摘要
Polymorphisms of hormone receptor genes have been linked to modifications in reproductive factors and to an increased risk of breast cancer (BC). In the present study, we have determined the allelic and genotypic frequencies of the ERα-397 PvuII C/T, ERα-351 XbaI A/G and PGR PROGINS polymorphisms and investigated their relationship with mammographic density, body mass index (BMI) and other risk factors for BC. A consecutive and unselected sample of 750 Brazilian BC-unaffected women enrolled in a mammography screening program was recruited. The distribution of PGR PROGINS genotypic frequencies was 72.5, 25.5 and 2.0% for A1A1, A1A2 and A2A2, respectively, which was equivalent to that encountered in other studies with healthy women. The distribution of ERα genotypes was: ERα-397 PvuII C/T: 32.3% TT, 47.5% TC, and 20.2% CC; ERα-351 XbaI A/G: 46.3% AA, 41.7% AG and 12.0% GG. ERα haplotypes were 53.5% PX, 14.3% Px, 0.3% pX, and 32.0% px. These were significantly different from most previously published reports worldwide (P < 0.05). Overall, the PGR PROGINS genotypes A2A2 and A1A2 were associated with fatty and moderately fatty breast tissue. The same genotypes were also associated with a high BMI in postmenopausal women. In addition, the ERα-351 XbaI GG genotype was associated with menarche ≥12 years (P = 0.02). ERα and PGR polymorphisms have a phenotypic effect and may play an important role in BC risk determination. Finally, if confirmed in BC patients, these associations could have important implications for mammographic screening and strategies and may be helpful to identify women at higher risk for the disease.
Subject(s)
Adult , Aged , Female , Humans , Middle Aged , Breast Neoplasms/genetics , Deoxyribonucleases, Type II Site-Specific/genetics , Estrogen Receptor alpha/genetics , Genetic Predisposition to Disease , Polymorphism, Genetic/genetics , Receptors, Progesterone/genetics , Body Mass Index , Brazil , Breast Neoplasms/diagnosis , Gene Frequency , Genotype , Mammary Glands, Human/abnormalities , Prevalence , Risk Factors摘要
Several studies have identified the single nucleotide polymorphism STK15 F31I as a low-penetrance risk allele for breast cancer, but its prevalence and risk association in the Brazilian population have not been determined. The goal of this study was to identify the frequency of this polymorphism in the Brazilian setting. Considering the high degree of admixture of our population, it is of fundamental importance to validate the results already reported in the literature and also to verify the relationship between this variant and breast cancer risk. A total of 750 women without breast cancer were genotyped using the TaqMan PCR assay for STK15 F31I polymorphism. Clinical information was obtained from review of the medical records and mammographic density from the images obtained using the BI-RADS System. The estimated risk of developing cancer was calculated according to the Gail model. The genotypic frequencies observed in this study were 4.5, 38.7, and 56.6 percent, respectively, for the STK15 F31I AA, AT and TT genotypes. The AT and AA genotypes were encountered significantly more often in premenopausal women with moderately dense, dense and heterogeneously dense breast tissue (P = 0.023). In addition, the presence of the TT genotype was significantly associated with age at menarche ≥12 years (P = 0.023). High mammographic density, associated with increased breast cancer risk, was encountered more frequently in premenopausal women with the risk genotypes STK15 F31I AA and AT. The genotypic frequencies observed in our Brazilian sample were similar to those described in other predominantly European populations.
