Perturbations in gut and respiratory microbiota in COVID-19 and influenza patients: a systematic review and meta-analysis.

Objectives: Coronavirus disease-19 (COVID-19)/influenza poses unprecedented challenges to the global economy and healthcare services. Numerous studies have described alterations in the microbiome of COVID-19/influenza patients, but further investigation is needed to understand the relationship between the microbiome and these diseases. Herein, through systematic comparison between COVID-19 patients, long COVID-19 patients, influenza patients, no COVID-19/influenza controls and no COVID-19/influenza patients, we conducted a comprehensive review to describe the microbial change of respiratory tract/digestive tract in COVID-19/influenza patients. Methods: We systematically reviewed relevant literature by searching the PubMed, Embase, and Cochrane Library databases from inception to August 12, 2023. We conducted a comprehensive review to explore microbial alterations in patients with COVID-19/influenza. In addition, the data on α-diversity were summarized and analyzed by meta-analysis. Results: A total of 134 studies comparing COVID-19 patients with controls and 18 studies comparing influenza patients with controls were included. The Shannon indices of the gut and respiratory tract microbiome were slightly decreased in COVID-19/influenza patients compared to no COVID-19/influenza controls. Meanwhile, COVID-19 patients with more severe symptoms also exhibited a lower Shannon index versus COVID-19 patients with milder symptoms. The intestinal microbiome of COVID-19 patients was characterized by elevated opportunistic pathogens along with reduced short-chain fatty acid (SCFAs)-producing microbiota. Moreover, Enterobacteriaceae (including Escherichia and Enterococcus) and Lactococcus, were enriched in the gut and respiratory tract of COVID-19 patients. Conversely, Haemophilus and Neisseria showed reduced abundance in the respiratory tract of both COVID-19 and influenza patients. Conclusion: In this systematic review, we identified the microbiome in COVID-19/influenza patients in comparison with controls. The microbial changes in influenza and COVID-19 are partly similar.

Avian influenza A virus H7N9 in China, a role reversal from reassortment receptor to the donator.

Reassortment can introduce one or more gene segments of influenza A viruses (IAVs) into another, resulting in novel subtypes. Since 2013, a new outbreak of human highly pathogenic avian influenza has emerged in the Yangtze River Delta (YRD) and South-Central regions of China. In this study, using Anhui province as an example, we discuss the possible impact of H7N9 IAVs on future influenza epidemics through a series of gene reassortment events. Sixty-one human H7N9 isolates were obtained from five outbreaks in Anhui province from 2013 to 2019. Bioinformatics analyses revealed that all of them were characterized by low pathogenicity and high human or mammalian tropism and had introduced novel avian influenza A virus (AIV) subtypes such as H7N2, H7N6, H9N9, H5N6, H6N6, and H10N6 through gene reassortment. In reassortment events, Anhui isolates may donate one or more segments of HA, NA, and the six internal protein-coding genes for the novel subtype AIVs. Our study revealed that H7N9, H9N2, and H5N1 can serve as stable and persistent gene pools for AIVs in the YRD and South-Central regions of China. Novel AIV subtypes might be generated continuously by reassortment. These AIVs may have obtained human-type receptor-binding abilities from their donors and prefer binding to them, which can cause human epidemics through accidental spillover infections. Facing the continual threat of emerging avian influenza, constant monitoring of AIVs should be conducted closely for agricultural and public health.

The Efficacy of Senna Bowel Preparation for Colonoscopy: A Systematic Review and Meta-analysis.

