Further characterization of clinical and laboratory features in VEXAS syndrome: large-scale analysis of a multicentre case series of 116 French patients.

BACKGROUND: A new autoinflammatory syndrome related to somatic mutations of UBA1 was recently described and called VEXAS syndrome ('Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic syndrome'). OBJECTIVES: To describe clinical characteristics, laboratory findings and outcomes of VEXAS syndrome. METHODS: One hundred and sixteen patients with VEXAS syndrome were referred to a French multicentre registry between November 2020 and May 2021. The frequency and median of parameters and vital status, from diagnosis to the end of the follow-up, were recorded. RESULTS: The main clinical features of VEXAS syndrome were found to be skin lesions (83%), noninfectious fever (64%), weight loss (62%), lung involvement (50%), ocular symptoms (39%), relapsing chondritis (36%), venous thrombosis (35%), lymph nodes (34%) and arthralgia (27%). Haematological disease was present in 58 cases (50%): myelodysplastic syndrome (MDS; n = 58) and monoclonal gammopathy of unknown significance (n = 12; all patients with MGUS also have a MDS). UBA1 mutations included p.M41T (45%), p.M41V (30%), p.M41L (18%) and splice mutations (7%). After a median follow-up of 3 years, 18 patients died (15·5%; nine of infection and three due to MDS progression). Unsupervised analysis identified three clusters: cluster 1 (47%; mild-to-moderate disease); cluster 2 (16%; underlying MDS and higher mortality rates); and cluster 3 (37%; constitutional manifestations, higher C-reactive protein levels and less frequent chondritis). The 5-year probability of survival was 84·2% in cluster 1, 50·5% in cluster 2 and 89·6% in cluster 3. The UBA1 p.Met41Leu mutation was associated with a better prognosis. CONCLUSIONS: VEXAS syndrome has a large spectrum of organ manifestations and shows different clinical and prognostic profiles. It also raises a potential impact of the identified UBA1 mutation.

[The diagnostic performance of 2020 Chinese Ultrasound Thyroid Imaging Reporting and Data System in thyroid nodules].

Objective: To evaluate the diagnostic performance of the Chinese Ultrasound Thyroid Imaging Reporting and Data System (C-TIRADS) in thyroid nodules,and to compare it with the TIRADS proposed by Kwak et al. (K-TIRADS) and the TIRADS proposed by the American College of Radiology (ACR-TIRADS). Methods: The data of 1 750 patients with 2 029 thyroid nodules in the Department of Thyroid Surgery, the Affiliated Hospital of Jining Medical University from January 2018 to November 2020 was retrospectively collected. Among them, there were 328 males and 1 422 females,aged from 6 to 86 with an average of (47±12) years. The nodules were divided into≤1.0 cm group(n=997) and>1.0 cm group(n=1 032)based on the size of the nodules. The stratification for malignant risk and the determination of benign or malignancy of the nodules was evaluated using the C-TIRADS, K-TIRADS and ACR-TIRADS, respectively. The receiver operating characteristic (ROC)curve analysis was performed to compare the diagnostic performance of the aforementioned three kinds of TIRADS using pathological results as the referent standard. Results: The optimal diagnosis points in the determination of malignant nodules of C-TIRADS, K-TIRADS and ACR-TIRADS in the two groups were 4A, 4b and 4 respectively according to ROC curve analysis. For the diagnosis of the malignant nodules, the C-TIRADS achieved with an AUC value of 0.772 and 0.892 in the ≤1.0 cm group and>1.0 cm group, respectively, which was significantly higher than K-TIRADS (AUC= 0.762 and 0.869, respectively) and ACR-TIRADS (AUC= 0.735 and 0.832, respectively) (P<0.05). The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of C-TIRADS were 94.99%, 59.41%, 86.46%, 88.13%, 78.89% (≤1.0 cm group)and 88.34%, 90.05%, 89.34%, 86.33%, 91.57%(>1.0 cm group), respectively. C-TIRADS had the highest sensitivity, accuracy, and negative predictive value in the determination of malignant nodules in both groups compared to the other two kinds of TIRADS. Conclusions: The three kinds of TIRADS all have high diagnostic performance for the determination of the malignant nodules, and the C-TIRADS has the best overall efficacy, which can effectively assist clinicians for medical decision, and is worth to be popularized and applied in the clinical setting.

[Amplitude of low-frequency fluctuations of resting-state functional MRI in colorectal cancer patients with depression].