Subject(s)
Adult , Aged , Female , Humans , Middle Aged , Breast Neoplasms/genetics , Mammography , Polymorphism, Single Nucleotide/genetics , Protein Serine-Threonine Kinases/genetics , Breast Neoplasms/enzymology , Breast Neoplasms , Gene Frequency , Genetic Predisposition to Disease , Genotype , Polymerase Chain Reaction , Prevalence , Risk Factors摘要
OBJECTIVE: To evaluate the immunogenicity of the Hepatitis B and Haemophilus influenzae type b components and the overall safety and reactogenicity of the DTPw-HBV/Hib vaccine when given as primary vaccination to Indian infants. DESIGN AND METHODS: At 3 centers in India, 225 healthy infants (who had received HBV at birth) received three doses of DTPw-HBV/Hib vaccine at 6, 10 and 14 weeks of age. Serum anti-HBs and anti-PRP antibody levels were measured prior to vaccination and one month post dose 3. Solicited local and general symptoms reported during the 4-day follow-up period and unsolicited adverse event reported during the 30-day follow-up period after each dose were recorded. Serious adverse events were recorded throughout the study. RESULTS: A total of 219 subjects completed the study. 2.7% and 11.5% of all administered doses led to redness and swelling >20 mm, respectively; only 3.6% of doses were followed by severe pain (cried when limb was moved, spontaneously painful) within 4 days after vaccination. Fever exceeding 39.5C was recorded following only one dose in one subject. The percentage of doses followed by severe solicited general symptoms (symptoms that prevented normal activity) did not exceed 0.8%. Two SAEs were reported, neither of which were considered as related to vaccination. One month post-dose 3, all subjects had seroprotective antiPRP antibody concentrations (> or =0.15 microgram/mL) and 98.6% had concentrations > or =1 microgram/mL; 99% were seropositive for antiHBs (concentrations > or = 3 mIU/mL) and 99% were seroprotected (concentrations > or = 10 mIU/mL). CONCLUSION: The combination DTPw-HBV/Hib vaccine is immunogenic (for the antigens tested), safe and well tolerated in Indian infants.
Subject(s)
Antibodies, Bacterial/blood , Antibodies, Viral/blood , Bacterial Capsules , Diphtheria-Tetanus-acellular Pertussis Vaccines/administration & dosage , Female , Haemophilus Vaccines/administration & dosage , Hepatitis B Vaccines/administration & dosage , Humans , Immunization Schedule , Infant , Male , Polysaccharides, Bacterial/administration & dosage , Vaccines, Combined/administration & dosage摘要
OBJECTIVE: To evaluate the safety and reactogenicity of a reduced-antigen-content combined Diphtheria Tetanus Acellular Pertussis (dTpa) vaccine in Indian preschool children. METHODS: GlaxoSmithKline Biologicals combination dTpa vaccine was administered as a single booster dose to 347 children aged 46 years in seven centers across India. All children were subsequently followed up for two weeks for safety and reactogenicity assessment. RESULTS: A total of 345 subjects completed the study and two subjects were lost to follow-up. One serious adverse event (head injury) unrelated to vaccination was reported. Otherwise, all subjects were in good health throughout the study period. Three subjects (0.9%) reported transient general symptoms (such as irritability and drowsiness), which prevented normal activity. Pain at injection site, swelling and redness was reported in 31.1%, 18.2% and 8.9% subjects respectively. Five subjects (1.4%) reported severe pain preventing normal movement. This resolved within 48 hours in all cases. There were no other severe local reactions including large injection site reactions. CONCLUSION: The reduced antigen content combined dTpa vaccine is safe and well tolerated in Indian pre-school children.
Subject(s)
Child , Child, Preschool , Diphtheria-Tetanus-acellular Pertussis Vaccines/administration & dosage , Female , Guideline Adherence , Humans , Immunization/adverse effects , India , Male , Patient Compliance , Prospective Studies , Whooping Cough/prevention & control摘要
An open, randomized study evaluated the immune response and safety of two different regimens of diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b (DTPa-HBV-IPV-Hib) immunization in infants primed at birth with hepatitis B vaccine. One-half of the 150 healthy, full-term infants received a DTPa HBV-IPV-Hib vaccine at 1 1/2, 3 and 5 months of age; the other received a DTPa-IPV-Hib vaccine at 1 1/2, 3 and 5 months of age with separate HBV vaccine at 1 and 5 months of age. Immune response was similar following the two regimens with 100% of the vaccinees seroprotected for HBV, diphtheria, tetanus, Hib and poliovirus types 2 and 3 diseases after the full vaccination course. One vaccinee in the DTPa HBV-HPV- Hib group failed to respond to the poliovirus type 1 antigen. Response to the three pertussis antigens ranged from 92-97% in the DTPa-IPV-Hib plus separate HBV group and 100% in the DTPa HBV-IPV-Hib group. The most frequently reported post-vaccination symptoms were irritability in the DTPa-IPV-Hib plus separate HBV group (49% of vaccinees) and fever, defined as axillary temperature > or =37.5 degrees C, in the DTPa HBV- IPV-Hib group (50% of vaccinees).