The quality of bowel preparation is an extremely important determinant of colonoscopy results. However, the efficacy of senna regimens in improving bowel cleanliness is uncertain. We conducted a systematic review and meta-analysis to synthesize data on whether using a senna bowel preparation regimen enhances the bowel cleanliness. We searched Web of Science Core Collection, MEDLINE, PubMed, Embase, Cochrane Library, and Scopus databases (from the inception to August 2021). The primary efficacy outcome was bowel cleanliness. Secondary outcomes included patient compliance, tolerance, and adverse events. Eleven trials fulfilled the inclusion criteria (3,343 patients. Overall, we found no significant differences in bowel cleanliness between the senna regimen and other bowel preparation regimens (odds ratio [95% confidence interval]: 1.02 [0.63, 1.67], p = 0.93). There was significant difference in tolerance (odds ratio [95% confidence interval]: 1.66 [1.08, 2.54], p = .02) and compliance (odds ratio [95% confidence interval]: 3.05 [1.42, 6.55], p = .004). The senna regimen yielded a significantly greater proportion of no nausea (odds ratio [95% confidence interval]: 1.84 [1.45, 2.32]) and vomiting (odds ratio [95% confidence interval]: 1.65 [0.81, 3.35]). Compared with other bowel preparation regimens, the senna regimen may be effective and safe in bowel cleaning before colonoscopy, with superior compliance and tolerance.

The Epidemiological Pattern and Co-infection of Influenza A and B by Surveillance Network From 2009 to 2014 in Anhui Province, China.

Influenza-like illness (ILI) is one of the most important public health problems globally, causing an enormous disease burden. Influenza infections are the most common cause of ILI. Bacterial and virus co-infection is common yet the data of co-infection with influenza A and B viruses are scarce. To identify the epidemiological patterns of and co-infection of influenza A and B in Anhui province, China, we analyzed the surveillance data of 5 years from 2009 to 2014 collected by the Chinese National influenzas network. The results showed that the weekly ratio of ILI was 3.96 ± 1.9% (95% CI 3.73-4.2%) in outpatients and the highest affected population was children under 5 years old. The epidemic of influenza viruses was highest during 2009-2010. For the other 4 surveillance years, school-aged people (5-14 years) were the most highly affected population. Influenza B and H3N2 viruses were more prevalent than H1N1pdm09 virus after 2010. In addition, a significant co-circulation of influenza A (H1N1pdm09 and H3N2) and influenza B virus was detected with 0.057% PCR positive rate during 2009-2014 in Eastern China, yet isolated only in pediatric patients. Our data reveals school-aged population would be the main vulnerable population and a distinct seasonality for influenza. In addition, the co-infection of influenza A and B were found in Anhui Province, China. Ongoing surveillance is critical to understand the seasonality variation and make evidence-based vaccination recommendations. Information on the epidemiological patterns and co-infections of influenza A and B can help us to implement different strategies for selecting vaccine formulations and monitoring new emerging influenza strains. In addition, the identification of the susceptible population can help us to develop more precise protection measures.

Changes in Serum Neutralizing Antibodies Levels During Convalescence of COVID-19 Patients.

Detection of serum-specific SARS-CoV-2 antibody has become a complementary means for the identification of coronavirus disease 2019 (COVID-19). As we already know, the neutralizing antibody titers in patients with COVID-19 decrease during the course of time after convalescence, whereas the duration of antibody responses in the convalescent patients has not been defined clearly. In the current study, we collected 148 serum samples from 37 confirmed COVID-19 cases with different disease severities. The neutralizing antibodies (Nabs), IgM and IgG against COVID-19 were determined by CLIA Microparticle and microneutralization assay, respectively. The time duration of serum titers of SARS-CoV-2 antibodies were recorded. Our results indicate that IgG (94.44%) and Nabs (89.19%) can be detected at low levels within 190-266 days of disease onset. The findings can advance knowledge regarding the antibody detection results for COVID-19 patients and provide a method for evaluating the immune response after vaccination.

Epidemiological and clinical features of SARS-CoV-2 cluster infection in Anhui Province, Eastern China.