Objective: To investigate the alterations of the cerebral resting-state spontaneous neural activity in colorectal cancer patients with depressive symptoms. Methods: Thirty-three colorectal cancer patients (patient group) with depression and 43 healthy subjects (control group) underwent the resting state functional magnetic resonance imaging (rs-fMRI). The amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF) were calculated. Two independent samples t test were used to compare the ALFF and fALFF values between two groups by DPABI software, and then correlation analysis was performed between ALFF and fALFF with statistical significance and Patient Health Questionnaire (PHQ-9) scores and Generalized Anxiety Disorder (GAD-7) scores. Results: Compared with the control group, the patient group showed significantly lower ALFF and fALFF values in the bilateral precuneus, calcarine gyrus, lingual gyrus, left cuneus, superior, middle, inferior occipital gyrus and right fusiform gyrus (t=-5.730, P<0.05; t=-4.872, P<0.05). There were no significant correlations between the ALFF and fALFF values in these regions and PHQ-9 or GAD-7 scores (P>0.05). Conclusion: Spontaneous decrease of neural activity in occipital and parietal lobes exists in colorectal cancer patients with depression at resting-sate, which may be a potential neurobiological marker.

[Two procedures for ridge preservation of molar extraction sites affected by severe bone defect due to advanced periodontitis].

OBJECTIVE: To evaluate and to compare dimensional alterations of hard and soft tissues in molar extraction sites with irregular deficiency of bone plates due to advanced periodontitis receiving two different procedures, namely the flapped and flapless techniques with Bio-Gide membrane covering the Bio-Oss material for ridge preservation. METHODS: Twenty-three patients with 24 infected-molar extraction sites received ridge preservation procedure, the first consecutive 12 sites belonged to the flap group (a full thickness mucoperiosteal flap and primary soft tissue closure) and the following 12 sites belonged to the flapless group (minimal flap with a collagen sponge and a secondary soft tissue closure). Width of keratinized tissue was evaluated before tooth extraction and after 6-month healing. Parallel periapical radiographs were taken immediately and 6 months after extraction to evaluate vertical bone changes. The width of the ridge was measured in the center of the ridge at the time of tooth extraction and after 6 months at implant placement. RESULTS: After 6 months, width of keratinized tissue decreased (1.6±1.5) mm in the flap group (P=0.004) when compared with (0.3±1.6) mm in the flapless group (P>0.05). Both groups showed increases in ridge height from the central aspect, (5.53±4.20) mm for flap group and (7.70±4.35) mm for flapless group. These differences between the groups were not statistically significant (P=0.226). The ridge widths were (9.5±2.2) mm for flap group and (9.3±1.0) mm for flapless group at the time of implant insertion, and no statistical significance was observed between the flap and flapless groups. CONCLUSION: The study points out that both ridge preservation techniques were effective in increasing ridge height and minimizing ridge resorption after tooth extraction, and the ridge width allowed the placement of implants 6 months after ridge preservation. The flapless technique gave positive outcome in terms of the keratinized gingival width than that of the flap technique.

Significant variation between SNP-based HLA imputations in diverse populations: the last mile is the hardest.

Four single nucleotide polymorphism (SNP)-based human leukocyte antigen (HLA) imputation methods (e-HLA, HIBAG, HLA*IMP:02 and MAGPrediction) were trained using 1000 Genomes SNP and HLA genotypes and assessed for their ability to accurately impute molecular HLA-A, -B, -C and -DRB1 genotypes in the Human Genome Diversity Project cell panel. Imputation concordance was high (>89%) across all methods for both HLA-A and HLA-C, but HLA-B and HLA-DRB1 proved generally difficult to impute. Overall, <27.8% of subjects were correctly imputed for all HLA loci by any method. Concordance across all loci was not enhanced via the application of confidence thresholds; reliance on confidence scores across methods only led to noticeable improvement (+3.2%) for HLA-DRB1. As the HLA complex is highly relevant to the study of human health and disease, a standardized assessment of SNP-based HLA imputation methods is crucial for advancing genomic research. Considerable room remains for the improvement of HLA-B and especially HLA-DRB1 imputation methods, and no imputation method is as accurate as molecular genotyping. The application of large, ancestrally diverse HLA and SNP reference data sets and multiple imputation methods has the potential to make SNP-based HLA imputation methods a tractable option for determining HLA genotypes.

[Antimicrobial susceptibility and genotyping of Mycobacterium intracellulare].

