Association between human leukocyte antigen polymorphism and human papillomavirus 16-positive vulval intraepithelial neoplasia in British women

Polymorphisms in human leukocyte antigen (HLA) genes have been implicated in the risk for developing human papillomavirus (HPV)-associated cervical neoplasia. By comparison with local cadaver controls typed for HLA class I (n = 946) and II (n = 144) antigens, HPV-16-positive high grade vulval intraepithelial neoplasia patients (n = 42) showed significantly different frequencies of HLA-A2 [odds ratio (OR), 2.1; confidence interval (CI), 1.4-3.9], HLA-B7 (OR, 2.6; CI, 1.4-4.7), HLA-DRB1*01(01/02/04) (OR, 0.1; CI, 0.03-0.5), HLA-DRB1*11 (OR, 3.3; CI, 1.4-7.1), HLA-DRB1*13 (OR, 0), HLA-DQB1*05 (OR, 0.2; CI, 0.05-0.6), and HLA-DQB1*03032 (OR, 4.6; CI, 1.5-14.0). With the exception of HLA-B7 and HLA-DRB1*11, these significant differences were also seen comparative to local HPV-16-positive cervical carcinoma patients (n = 114), suggesting a specific immunogenetic contribution that is independent of HPV-16 infection in high-grade vulval intraepithelial neoplasia. Such factors are important to the development of HPV vaccines for treatment of cervical and vulval neoplasia.     

HLA-DR4 is associated with a diminished risk of the development of chronic myeloid leukemia (CML). Chronic Leukemia Working Party of the European Blood and Marrow Transplant Registry.

CML is characterized by the chromosomal translocation t(9;22) (q34;q11) resulting in the chimeric bcr-abl oncogene that encodes P210 fusion proteins with novel amino acid sequences in the breakpoint region. If these peptides derived from P210 are presented by HLA molecules on the cell membrane of leukemic cells an immunological response may occur. Recent studies using synthetic peptides identical to the bcr-abl fusion region revealed that some peptides are capable of binding to the class I molecules HLA-A2,-A3,-A11 and -B8 and the class II molecules HLA-DR1, -DR2, -DR3, -DR4 and -DR11. Moreover T cell responses have been induced against bcr-abl-derived synthetic peptides bound to some of these HLA molecules. For HLA class I, we have previously shown that individuals expressing HLA-A3 and -B8 have a diminished risk of development of CML. To assess a similar protective effect of class II molecules we performed a large multi-center study. This study compared the frequencies of HLA-DR1, -DR2, -DR3, -DR4 and -DR11 of patients with CML from the database of the EBMT (n = 1462) with unaffected individuals from the registry of Bone Marrow Donors Worldwide (n = 500 596). Patients and controls were matched per country. This analysis yielded significantly lower odds ratios (ORs) of 0.86 (95% CI 0.75-0.98) for HLA-DR3 and of 0.80 (95% CI 0.71-0.89) for HLA-DR4. The OR was 0.91 (95% CI 0.80-1.04) for HLA-DR1, 1.05 (95% CI 0.94-1.18) for HLA-DR2 and 0.87 (95% CI 0.74-1.01) for HLA-DR11. To assess a possible effect of the linkage disequilibrium between HLA-B8 and HLA-DR3 we found that coexpression of HLA-B8 and HLA-DR3 gave an OR of 0.84 (95% CI 0.72-0.98), whereas HLA-DR3 positive/HLA-B8 negative individuals showed an OR of 1.02 (95% CI 0.84-1.24). This means that the protective effect of HLA-DR3 of the development of CML was probably caused by its linkage disequilibrium with HLA-B8. In contrast, as there is no linkage disequilibrium of HLA-DR4 with HLA-A3 or HLA-B8, the results indicate that HLA-DR4 expression itself is associated with a diminished incidence of CML possibly by the presentation of bcr-abl breakpoint peptides in these HLA molecules on the membrane of the leukemic cells.     