Subject(s)
Antibodies, Bacterial/biosynthesis , Antibodies, Viral/biosynthesis , Diphtheria-Tetanus-Pertussis Vaccine/administration & dosage , Drug Interactions , Female , Haemophilus Vaccines/administration & dosage , Hepatitis B Vaccines/administration & dosage , Humans , Immunization Schedule , Infant , Infant, Newborn , Male , Poliovirus Vaccine, Inactivated/administration & dosage , Safety , Vaccines, Combined/adverse effects , Vaccines, Conjugate/adverse effects摘要
The reactogenicity and immunogenicity of three combined measles, mumps and rubella (MMR) vaccines and one administered with a varicella vaccine was studied in infants. The vaccines were Priorix (designated MeMuRu, Group 1), M-M-R II (Group 2), Triviraten (Group 3) and Priorix + a varicella vaccine, Varilrix (Group 4). Fever was greater in Group 2 (61.3%) compared to Group 1 (48.5%; p = 0.033) or Group 3 (37.1%; p = 0.009). Rash with fever was reported in Group 2 (4.8%) and Group 4 (3.3%), but not for Group 1. Anti-measles, -mumps and -rubella seroconversion was similar for Group 1 (96.1%, 96.1% and 100%, respectively), Group 4 (98% for all three), and Group 2 (91.5%, 93.6% and 97.9%) 60 days post-vaccination. GMTs for measles (3,053.7-3,412.2 mIU/ml), mumps (1,001.5-1,158.8 U/ml) and rubella (68.7-89.1 IU/ml) were similar for Groups 1, 2 and 4 at Day 60. Antibody persistence was noted 2 years post-vaccination. The MeMuRu + varicella combination showed no clinically relevant increase in reactogenicity and should facilitate introduction of a varicella vaccine into national immunization schedules.
Subject(s)
Antibodies, Viral/administration & dosage , Chickenpox Vaccine/administration & dosage , Female , Follow-Up Studies , Germany/epidemiology , Humans , Immunogenetics , Incidence , Infant , Infant Welfare , Injections, Intramuscular , Male , Measles-Mumps-Rubella Vaccine/administration & dosage , Randomized Controlled Trials as Topic , Reference Values , Treatment Outcome , Vaccines, Combined摘要
The epidemiology of varicella appears to be changing: an unexplained upward age shift in varicella prevalence and a subsequent dramatic rise in morbidity and mortality among adolescents and adults have highlighted the importance of effective varicella mass vaccination programs. This age shift is being seen in temperate regions but is particularly marked in tropical and sub-tropical regions. To assess the need for serological pre-screening in mass vaccination programs, we performed an open study to compare the reactogenicity and immunogenicity of a varicella vaccine in initially seronegative and seropositive subjects to see whether there was an increase in reactogenicity among initially seropositive subjects. Two hundred and forty-six seronegative and seropositive male and female subjects, aged 9 months to 60 years, received a single dose of a live attenuated varicella virus (Oka-strain) vaccine, Varilrix (GlaxoSmithKline Biologicals, Rixensart, Belgium). Subjects were categorized according to antibody status and age group; serum antibodies were measured before and after vaccination (day 42). The study showed that there was no difference in reactogenicity in initially seropositive vaccinees compared with initially seronegative subjects. The varicella vaccine was found to be safe and well tolerated in all age groups. Ninety-eight percent of initially seropositive and 94.8% of initially seronegative subjects reported no clinical signs or symptoms during the 42-day follow-up period. The vaccine was immunogenic in both groups. The seroconversion rate after 6 weeks in initially seronegative subjects was 94.3%. In 53.0% of initially seropositive subjects of all age classes, a 4-fold rise in antibody titer was observed.
Subject(s)
Adolescent , Antibodies, Viral/biosynthesis , Chickenpox Vaccine/administration & dosage , Child , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunization Programs , Male , Philippines摘要
Varicella infection may cause significant morbidity and mortality especially in immunocompromised persons. Children with chronic liver disease who undergo liver transplantation and need long term immunosuppressive therapy are at risk to acquire the infection. Twenty-nine children (aged 1-12 years) with chronic liver disease were enrolled to receive one dose of live attenuated varicella vaccine (Oka-strain). During the 16-week follow-up period, no vaccine-related serious adverse events were reported. Seroconversion rates at 8 weeks post vaccination were 100%. Geometric mean titer (GMT) values and seropositive rates at 16 weeks tended to relate to the clinical severity of liver disease. This study demonstrates that varicella vaccine is safe and Immunogenic in children with chronic liver disease.