Objective: To investigate the antimicrobial susceptibility and genotyping of Mycobacterium intracellulare. Methods: A total of 150 M. intracellulare isolates were collected. The susceptibility against 15 antimicrobial agents widely used for treatment of non-tuberculosis mycobacteria (NTM) infections, was tested by broth microdilution assay. Variable number of tandem repeats (VNTR) assay was also performed using the 16-loci genotyping method. Results: The drug susceptibility test revealed that clarithromycin (97.3%, 146/150), moxifloxacin (94.0%, 141/150) and amikacin (90.0%, 135/150) had the best antimicrobial activities in vitro against the M. intracellulare isolates. Secondly, 75.3%(113/150), 64.0%(96/150), 52.7%(79/150) and 8.7%(13/150) of the strains were susceptible to rifampicin, linezolid, capreomycin, and ethambutol, respectively. The MIC(50) and MIC(90) values of the 3 injectable anti-tuberculosis drugs were as follows: amikacin 4 mg/L and 16 mg/L, streptomycin 4 mg/L and 16 mg/L, capreomycin 8 mg/L and 16 mg/L. The MIC(50) and MIC(90) values of the 5 different fluoroquinolones were 0.5 mg/L and 2 mg/L for moxifloxacin , 1 mg/L and 8 mg/L for ciprofloxacin, 1 mg/L and 8ug/ml for levofloxacin, 2 mg/L and 16 mg/L for antoflolxacin, 2 mg/L and 16 mg/L for ofloxacin. The Hunter-Gaston Discriminatory Index (HGDI) value for the 16-loci VNTR typing of M. intracellulare isolates was 0.994. VNTR differentiated the 150 isolates into 21 clusters and acquired a total of 121 unique patterns. Drug resistance profile was not independently associated with cluster strains. Conclusions: Clarithromycin, moxifloxacin and amikacin had the best antimicrobial activities in vitro against M. intracellulare isolates. The 16-loci VNTR typing revealed a highly discriminatory power and drug resistance profile was not independently associated with cluster strains.

[Correlation between ultrasonographic optic nerve sheath diameter and intracranial pressure].

Objective: To evaluate the association of the ultrasonographic optic nerve sheath diameter (ONSD) and intracranial pressure (ICP), and the feasibility of ultrasonographic ONSD in predicting high ICP. Methods: A prospective study. The outpatients who planned to measure ICP by lumbar puncture in Department of Neurology, Xuanwu Hospital, Capital Medical University were selected from January 2011 to May 2012. All the retrobulbar ONSD measurement with B-scan ultrasound was performed just before lumbar puncture. When high ICP was defined as ICP more than 200 mmH2O(1 mmH2O=0.009 8 kPa), the participants were divided into the high ICP group and the normal ICP group. The Pearson correlation coefficient analysis was used to analyze the correlation between ICP and postbulbar ONSD measurements. The difference in ONSD was compared between the high ICP and normal ICP groups with the t test. The receiver operating characteristic (ROC) curve was used to calculate the cutoff value of mean ONSD and evaluate the sensitivity and specificity of the method. Results: A total of 130 participants were involved in this study. There were 71 males and 59 females, aged (38±14) years.The mean ICP was (209.84±79.99) mmH2O. The mean ONSD was (5.68±0.78) mm in the right eyes, (5.78±0.78) mm in the left eyes, and (5.73±0.71) mm in both eyes. The ICP had a significant correlation with ONSD in the right eyes (r=0.54, P<0.001), ONSD in the left eyes (r=0.56, P<0.001) and ONSD in both eyes (r=0.60, P<0.001), but no correlation with age (r=-0.14, P=0.114) and gender (r=0.20, P=0.817). The ONSD in the high ICP group (n=65) was (6.11±0.66) mm, (6.22±0.56) mm and (6.17±0.50) mm in the right eyes, left eyes, and both eyes, respectively. Compared with the ONSD in the normal ICP group (n=65), which was (5.26±0.64) mm in the right eyes, (5.34±0.72) mm in the left eyes and (5.30±0.62) mm in both eyes, there was a significantly enlarged ONSD in the high ICP group (t=-7.507, -7.778, -8.779, all P<0.001). The ROC analysis showed the ONSD of 5.6 mm was the best cutoff value with a sensitivity of 86% and a specificity of 71% for identifying high ICP. Conclusions: There is a significantly positive correlation between ICP and postbulbar ONSD measured by ultrasound. This non-invasive method may be an alternative approach to predicting the ICP value of patients whose ICP measurement via lumbar puncture is at high risk. However, it can not replace the direct ICP measurement with the invasive method. (Chin J Ophthalmol, 2018, 54: 683-687).