HLA-B*07 is a high risk allele for familial cervical cancer

Aim: The purpose of this study was to investigate 50 women from eight families with familial cervical cancer in Wufeng County, Hubei Province, China, a region with a high incidence of cervical cancer. Eighty-nine healthy women, of similar age, location and ethnicity, were selected as a control group. Methods: Blood samples were collected from both groups, and HLA-A, HLA-B, and HLA-DRB1 genotypes were profiled with the Multi-Analyte Profiling system (xMAP) (Luminex HLA-SSO) using a WAKFlow HLA typing kit. Results were analyzed with Luminex HLA typing software and showed good stability, reproducibility and specificity. Results: We found several high risk alleles in women with familial cervical cancer, that associated with the highest risk being HLA-B*07 (OR = 8.7, 95% CI = 1.8-41.1). Conclusions: HLA-B*07 is a high risk allele for cervical cancer, and has strong potential for use as a molecular biomarker.     

Human leukocyte antigens in Indian patients with chronic myeloid leukemia

In chronic myeloid leukemia (CML), experimental studies using synthetic peptides identical to the bcr-abl fusion region have revealed the capability of specific peptides to bind to human leukocyte antigen (HLA) class I molecules (HLA-A2, A3, A11, B8) and class II molecules (HLA-DR1, DR2, DR3, DR4 and DR11). Individuals expressing HLA-A3, B8 or DR4 have a diminished risk for the development of CML in Caucasian populations. A statistically significant increase in the frequency of Cw3 and Cw4 antigens in Caucasians and European CML patients has been reported. However, HLA associations in CML have not been reported in India. In lieu of the allelic diversity of HLA in the Indian population, the present study assessed the possibility of an association of HLA molecules in Indian patients with CML. HLA A, B, C and DRB1 antigen associations in 180 clinically diagnosed Indian CML patients (aged 17 - 54 years) were analysed and compared with age-matched (n = 100) healthy individuals from the same ethnic background. In the HLA class I antigen distribution, a significant decrease was observed in HLA-A11 (25.6% versus 39%; P = 0.027, odds ratio (OR) = 0.54, 95% confidence interval (CI) = 0.31 - 0.94) and HLA-Cw6 (7.8% versus 20%; P = 0.005, OR = 0.34, 95% CI = 0.15 - 0.74). Among the DRB1 alleles, HLA-DRB1*13 (7.8% versus 17%; P = 0.031, OR = 0.41, 95% CI = 0.18 - 0.93) was decreased in CML patients. However, the differences for HLA-A11 (P(c) = 0.351) and DRB1*13 (P(c) = 0.403) did not remain significant after the application of a correction factor for the P-value. These results suggest that the development of CML is apparently associated with HLA phenotypes specific to each population and indicate that expression of HLA-Cw6 may result in a protective effect on CML acquisition in the Indian population.     

Association between HLA-A/-B antigens and -DRB1 alleles and nasopharyngeal carcinoma in Tunisia

Using serologic and molecular methods, 45 nasopharyngeal carcinoma (NPC) patients were typed for HLA class I and class II and were compared to 100 unrelated normal Tunisians. Our results showed that the antigen frequency of HLA-B13 and allelic frequencies of DRB1*03, DRB1*15 were significantly higher in the NPC patients than in the control group (15.5 vs. 4; 26.4 vs. 11.5, and 14.4 vs. 6.5%, respectively) probably indicating a positive association with NPC. Moreover, we observed that HLA-A23 was absent in our NPC sample and was present in 18% of normal controls, and HLA-DRB1*11 was less frequent among the patients compared to the controls (5.5 vs. 14%) suggesting a protective effect of this association with NPC.     

HLA-A2 allelic microvariants in nasopharyngeal carcinoma

HLA-A2-positive nasopharyngeal carcinoma ( NPC; n = 38) and normal control (n = 51) populations were analysed by high-resolution oligotyping to identify A2 allelic microvariants. Within the control group, A*0207 was found to be the most common allele, accounting for 50% of the A2 frequency in normals. In contrast, this allele was found to be present in only 23% of NPC cases, suggesting a protective effect. Of these 9 NPC patients with A*0207, all were associated with B46, unlike in the control group, where it can be found associated with non-B46 antigens. Another allele, A*0201, which was thought to be protective against NPC was in fact present in 39.5% of NPC patients, more than twice the frequency in controls. These data confirm that A*0201 is not a protective allele for NPC, and other factors such as the A*0207, non-B46 haplotype are of greater importance.     