BACKGROUND: COVID-19 has spread worldwide and become a pandemic. We report the epidemiological and clinical characteristics of cluster infections. METHODS: Data of clustered cases were retrieved from the public health emergency monitoring information system of China. We analyzed the incubation period, generation gap, secondary attack rate, and viral load in various grouped cases. RESULTS: A total of 60 COVID-19 infection clusters including 226 patients and 19 asymptomatic cases involving four generations were analyzed. With the increase of transmission generations, secondary attack rate decreased (P＜0.001) and severity alleviated (P = 0.008). The median incubation period and intergenerational interval were 9 and 6 days, respectively. The secondary attack rate was 7.1% in the index cases, 5.0% in the first generation, 1.0% in the second generation, and 4.7% overall. Severe cases were seen more in the index (13, 65%) and first generation (7, 35%) ones, who had a significantly higher viral load than the mild and moderate ones. CONCLUSIONS: With the increase of transmission generation, secondary infection rate and severity decreased. Severe patients had a higher virus load. Patients in the incubation period and asymptomatic carriers were potential infection sources who might play an important role in transmission.

Emergence of a young case infected with avian influenza A (H5N6) in Anhui Province, East China during the COVID-19 pandemic.

In the context of the coronavirus disease 2019 pandemic, we investigated the epidemiological and clinical characteristics of a young patient infected by avian influenza A (H5N6) virus in Anhui Province, East China, and analyzed genomic features of the pathogen in 2020. Through the cross-sectional investigation of external environment monitoring (December 29-31, 2020), 1909 samples were collected from Fuyang City. It was found that the positive rate of H5N6 was higher than other areas obviously in Tianma poultry market, where the case appeared. In addition, dual coinfections were detected with a 0.057% polymerase chain reaction positive rate the surveillance years. The virus was the clade 2.3.4.4, which was most likely formed by genetic reassortment between H5N6 and H9N2 viruses. This study found that the evolution rates of the hemagglutinin and neuraminidase genes of the virus were higher than those of common seasonal influenza viruses. The virus was still highly pathogenic to poultry and had a preference for avian receptor binding.

The contrasting relationships of relative humidity with influenza A and B in a humid subtropical region.

Influenza is an acute respiratory disease that seriously threatens public health. The occurrence of influenza has been proved to be related to a variety of meteorological factors. However, less attention has been paid to the effect of relative humidity (RH) on different types of influenza, especially in subtropical regions. Daily data on laboratory-confirmed influenza cases, weather variables, and air pollutants in Hefei covering the 2014-2019 period were collected. The seasonality and trend of daily influenza cases were explored by the time series seasonal decomposition method. Generalized linear model was fitted in conjunction with distributed lag nonlinear model to quantify the associations of RH with influenza A and influenza B. Subgroup analyses were conducted by sex, age (0-4, 5-17, and ≥18 years), and season (cold and warm seasons). A total of 5238 influenza cases including 2847 influenza A cases and 2391 influenza B cases were recorded. The epidemic of influenza presented a distinct seasonal pattern, and the number of daily influenza cases increased steadily since 2016. High RH was related to an increased risk of influenza A (maximum RR = 1.683, 95%CI: 1.365-2.076), especially among males, females, and school-age children. Low RH was associated with an increased risk of influenza B (maximum RR = 1.252, 95%CI: 1.169-1.340). The contrasting relationships of RH with influenza A and B remained significant in cold seasons. High RH and low RH were significantly associated with the increased risk of influenza A and B, respectively. The findings of our study may provide clues for proposing new effective interventions.

Molecular characteristics of the H9N2 avian influenza viruses in live poultry markets in Anhui Province, China, 2013 to 2018.