[Evaluation of a high-intensity fluorescent fluorophage method for diagnosis of drug-resistance in tuberculosis].

Objective: To evaluate the high-intensity green fluorescent protein fluorophage Φ(2)GFP10 method for drug susceptibility testing of tuberculosis for isoniazid(INH), rifampin(RIF), and streptomycin(SM). Methods: A total of 128 clinical M. tuberculosis strains were isolated from patients with suspected drug-resistant tuberculosis visiting Beijing Chest Hospital (Beijing, China) from April to June 2014.All of the isolates were tested by the phage assay, while conventional drug susceptibility tests were performing on Lwenstein-Jensen culture medium as reference. Results: The sensitivities of Φ(2)GFP10 assay for INH, RIF, and SM resistance detection were 100.0%, 98.1%(53/54), and 92.6%(50/54), respectively, while their specificities were 84.8%(56/66), 91.9%(68/74), and 91.9%(68/74), respectively. The agreement between the phage assay and the conventional assay for detecting INH, RIF, and SM resistance was 0.92, 0.95 and 0.92, respectively. The Φ(2) GFP10-phage assay could be done within 2 days for RIF and SM, and 3 days for INH. Conclusions: The Φ(2)GFP10-phage method for drug susceptibility test is very sensitive and specific. The method has the potential to be a valuable, rapid and economical screening method for detecting drug-resistant tuberculosis.

[Dental implantation and soft tissue augmentation after ridge preservation in a molar site: a case report].

For ideal implant rehabilitation, an adequate bone volume, optical implant position, and stable and healthy soft tissue are required. The reduction of alveolar bone and changes in its morphology subsequent to tooth extraction will result in insufficient amount of bone and adversely affect the ability to optimally place dental implants in edentulous sites. Preservation of alveolar bone volume through ridge preservation has been demonstrated to reduce the vertical and horizontal contraction of the alveolar bone crest after tooth extraction and reduce the need for additional bone augmentation procedures during implant placement. In this case, a patient presented with a mandible molar of severe periodontal disease, the tooth was removed as atraumatically as possible and the graft material of Bio-Oss was loosely placed in the alveolar socket without condensation and covered with Bio-Gide to reconstruct the defects of the alveolar ridge. Six months later, there were sufficient height and width of the alveolar ridge for the dental implant, avoiding the need of additional bone augmentation and reducing the complexity and unpredictability of the implant surgery. Soft tissue defects, such as gingival and connective tissue, played crucial roles in long-term implant success. Peri-implant plastic surgery facilitated development of healthy peri-implant structure able to withstand occlusal forces and mucogingival stress. Six months after the implant surgery, the keratinized gingiva was absent in the buccal of the implant and the vestibular groove was a little shallow. The free gingival graft technique was used to solve the vestibulum oris groove supersulcus and the absence of keratinized gingiva around the implant. The deepening of vestibular groove and broadening of keratinized gingiva were conducive to the long-term health and stability of the tissue surrounding the implant. Implant installation and prosthetic restoration showed favorable outcome after six months.

Effects of bedding material composition in deep litter systems on bedding characteristics and growth performance of limousin calves.

The objective of this study was to evaluate the effects of different litter mixture compositions on bedding system temperature, pH and volatile fatty acid and ammonia-N (NH3-N) content, and the serum physico-chemical parameters and growth indices of calves. Thirty-two Limousin calves (280±20 kg) were randomly assigned to four groups (n = 8 for each group) according to the bedding system used: i) control with soil only (CTR); ii) mixture with 50% paddy hulls (PH), 30% saw dusts (SD), 10% peat moss (PM) and 10% corn cobs (CC) (TRT1); iii) mixture with 15% PH, 15% SD, 10% PM, 40% CC, and 20% corn stover (CS) (TRT2); iv) mixture with 30% PH, 10% PM, 40% CC, and 20% CS (TRT3). The litter material combinations of different treatments were based on the cost of bedding system materials in China. The cost of four treatments from low to high: Control

Phase II study of sorafenib in combination with cisplatin and 5-fluorouracil to treat recurrent or metastatic nasopharyngeal carcinoma.