Study of human leukocyte antigen class I phenotypes in Moroccan patients with nasopharyngeal carcinoma

Previous reports demonstrated an association between the human leukocyte antigen (HLA) and risk for nasopharyngeal carcinoma (NPC) among the Chinese in Singapore, a population with a high incidence of this malignancy. In our study, we assess the association between HLA and NPC in Morocco, a median-prevalence area for this cancer, where NPC presents the particularity of also affecting young individuals. Using the standard microlympho-cytotoxicity test, we typed a total of 154 Moroccan NPC patients and 257 unrelated healthy controls for their HLA-A and B antigens. The results of these analyses show that the frequencies of HLA-A10, HLA-B13 and HLA-B18 were found to be higher in the NPC group than in the control group, whereas HLA-A9 was associated with a decreased risk. After correction for the number of specificities tested, these differences were statistically significant only for HLA-B18 (corrected p value [pc] < 0.023, relative risk [RR] = 4.14) and HLA-A9 (pc < 0.023, RR = 0.45). The comparison of the distribution of the HLA antigens in younger and older cohorts of patients shows that the incidence of HLA-A10 and HLA- B18 was higher in the older group, whereas the frequencies of HLA-A19 and HLA-B13 were significantly higher in younger patients compared with controls. The presence of both HLA-A19 and HLA-B13 phenotypes correlated with an increased risk of developing NPC among overall patients compared with controls. According to the sex distribution, increased frequency of HLA-B18 was found in male and female NPC patients compared with controls, whereas the frequency of HLA-A10 was higher only in male NPC patients compared with controls.     

Multiple low-frequency and rare HLA-B allelic variants are associated with reduced risk in 1,105 nasopharyngeal carcinoma patients in Hunan province,southern China

In our study, 1,105 cases of nasopharyngeal carcinoma (NPC) and 1,430 normal controls recruited from Hunan province, southern China were typed for human leukocyte antigen (HLA)-B locus by Sanger sequencing exons 2–4. Besides confirming the NPC association with HLA-B*46:01 allele, HLA-A*02:07-B*46:01 and HLA-A*33:03-B*58:01 haplotypes (all positive), and HLA-B*13 lineage (negative), all of which were relatively common, strong negative associations were observed for five low-frequency and rare alleles or lineages, including HLA-B*07, -B*27:04, -B*39, -B*51:02 and -B*55:02, with odds ratio (OR) ranging from 0.16 to 0.3 (all p_corrected < 0.05). These strong protective associations were independent of linkage disequilibrium (LD) between HLA-A and HLA-B loci. Further analysis indicated a single amino acid change from histidine to tyrosine at residue 171 is probably crucial for the mutant allele, HLA-B*51:02, to mediate resistance to NPC. A subset of NPC cases (n = 821) and normal controls (n = 1,035) were tested for antivirus capsid antigen immunoglobulin A (anti-VCA IgA), which differed drastically between the two groups [67.7% vs. 5.5%, OR (95% confidence interval) = 36 (26.55–48.81), p < 0.0001]. HLA-B allelic variation did not associate with seropositivity for anti-VCA IgA in either group. Results from our study show, more clearly than previously, the existence of a cluster of low-frequency and rare HLA-B variants conferring low, or very low risk to NPC, a phenomenon not observed in other ethnic groups. Our data shed new insights into genetic susceptibility to NPC in southern Chinese populations. Future independent studies are warranted to replicate the findings reported in our study.     

A protective association between the HLA-A2 antigen and nasopharyngeal carcinoma in us caucasians

Analyzing data from Caucasians participating in a multicentered population-based case-control study of nasopharyngeal carcinoma and HLA type in the US, we found persons with the A2 antigen to have a significantly lower risk than those with other antigens at the A locus [odds ratio (OR), 0.46; 95% confidence interval (C1), 0.21–0.96]. The protective association was stronger among presumptive homozygotes for A2. Similar results were obtained when cases were compared with US Caucasians typed either as part of the Collaborative Transplant Study, or by the 9th International Histocompatibility Workshop. These results are supported by a statistical summary of odds ratios for A2 from a number of previous studies in non-Chinese (summary OR, 0.69; 95% C1, 0.54–0.88). The odds ratio for patients with squamous-cell carcinomas was 0.56; among 7 patients with undifferentiated tumors the OR was 0.14. Results from in vitro studies of immune response to Epstein-Barr virus have found that the HLA-A2 antigen efficiently presents the EBV gene product LMP-2, which has been detected in NPC tumor cells. This offers a rationale for the observed protective association between the HLA-A2 antigen and nasopharyngeal carcinoma.     