BACKGROUND AND AIMS: H9N2 subtype avian influenza virus (AIV) has low-pathogenicity but causes respiratory symptoms and drop in egg production in chicken with long-term virus shedding, resulting in great economic losses due to high mortality related to secondary infection with other pathogens. In recent years, H9N2 viruses have been posing a threat to public health, causing human infection in China. Compared to studies on other AIV subtypes, there are relatively few studies on the pathogenic mechanism of the H9N2 virus in mammals. H9N2 subtype AIV has been circulating worldwide in many avian species and transmitting with high efficiency in poultry. It can provide internal genes for other subtypes to produce new viruses, causing a pandemic risk. It is important to carry out long-term surveillance and pathogenic characteristics of the H9N2 virus. In this study, we conducted environmental surveillance of live poultry markets in Anhui province from 2013 to 2018, and 33 representative environmental isolates were selected and studied systematically. METHODS: The genomic RNA of Anhui H9N2 isolates was subjected to RT-PCR amplification followed by sequencing analysis. RESULTS: Thirty-three strains were isolated from the embryonated eggs of specific-pathogen-free chickens. Phylogenetic analysis indicated that h9.4.2.5-like H9N2 viruses were predominant during 2013-2018 and acquired multiple specific amino acid mutations that may have increased their affinity for mammals and enhanced their infectivity and transmissibility. Additionally, six internal genes of H9N2 clustered together with the novel human-lethal reassortant viruses, such as the low-pathogenicity H7N9, H10N8, and Anhui H5N6 viruses, and even HPAI H7N9. CONCLUSION: Because H9N2 viruses may be the donors of internal genes that lead to the generation of novel reassortant viruses with enhanced pathogenicity in Anhui province, continuous environmental surveillance of live poultry markets, a key source of reassorted H9N2 and other avian influenza viruses, is of great importance.

Molecular epidemiology of SARS-CoV-2 clusters caused by asymptomatic cases in Anhui Province, China.

BACKGROUND: COVID-19 is a newly emerging disease caused by a novel coronavirus (SARS-CoV-2), which spread globally in early 2020. Asymptomatic carriers of the virus contribute to the propagation of this disease, and the existence of asymptomatic infection has caused widespread fear and concern in the control of this pandemic. METHODS: In this study, we investigated the origin and transmission route of SARS-CoV-2 in Anhui's two clusters, analyzed the role and infectiousness of asymptomatic patients in disease transmission, and characterized the complete spike gene sequences in the Anhui strains. RESULTS: We conducted an epidemiological investigation of two clusters caused by asymptomatic infections sequenced the spike gene of viruses isolated from 12 patients. All cases of the two clusters we investigated had clear contact histories, both from Wuhan, Hubei province. The viruses isolated from two outbreaks in Anhui were found to show a genetically close link to the virus from Wuhan. In addition, new single nucleotide variations were discovered in the spike gene. CONCLUSIONS: Both clusters may have resulted from close contact and droplet-spreading and asymptomatic infections were identified as the initial cause. We also analyzed the infectiousness of asymptomatic cases and the challenges to the current epidemic to provided information for the development of control strategies.

Sporadic occurrence of H9N2 avian influenza infections in human in Anhui province, eastern China: A notable problem.

H9N2 viruses can cause great economic losses to the domestic poultry industry when co-infected with other influenza viruses or pathogens. . To better understand the molecular characteristics of H9N2 avian influenza viruses (AIVs) and analyze the genetic evolutionary relationship, we isolated three H9N2 subtypes AIVs from nasopharyngeal swab specimens from the three cases reported in Anhui province since 2015, and systematically reviewed the genome-wide data of 21 poultry--isolated H9N2 viruses during 1998-2017. The six internal genes of three human-isolated viruses and recent poultry-isolated viruses (since 2014) in Anhui province presented high gene homologies with HPAI H7N9, even including H10N8 and H5N6. The three human-isolated H9N2 AIVs and poultry-isolated viruses (since 2008) in Anhui province were highly similar, and classified into genotype S. Seven N-linked potential glycosylation sites in the HA protein were detected in the three human-isolated viruses, which also appeared in poultry-isolated H9N2 AIVs. None of the human-isolated H9N2 AIVs had the I368V mutation in PB1 protein, but all the poultry-isolated H9N2 viruses in 2017 carried this mutation. Multidisciplinary, cross-regional and cross-sectoral approaches are warranted to address complex public health challenges and achieve the goal of 'one health'.