BACKGROUND: We aimed to investigate the efficacy and tolerability of sorafenib combined with cisplatin and 5-fluorouracil (5-FU) in patients with recurrent or metastatic nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: It was a Simon two-stage designed trial. Chemotherapy-naive patients with recurrent or metastatic disease were enrolled. The regimen was sorafenib 400 mg orally b.i.d., cisplatin 80 mg/m(2) i.v. day 1, and 5-FU 1000 mg/m(2)/day CIV for 4 days, repeated every 21 days. After a maximum of six cycles of chemotherapy, patients received maintenance of sorafenib. RESULTS: In total, 54 patients were enrolled. The objective response rate reached 77.8%, including 1 complete response and 41 partial responses. The median progression-free survival was 7.2 months (95% CI 6.8-8.4 months), and the median overall survival was 11.8 months (95% CI 10.6-18.7 months). Major toxic effects included hand-foot skin reaction, myelosuppression, and gastrointestinal (GI) reaction. The incidence of hemorrhage was 22.2%, and one patient with liver metastases died of GI bleeding. Contrast-enhanced ultrasonography was carried out in a subset of patients with liver metastases. CONCLUSION: Combination of sorafenib, cisplatin (80 mg/m(2)) and 5-FU (3000 mg/m(2)) was tolerable and feasible in recurrent or metastatic NPC. Further randomized trials to compare sorafenib plus cisplatin and 5-FU with standard dose of cisplatin plus 5-FU in NPC are warranted.

Somatic mutations in the HLA genes of patients with hematological malignancy.

Somatic mutations and genomic alterations are frequent events in the clonal evolution of hematologic malignancies. Recent studies have reported copy neutral loss of heterozygosity (LOH) for the mismatched human leukocyte antigen (HLA) haplotype in patients relapsed after haploidentical hematopoietic cell transplantation (HCT) for a hematologic malignancy. Herein, we report 15 cases of somatic mutations in the HLA genes of patients with a variety of hematologic diseases, including acute myelogenous leukemia, acute lymphocytic leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia, myelodysplastic syndrome, and non-Hodgkin's lymphoma, encountered at our institute over the past decade. While two of the cases were identified in patient relapse specimens collected post-HCT, 13 cases were found in peripheral blood specimens submitted for HLA typing prior to transplantation. Ten patients exhibited acquired LOH for all or part of one HLA haplotype. Five other cases involved somatic mutations in the nucleotide sequences of common HLA-A or HLA-B alleles. Since they are not systematically evaluated prior to HCT, acquired mutations in HLA genes are likely under reported. Beyond the implications for accurate HLA typing and donor selection, alternations that result in the loss of HLA expression may allow escape from immune surveillance and adversely impact transplant outcome.

Association of SPINK5 gene polymorphisms with atopic dermatitis in Northeast China.

BACKGROUND: Defect in the SPINK5 gene is known to be implicated in Netherton syndrome (NS), and has been suggested to be a locus predisposing to atopy in general. Coding polymorphisms in SPINK5 exons 13, 14 and 26 have been reported to be associated with atopic dermatitis (AD), asthma and high level of IgE. OBJECTIVES: To examine whether the SPINK5 gene polymorphisms are associated with AD in Northeast China, and to assess how variants influence selected phenotypic traits. METHODS: A case-control study was conducted on four non-synonymous polymorphisms in the coding region of SPINK5 in AD and controls. The SPINK5 gene polymorphisms were analyzed using the PCR and RFLP methods. RESULTS: For the four non-synonymous SNPs, A1103G(Asn368Ser), G1156A(Asp386Asn), G1258A(Glu420Lys), G2475T(Glu825Asp) in SPINK5, the allelic frequencies in the AD cohort were 0.55 for 1103G, 0.57 for 1156A, 0.54for 1258A, 0.62 for 2475T, consistent with those already published in the original British and Japanese cohorts. The T allele of SNP 2475G > T was found to be significantly associated with AD. There were significant differences in genotype frequencies for G1258A(Glu420Lys) and G2475T(Glu825Asp) but not for A1103G(Asn368Ser) and G1156A(Asp386Asn). Genotypes GA(420Glu/Lys), TT (2475Asp/Asp) and GT(2475Glu/Asp) were significantly more frequent in AD. However, the SPINK5 gene polymorphisms was found not to be associated with AD in regard to either serum IgE levels, concurrent allergic asthma or early onset of AD. CONCLUSIONS: Our study confirms the association between SPINK5 and AD.

[Analysis of genetic characteristics in two Chinese children of type â ¡ Waardenburg syndrome].