CYP3A4 and CYP3A5 genotypes, haplotypes, and risk of prostate cancer.

Previous case-only studies have shown that men with the CYP3A4*1B promoter variant are at an increased risk of developing more aggressive forms of prostate cancer. However, no changes in CYP3A4 activity have been found in CYP3A4*1B carriers, suggesting that its association with disease may simply reflect linkage disequilibrium with another functional variant. CYP3A5 is located within 200 kb of CYP3A4, and a variant in CYP3A5 (*1/*3) correlates with function of the CYP3A5 enzyme. In this study, the potential effect of CYP3A4*1B and CYP3A5*1 on prostate cancer risk and aggressiveness were evaluated in a family-based case-control population. The CYP3A4*1B variant was positively associated with prostate cancer among Caucasians with more aggressive disease [odds ratio (OR), 1.91; 95% confidence interval (CI), 1.02-3.57; P=0.04], and inversely associated with risk among Caucasians with less aggressive disease (OR, 0.08; 95% CI, 0.01-0.49; P=0.006) and men with an age of diagnosis <63 (OR, 0.51; 95% CI, 0.26-1.00; P=0.05). The CYP3A5*1 variant was inversely associated with prostate cancer, especially among Caucasians with less aggressive disease (OR, 0.42; 95% CI, 0.22-0.78; P=0.006). As expected based on these genotype-level results, the CYP3A4*1B/CYP3A5*3 haplotype was positively associated with disease (OR, 2.91; 95% CI, 1.36-6.23; P=0.006), and the CYP3A4*1B/CYP3A5*1 haplotype was inversely associated with risk among Caucasians with less aggressive disease (OR, 0.07; 95% CI, 0.01-0.51; P=0.009). These findings suggest that the CYP3A4 and CYP3A5 variants, or other alleles on the haplotypes they help distinguish, are associated with prostate cancer risk and aggressiveness.     

Human leukocyte antigen (HLA) frequency among patients with nasopharyngeal carcinoma in Taiwan

In order to assess the association between human leukocyte antigens (HLA) and nasopharyngeal carcinoma (NPC), a total of 10 familial and 10 sporadic NPC patients and 171 unrelated healthy controls were studied. HLA typing was performed using commercial trays which defined 30 specificities of HLA-A, B and C loci and 10 specificities of HLA-D locus according to the method of Tiwari and Terasaki. HLA-A2, B16 and DR1 were found to be higher among patients with NPC than unrelated healthy controls with an odds ratio (OR) and a 95% confidence interval of 5.91 (2.1-16.6), 6.00 (2.0-18.0) and 6.89 (1.3-37.5), respectively. Further analysis showed that A2(+) B16(+) haplotype was significantly associated with a much higher risk of NPC (OR = 15.5) as compared with A2(-) B16(-) haplotype. No difference in frequency distributions of HLA-A, B, C and D antigens was observed between familial and sporadic NPC patients.     

HLA and MICA associations with head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) is a very aggressive tumour arising from the epithelial lining of the upper aerodigestive tract. The precise mechanisms involved in the pathogenesis of HNSCC have not been elucidated. Previous studies observed aberrant HLA expression patterns on HNSCC tumour cells and this study focused on the allelic polymorphism of HLA genes and the MHC class I chain related gene A (MICA) and HNSCC. We investigated whether associations with HLA and/or MIC alleles or haplotypes are involved in the pathogenesis of HNSCC and could explain the observed HLA expression patterns. Patients and controls were typed for HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 with sequence specific priming (SSP), supplemented with sequencing based typing (SBT). MICA allelic polymorphism was included and MICA allele assignment was based upon the combination of high resolution SBT of exons 2-4 in combination with repeat analysis and nucleotide polymorphism of exon 5. HLA-B *35 (p=0.014, OR=0.31) and HLA-B *40 (p=0.013, OR=2.9) were significantly associated in respectively the metastasized patients and the oral cavity patients. In addition, the HLA-B *40-DRB1 *13 haplotype (p=0.016, OR=4.1) was more often observed in the oral cavity patient group. The biological significance of the prevalence of specific HLA haplotypes in patients with oral cavity HNSCC and metastasizing HNSCC requires further investigation.     