Identifying Infectious Diarrhea Hot spots and Associated Socioeconomic Factors in Anhui Province, China.

Infectious diarrhea cases have increased during the past years in the Anhui Province of China, but little is known about its spatial cluster pattern and associated socioeconomic factors. We obtained county-level total cases of infectious diarrhea in 105 counties of Anhui in 2016 and computed age-adjusted rates. Socioeconomic factors were collected from the Statistical Yearbook. Hot spot analysis was used to identify hot and cold spot counties for infectious diarrhea incidence. We then applied binary logistic regression models to determine the association between socioeconomic factors and hot spot or cold spot clustering risk. Hot spot analysis indicated there were both significant hot spot (29 counties) and cold spot (18 counties) clustering areas for infectious diarrhea in Anhui (P < 0.10). Multivariate binary logistic regression results showed that infectious diarrhea hot spots were positively associated with per capita gross domestic product (GDP), with an adjusted odds ratio (AOR): 3.51, 95% CI: 2.09-5.91, whereas cold spots clustering were positively associated with the number of medical staffs (AOR: 1.18, 95% CI: 1.08-1.29) and negatively associated with the number of public health physicians (AOR: 0.27, 95% CI: 0.09-0.86). We identified locations for hot and cold spot clusters of infectious diarrhea incidence in Anhui, and the clustering risks were significantly associated with health workforce resources and the regional economic development. Targeted interventions should be carried out with considerations of regional socioeconomic conditions.

Short-term effects of moderate and severe floods on infectious diarrheal diseases in Anhui Province, China.

BACKGROUND: Previous studies showed that floods can lead to diarrheal diseases outbreaks; however, the short-term effects of different severity floods on diarrheal diseases are not clear. This study aims to examine 0-14 days lagged effects of moderate and severe floods on diarrhea in Anhui Province, one heavily flood-prone area in China. METHODS: Daily diarrheal cases from January 1, 2013 to August 31, 2017 in 16 cities of Anhui were extracted from the National Notifiable Disease Surveillance System. Meteorological data were obtained, and moderate or severe floods were identified according to Comprehensive Study Group of Major Natural Disasters of the State Science and Technology Commission in China. The quasi-Poisson generalized linear models were applied to evaluate effects of floods on daily diarrheal cases in each city with 0-14 days lag, and we divided post-flood periods into week 1 and week 2, further conducted provincial-level meta-analysis. RESULTS: Immediate effects of floods on diarrheal diseases were observed within 7 days, and at provincial level moderate floods had a RR of 1.05 (95% CI: 1.02-1.09) and severe floods RR = 1.04 (95% CI: 1.01-1.08) controlling for population size, temperature and relative humidity etc., but less effects appeared in the second week. Impacts of flooding on diarrheal diseases varied among cities. Moderate floods in week 1 had a RR of 1.51 (95% CI: 1.29-1.78) in Bozhou, and severe floods had a RR = 1.31 (95% CI: 1.05-1.64) in Chuzhou. The severe floods may have higher RR in week 1 compared with moderate floods in Anqing (1.10 vs 1.06), Chuzhou (1.31 vs 1.07) and Luan (1.18 vs 1.00). CONCLUSIONS: Both moderate and severe floods can significantly increase diarrheal risks in one week with regionally varied effects, and severe floods may lead higher risks. The findings have implications for preparing emergent interventions in hazard periods to reduce health risks of floods.

Genetic characterization of the first detected human case of avian influenza A (H5N6) in Anhui Province, East China.

