• Behavioral Symptoms MeSH
• Diet MeSH
• Child MeSH
• Genetics MeSH
• Histamine N-Methyltransferase genetics   MeSH
• Histamine MeSH
• Attention Deficit Disorder with Hyperactivity etiology   MeSH
• Clinical Trials as Topic MeSH
• Humans MeSH
• Polymorphism, Genetic genetics   MeSH
• Food Additives adverse effects   MeSH
• Child, Preschool MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Child, Preschool MeSH
• Publication type
• Review MeSH