Further evidence for an HLA-related recessive mutation in nasopharyngeal carcinoma among the Chinese

We typed 247 cases of nasopharyngeal carcinoma (NPC), a disease predominantly of the southern Chinese, and 274 controls from the Chao Shan region of China's Guangdong province for HLA A and B. Besides confirming the established associations with A2, A33, B46 and B58 (positive associations) and A11 (negative association), the results demonstrated a number of rarer alleles with strong negative association with NPC. Our data, combined with those from the previous studies in Southern Chinese, displayed the protective effects for A31 (odds ratio (OR)=0.0; 95% confidence interval (CI)=0-0.11), B13 (OR=0.50; 95% CI=0.35-0.69), B27 (OR=0.49; 95% CI=0.25-0.92), B39 (OR=0.18; 95% CI=0.06-0.48) and B55 (OR=0.32; 95% CI=0.14-0.68), the ORs comparing individuals with or without each allele. Other ethnic groups do not display such large HLA-associated variation in NPC risk. We show that a linked NPC gene with dominant mode of action could not generate such large protective effects. The results provide strong supporting evidence for the existence of a southern Chinese specific, recessive NPC gene closely linked to the HLA region as a major determinant of the Chinese risk for the disease.     

HLA-A,HLA-B,HLA-DRB1 Polymorphisms and Risk of Cervical Squamous Epithelial Cell Carcinoma: A Population Study in China

Cervical cancer is the second most common cancer in women. HLA class I and II alleles polymorphismshave been shown to be associated with cervical cancer risk, but results have varied among different populations.In this study, the HLA-A, -B, and –DRB1 alleles among 100 southern Chinese women with cervical squamouscell carcinoma (SCC) were compared to 254 controls. Our results showed that B*51:01:02 allele frequencywas significantly higher in patients with SCC than in healthy controls (P = 3.17x 10-5, Pc = 0.005, OR = 26.7).Statistical analysis also revealed a significantly decreased frequency of B*51:01:01 (P = 7.01x 10-4, Pc = 0.03, OR= 0.12) in patients with SCC when compared with healthy controls. These results indicate that HLA-B*51:01:02may confer susceptibility to SCC and HLA-B*51:01:01 may contribute to resistance to the development of SCCin Chinese women. None of the HLA-A-B or HLA-A-B-DRB1 haplotypes were significantly different in casesand controls after multiple testing corrections, indicating the individual allele associations to be independent ofthe identified haplotypes. These results support the hypothesis that some HLA-B alleles could be involved withsusceptibility for developing SCC.     

Helicobacter pylori and interleukin 1 genotyping: an opportunity to identify high-risk individuals for gastric carcinoma

BACKGROUND: Both Helicobacter pylori genotype and host genetic polymorphisms play a role in determining the clinical consequences of H. pylori infection. We investigated whether there are any combinations of bacterial and host genotypes that are particularly associated with the occurrence of gastric carcinoma. METHODS: Genotypic variations in virulence-associated genes of H. pylori vacA (s and m regions) and cagA were determined in 221 subjects with chronic gastritis and 222 patients with gastric carcinoma by polymerase chain reaction (PCR)-line probe assay. Polymorphisms in the human interleukin 1 beta (IL-1B) gene (IL-1B-511*C or IL-1B-511*T) and in the IL-1 receptor antagonist gene (IL-1RN intron 2 variable number of tandem repeats) were evaluated by PCR and single-strand conformation polymorphism analysis. All statistical tests were two-sided. RESULTS: Infection with vacAs1-, vacAm1-, and cagA-positive strains of H. pylori was associated with an increased risk for gastric carcinoma, with odds ratios (ORs) of 17 (95% confidence interval [CI] = 7.8 to 38), 6.7 (95% CI = 3.6 to 12), and 15 (95% CI = 7.4 to 29), respectively. IL-1B-511*T carriers (IL-1B-511*T/*T or IL-1B-511*T/*C) homozygous for the short allele of IL-1RN (IL-1RN*2/*2) had an increased gastric carcinoma risk (OR = 3.3, 95% CI = 1.3 to 8.2). For each combination of bacterial/host genotype, the odds of having gastric carcinoma were greatest in those with both bacterial and host high-risk genotypes: vacAs1/IL-1B-511*T carrier (OR = 87, 95% CI = 11 to 679), vacAm1/IL-1B-511*T carrier (OR = 7.4, 95% CI = 3.2 to 17), cagA-positive/IL-1B-511*T carrier (OR = 25, 95% CI = 8.2 to 77), vacAs1/IL-1RN*2/*2 (OR = 32, 95% CI = 7.8 to 134), vacAm1/IL-1RN*2/*2 (OR = 8.8, 95% CI = 2.2 to 35), and cagA-positive/IL-1RN*2/*2 (OR = 23, 95% CI = 7.0 to 72). CONCLUSION: Combined bacterial/host genotyping may provide an important tool in defining disease risk and targeting H. pylori eradication to high-risk individuals.     