We compared complete genome sequences of two strains of an avian influenza A (H5N6) virus isolated from a patient in Anhui Province with those of other strains from GenBank and Global initiative on sharing all influenza data (GISAID). The HA gene of the isolated virus shared homology with that of A/chicken/Zhejiang/727155/2014 (H5N6) at the level of similarity of 98%. The six internal genes of the Anhui strains were close to those of H9N2 viruses from Zhejiang, Shandong, and Guangdong provinces, with a similarity of 99%. In addition, the similarity between the internal antigens (NP and MP) of the isolated H5N6 virus and H7N9 and H10N8 viruses was 99%. Based on the data of phylogenetic analysis, the H5N6 influenza virus isolated in Anhui Province belonged to clade 2.3.4.4. The virus was shown to have molecular characteristics of highly pathogenic avian influenza viruses, including eight glycosylation sites and an amino acid sequence of the HA protein cleavage site, PLRERRRKKR/GLF, containing multiple basic amino acids. Additionally, the stalk domain of the NA protein was found to have a deletion in NA stalk region (11 amino acids in N6, positions 58-68). Our study demonstrated that the H5N6 virus from Anhui Province represented a triple-reassortant virus and could be highly pathogenic to humans. The prevalence of this virus should be closely monitored.

[Establishment and application of public health risk assessment indexes for flood disaster].

OBJECTIVE: To establish a public health risk assessment indexes for flood disaster. METHODS: Delphi method and expert consultation were used to establish the public health risk assessment index system and scoring criteria, and the analytic hierarchy process (AHP) method was used to obtain the weight of the indexes. Then, the established index system was applied to evaluate the public health risk of the flood disaster in Anhui province, 2016. RESULTS: A public health risk assessment system consisting of 5 categories and 17 indexes was constructed. The assessment result of the flood disaster in Anhui province of 2016 showed that the public health risk score was 0.26, suggesting that "the health emergency measures were effective, and the public health risks were effectively controlled". CONCLUSIONS: The established indexes can effectively assess the health risk of flood disaster and also can provide the reference for other disaster assessment.

The human T-cell cloning assay: identifying genotypes susceptible to drug toxicity and somatic mutation.

Humans exhibit marked genetic polymorphisms in drug metabolism that contribute to high incidence of adverse effects in susceptible individuals due to altered balance between metabolic activation and detoxification. The T-cell cloning assay, which detects mutations in the gene for hypoxanthine-guanine phosphoribosyl transferase (HPRT), is the most well-developed reporter system for studying specific locus mutation in human somatic cells. The assay is based on a mitogen- and growth factor-dependent clonal expansion of peripheral T-lymphocytes in which the 6-thioguanine-resistant HPRT mutants can be selected, enumerated, and collected for molecular analysis of the mutational nature. The assay provides a unique tool for studying in vivo and in vitro mutagenesis, for investigating the functional impact of common polymorphism in metabolism and repair genes, and for identifying risk genotypes for drug-induced toxicity and mutagenicity. This chapter presents a simple and reliable method for the enumeration of HPRT mutant frequency induced in vitro without using any source of recombinant interleukin-2. The other main feature is that only truly induced and unique mutants are collected for further analysis.

The (CCTTT)n microsatellite polymorphism in the NOS2 gene may influence lung cancer risk and long-term survival, especially in non-smokers.

We analyzed the associations of the NOS2 (CCTTT)n promoter polymorphism to lung cancer risk and tumor histology in smokers and non-smokers. We also investigated lung cancer long-term survival in relation to the polymorphism, smoking data, histology, age at diagnosis, and gender. One hundred eighty-five lung-cancer patients and 164 matched controls, where non-smokers were enriched among the lung cancer cases, were genotyped by fragment analysis and sequencing. Genotypes were combined with information on histology, patient smoking status, and cancer-specific death, using a 20-year follow-up. We divided the (CCTTT)n alleles into short (n ≤ 10), intermediate (n = 11-12), and long (n ≥ 13). Patients homozygous for short repeats had significantly increased risk of lung cancer (p = 0.030) compared to carriers of two long alleles (LL). Lack of long allele was associated with a significantly increased lung cancer risk overall (p = 0.011), especially among non-smokers (p = 0.001). A significantly higher lung cancer survival was seen in non-smokers compared to smokers (p = 0.046) and in low-dose smokers compared to high-dose smokers at the time of diagnosis (p = 0.028). Moreover, non-smoking patients with squamous cell carcinoma (p = 0.015) or adenocarcinoma (p = 0.024) showed a significantly lower survival compared to other lung carcinomas. Nitric oxide can induce proliferation as well as apoptosis depending on cellular context. Our results suggest that the (CCTTT)n NOS2 microsatellite may influence the risk of developing lung cancer, especially in non-smokers, possibly by affecting intracellular nitric oxide levels. Our results also give additional information about the yet poorly understood etiological and prognostic differences between lung cancer in non-smokers and smokers.