Objective: To screen and analyze the mutations of MITF gene in two children of type Ⅱ Waardenburg syndrome (WS2) from different families in Yunnan,China,and to explore the possible molecular pathogenesis. Methods: With informed consent, medical history collection, physical examinations, audiological evaluation, and high resolution computer tomography (HRCT) scan of temporal bone were performed on the two WS2 probands and their family members. Genomic DNA was extracted from peripheral blood of all individuals. The coding regions including all exons, part of introns and promoters of MITF, PAX3, SOX10, SNAI2, END3, ENDRB, and KITLG genes were sequenced by high-throughput sequencing. According to the results of high-throughput sequencing, pathogenic mutations detected in the probands and their parents were verified by Sanger sequencing. Results: The proband 1 carried c.641_643delGAA mutation in the 7th exon of MITF gene, which was a frame-shift mutation resulting in an amino acid change of p.214delR. It was a de novo mutation as the parents of proband 1 showed no variation on this site. The proband 2 carried heterozygous loss of the large fragment ranging from exon 1 to exon 9 of MITF gene, which defected the function of MITF protein. Conclusion: Genetic examinations provide important evidence for diagnosis of Waardenburg syndrome. Heterozygous mutation c.641_643delGAA and heterozygous loss of the large fragment ranging from exon 1 to exon 9 of MITF gene might be the molecular pathogenesis of the two WS2 probands in this study.

Abnormal expression of Rap2A as a prognostic marker for human breast cancer.

OBJECTIVE: The aim of this study was to explore the expression of GTPase protein Ras-related protein Rap-2a (Rap2A) in breast cancer (BC). Furthermore, the associations of Rap2A with clinicopathological parameters of BC patients were investigated. PATIENTS AND METHODS: quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to examine Rap2A expression in BC tissues and cells. The association between Rap2A expression and clinicopathological characteristics was analyzed by Chi-square test. Low expression of Rap2A in BC cells was conducted by transfection of small interfering RNA (siRNA). Subsequently, colony formation assay and transwell assay were used to detect the proliferation and invasion abilities of BC cells, respectively. RESULTS: Rap2A was highly expressed in both BC tissues and cells (p<0.05). Further analysis showed that tumor size, clinical stage, and distant metastasis were correlated with Rap2A expression (p<0.05). Besides, inhibition of Rap2A significantly decreased the proliferation and invasion abilities of BC cells (p<0.05). CONCLUSIONS: Rap2A acted as a promotor in the development of BC. Our findings suggested that Rap2A might be a new potential therapeutic target marker for BC treatment.

Genetic variation in CXCL12 and risk of cervical carcinoma: a population-based case-control study.

CXCL12 provides a chemotactic signal-directing leucocyte migration and regulates metastatic behaviour of tumour cells. We conducted a population-based case-control study to test the hypothesis that common genetic variation in CXCL12 individual single nucleotide polymorphism (SNP) alleles and haplotypes] is associated with the risk of cervical carcinoma. Cases (n = 917) were residents of western Washington State diagnosed with invasive squamous cell cervical carcinoma (SCC), invasive adenocarcinoma or adenosquamous carcinoma, or adenocarcinoma in situ of the cervix. Control participants (n = 849) were identified from the source population by random digit telephone dialling and frequency matched to cases on county and age. Nine CXCL12 tagSNPs chosen from the SeattleSNPs database were genotyped. The minor allele of intronic SNP rs266085 was inversely associated with cervical cancer under a recessive genetic effects model (OR = 0.74, 95% CI: 0.56-0.98). Among the ten common haplotypes inferred from the nine tagSNPs, one haplotype defined by minor alleles at 5'-flanking SNP rs17885289 and rs266085, and common alleles at the other seven SNPs occurred among 7.8% of cases and 10.6% of controls (dominant model OR = 0.72, 95% CI: 0.56-0.93; recessive model OR = 0.35, 95% CI: 0.12-0.97; and log-additive model OR = 0.72, 95% CI: 0.57-0.90). A stepwise procedure identified rs17885289, rs266085 and 3'-untranslated region (UTR) SNP rs266093 as the most parsimonious subset of SNPs necessary to define the haplotype inversely associated with cervical cancer risk in our study. A 3'-UTR SNP, rs1801157, previously found to be related to HIV pathogenesis, was not associated with cervical cancer risk. Further population-based studies are warranted to confirm these associations between genetic variation in CXCL12 and cervical cancer risk.