Genetic susceptibility to nasopharyngeal carcinoma within the HLA-A locus in Taiwanese

NPC is an epithelial tumor that is highly prevalent among the southern Chinese. Numerous studies have indicated that specific HLA haplotypes and genes within the HLA complex are associated with NPC. As a first effort to localize the gene responsible for susceptibility, the HLA-A, -B, and -A2 subtypes were examined for their association to NPC. Consistent with previous reports, frequencies of HLA-A2 [OR = 2.50, pc = 0.020 (study population); OR = 3.73, pc = 0.0030 (> or =40 years old)] were significantly higher in patients with NPC than in healthy controls. Two-locus analysis indicated that A2(+)B46(+) individuals are at greater risk for NPC than A2(-)B46(-) individuals in both the population studied and the > or =40-year-old group. This, however, may be due to the close linkage of these 2 genes. Moreover, A2(+)B38(+) individuals were at higher risk than A2(-)B38(-) individuals in both the population studied and the > or =40-year-old group; A2 and B38 are not genetically linked. These findings suggest that B38 or B46 alone cannot confer a high risk of NPC but that, in conjunction with A2, B38 or B46 positivity greatly increases risk. None of 5 A2 subtypes identified from studied populations was significantly associated with NPC. Microsatellite marker D6S211, located 97 kb telomeric to HLA-A, was analyzed for its association with NPC. Allele 4 of D6S211 was significantly associated with NPC (OR = 3.97, pc = 0.0042). These results strongly support the hypothesis that genes associated with susceptibility to NPC in the HLA region are within the HLA-A locus.     

Alcohol consumption, alcohol dehydrogenase 3 polymorphism, and colorectal adenomas.

Alcohol is a probable risk factor with regard to colorectal neoplasm and is metabolized to the carcinogen acetaldehyde by the genetically polymorphic alcohol dehydrogenase 3 (ADH3) enzyme. We evaluated whether the association between alcohol and colorectal adenomas is modified by ADH3 polymorphism. We recruited 433 cases with adenomatous polyps and 436 polyp-free controls among Caucasians undergoing endoscopy between 1995 and 2000. Frequency and amount of habitual alcohol consumption were assessed by beverage type, using a validated self-administered food frequency questionnaire. All participants provided blood for genotyping of ADH3. Multivariate analyses adjusting for gender, age, and indication for endoscopy showed that alcohol increased the risk of colorectal adenomas among women [odds ratio (OR), 1.8; 95% confidence interval (CI), 1.0-3.2, >/=10 versus <1 drink/week]. Among men, the risk of adenomas was increased only for those consuming > 21 drinks/week (OR, 1.8; 95% CI, 0.9-3.8, compared with men drinking < 1 drink/week). Among subjects in the highest tertile of alcohol consumption, those with the ADH3*1/*1 genotype were at higher risk (OR, 1.8; 95% CI, 1.0-3.1) than those with other ADH3 genotypes (OR, 1.2; 95% CI, 0.7-1.9) when compared with those in the lowest tertile with ADH3*1/*2 or ADH3*2/*2 genotypes. In conclusion, our findings are consistent with results of other studies, suggesting that alcohol consumption elevates the risk of adenomatous colorectal polyps. ADH3 polymorphism may modify the association between alcohol consumption and colorectal adenomas.     

Major histocompatibility complex class II polymorphisms and risk of cervical cancer and human papillomavirus infection in Brazilian women.