PADI4 polymorphisms and susceptibility to rheumatoid arthritis: a meta-analysis.

The objective of the study was to investigate the association between peptidylarginine deiminase 4 (PADI4) polymorphism and susceptibility to rheumatoid arthritis (RA). An electronic searching strategy was employed to collect relevant studies on the association between PADI4 polymorphism and susceptibility to RA. The odds ratio (OR) with the 95 % confidence interval (95 % CI) was used to evaluate the RA risk presented by PADI4 polymorphism. Fixed or random effects models were selected based on heterogeneity. Publication bias was assessed using funnel plots, Begg's test, and Egger's test. A total of 27 studies from 21 articles were included. Six gene loci (padi4_94, 104, 92, 90, 89, and 100) were chosen for the meta-analysis. The pooled ORs (95 % CI) for allele 2 versus 1 were 1.08 (1.05-1.12), 1.17 (1.12-1.23), 1.26 (1.18-1.36), 1.17 (1.10-1.24), 1.30 (1.17-1.44), and 1.25 (1.11-1.40), respectively. All six SNPs were significantly associated with RA in Asian populations. Three SNPs (PADI4_104, 90, 89) showed significant associations, while the other three SNPs (PADI4_94, 92, 100) exhibited no associations in the European population. A dose-response relationship between allele 2 of PADI4 and the risk of RA was also identified. In conclusion, this meta-analysis suggests that PADI4 polymorphisms represent a significant risk factor for RA, especially in Asians.

Polymorphisms in the DNA repair genes XRCC1, APEX1, XRCC3 and NBS1, and the risk for lung cancer in never- and ever-smokers.

This case-control study examines the association between lung cancer and genetic polymorphisms in two base excision repair (BER) genes, XRCC1 and APEX1 and two genes involved in homologous recombination repair (HR), XRCC3 and NBS1. Never-smoking lung cancer patients were recruited, and also the next diagnosed ever-smoking case of the same gender and age group. Controls were recruited from the regional population register, frequency matched to cases by hospital catchment area, gender, age group and smoking category. As a result more than 70% of the study population were women. A total of 331 individuals were analysed. Presence of the XRCC1 399Gln allele was associated with a significantly decreased risk for lung cancer among non-smoking women (odds ratio (OR) 0.4, 95% confidence interval (CI) 0.2-0.9). No significant effect was seen with the APEX1 polymorphism. Women smokers carrying the XRCC3 241Met allele showed a significantly decreased risk for lung cancer (OR 0.3, CI 0.2-0.7). The NBS1 185Gln allele was significantly associated with an increased risk for lung cancer among non-smoking women (OR 2.2, CI 1.0-4.8) and low-dose smoking women (OR 4.8, CI 1.5-15.7). The protective effect of the variant XRCC3 241Met allele was strengthened when combined with the low-risk Glu185 allele of the NBS1 gene. Smokers (OR 0.38, CI 0.16-0.90) and women (OR 0.42, CI 0.21-0.85) with at least three low-risk alleles in these two HR genes showed a significantly decreased risk for lung cancer. Thus, in spite of a relatively small study population, this study, including a comparatively large number of never-smokers and women, presents several novel aspects on genetic susceptibility to lung cancer. Our results show that the genetic variation in XRCC1, XRCC3 and NBS1 influence lung cancer susceptibility among women, and that combinations of risk alleles in the two HR genes can enhance the effects.