Infection with high-risk human papillomavirus (HPV) is the major risk factor for the development of malignant lesions in the uterine cervix. Environmental, behavioral, and ill-defined genetic factors also have been implicated in the pathogenesis of this disease. Associations between human leukocyte antigens (HLAs) and cervical cancer, precursor lesions, and HPV infections have been reported in several populations. To verify whether HLA-DRB1, -DQA1, and -DQB1 diversity is related to cervical cancer in the Brazilian population, 161 cases and 257 controls were HLA typed. Variants of DQA1 and DQB1 promoter regions were also typed in 92 cases and 228 controls. Polymorphism in HLA genes and promoters was distinguished by PCR-based methods, and the magnitude of associations was determined by logistic regression analysis. DRB1*15 [confounder-adjusted odds ratio (OR), 2.24; 95% confidence interval (CI), 1.29-3.90], DRB1*1503 (OR, 2.52; 95% CI, 1.16-5.48), and haplotype DRB1*15-DQB1*0602 (OR, 2.04; 95% CI, 1.15-3.61) were positively associated with cervical cancer. When we considered only DR15 haplotypes that did not carry the DQB1*0602 allele, the risk attributed to DRB1*15 more than doubled. A negative association was found between DQB1*05 and cervical cancer (OR, 0.57; 95% CI, 0.35-0.92), and similar trends were observed for DQA1*0101/04, DRB1*0101, and DRB1*1302. HPV positivity among controls was associated with DRB1*1503 (OR, 4.60; 95% CI, 1.33-15.9), DRB1*0405 (OR, 6.21; 95% CI, 1.66-23.2), and DQB1*0602 (OR, 2.48; 95% CI, 1.06-5.80). We suggest that HLA class II polymorphisms are involved in genetic susceptibility to cervical cancer and HPV infection in a Brazilian population from an area with a high incidence of this neoplasia.     

中国南方汉族急性淋巴细胞白血病患者572例的HLA基因和单倍型分析

 目的　研究HLA-A、B、DRB1基因和单倍型与中国南方汉族急性淋巴细胞白血病（ALL）的疾病相关性。方法　应用最大似然性方法分别计算南方汉族ALL患者组572例和5645名南方汉族健康供者HLA-A、B、DRB1基因和单倍型频率,采用χ2检验方法比较其分布差异。结果　ALL组HLA-A33、B58和DRB1*17基因频率均低于对照组[HLA-A33（7.15 %比9.3 %,OR＝0.73,P＜0.05）、B58（5.93 %比8.75 %,OR＝0.64,P＜0.05）和DRB1*17（5.15%比6.30 %,OR＝0.82,P＜0.05）];A3、B51和DRB*12基因频率均高于对照组[A3（2.1 %比1.26 %,OR＝1.7,P＜0.05）,B51（7. 25 %比5.78 %,OR＝1.3,P＜0.05）和DRB*12（16.13 %比12.99 %,OR＝1.35,P＜0.05）];HLA-A33-B58-DRB1*17单倍型频率低于对照组（2.46 %比4.14 %,OR＝0.35,P＜0.05）,A2-B51- DRB1*12单倍型频率高于对照组（1.24 %比0.89 %,OR＝1.66,P＜0.05）。结论　携带有A33-B58-DRB1*17单倍型个体可能与降低ALL的发病风险有相关性,A3基因和A2-B51- DRB1*12可能与增加ALL发病风险有弱相关性。     

Association of interleukin-1 gene polymorphisms with gastric cancer: a meta-analysis

Previous studies on the association between interleukin-1 (IL-1) genetic polymorphisms and the risk of gastric cancer have produced conflicting results. The purpose of this study was to examine the association between IL-1 genotype and gastric cancer by systematically reviewing the risk of the original studies. Thirty-nine studies, which included 6,863 gastric cancer cases and 8,434 controls, met the inclusion criteria and were included in the meta-analysis. By pooling all the studies identified, the summary odds ratio (OR) of gastric cancer risk associated with IL-1B-511T, -31C, +3954T and IL-1RN*2 was 1.26 (95% confidence interval (CI): 1.03-1.55), 1.00 (95% CI: 0.82-1.22), 1.37 (95% CI: 0.94-2.00) and 1.20 (95% CI: 1.01-1.41), respectively. A stratified analysis showed that IL-1B-511T was associated with an increased risk of gastric cancer (intestinal type) (OR = 1.76, 95% CI: 1.12-2.57). Moreover, IL-1RN*2 was also associated with an increased risk of gastric cancer among Caucasians (OR = 1.30, 95% CI: 1.09-1.54). In conclusion, IL-1B-511 and IL-1RN genetic polymorphisms are associated with an increased risk of developing gastric cancer.