Subject(s)
Chickenpox Vaccine/adverse effects , Child , Child Welfare , Child, Preschool , Chronic Disease , Female , Fever/etiology , Follow-Up Studies , Humans , Immunogenetics , Infant , Infant Welfare , Japan , Liver Diseases/complications , Male , Respiratory Tract Infections/etiology , Severity of Illness Index , Vaccines, Attenuated/adverse effects摘要
The availability of safe and effective vaccines has renewed interest in the epidemiology of varicella worldwide. To date published data on the epidemiology of varicella in Pakistan is very scarce. Therefore, we conducted a study to determine the age-specific seroprevalence rate of varicella-zoster virus (VZV) antibodies in Pakistan. Between December 1997 and March 1998, 1,509 healthy volunteers aged between 1 month and 30 years were recruited from the Islamabad, Karachi, Lahore and Rawalpindi areas. Demographic information, socioeconomic status and past medical history were obtained by questionnaire. Serum samples were assayed for IgG antibodies against VZV by enzyme-linked immunosorbent assay. Overall 41.8% (600/1,435) of those tested were found to be seropositive for VZV antibodies. No difference was found in results obtained from the different cities. A higher seroprevalence was observed among women (45.2%) compared to men (39.6%). Seroprevalence rates increased with age and were 28.4% in those aged 0-5 years, 41.5% in the 6-10 year age group, 42.5% in the 11-15 year age group, 46.7% in the 16-20 year age group and 53.6% in those aged 21-30 years. Socioeconomic status was not a significant risk factor for VZV seropositivity. This is the first report of the seroepidemiology of VZV in Pakistan. The results indicate that seroprevalence of VZV increases with age in the Pakistani population studied. As in other tropical countries, there is greater susceptibility to varicella among the adolescent and young adult population. The results of this study suggest that these at-risk groups should be included in vaccination programs aimed at reducing the public health impact of varicella.
Subject(s)
Adolescent , Adult , Antibodies, Viral/blood , Chickenpox/blood , Child , Cross-Sectional Studies , Enzyme-Linked Immunosorbent Assay , Female , Herpesvirus 3, Human/enzymology , Humans , Immunization Programs/organization & administration , Male , Pakistan/epidemiology , Seroepidemiologic Studies , Social Class摘要
OBJECTIVE: To determine the age related prevalence of Varicella Zoster Virus (VZV) antibodies in India. SETTING: This was a cross sectional multicentric study performed in 4 major cities of India: Calcutta (outpatients), Mumbai (outpatients), Lucknow (walk-in patients to a diagnostic laboratory, orphanage and factory workers) and Bangalore (outpatients and walk-in patients to a diagnostic laboratory). METHODS: A total of 1609 volunteers from birth to 40 years of age were included into the study. IgG antibodies against VZV were determined using commercial kits (ELISA-Enzygnost). RESULTS: Overall seroprevalence of anti VZV antibodies was 68. 22percnt. The age related seroprevalence rate of anti VZV antibodies was 29percnt in the age group of 1-5 years, 51.1percnt in 5-10 years, 71.7percnt in 11-15 years, 79.8percnt in 16-20 years, 88.1percnt in 21-30 years and 91.1percnt in 31-40 years. CONCLUSION: A significant proportion of adolescents and adults are susceptible to varicella in India, as in other tropical countries
Subject(s)
Adolescent , Adult , Age Distribution , Chickenpox/epidemiology , Child , Child, Preschool , Cross-Sectional Studies , Herpesvirus 3, Human/immunology , Humans , India/epidemiology , Infant , Infant, Newborn , Seroepidemiologic Studies摘要
Hepatitis A virus (HAV) cause an acute inflammation of the liver. Varicella-zoster virus (VZV) cause chickenpox (varicella) and herpes zoster. Effective vaccines against hepatitis A and varicella are available for children, adolescents and adults. In order to implement an appropriate vaccination policy, a baseline to assess the potential benefits and sections of the population who would benefit most are required. We investigated seroprevalence of hepatitis A virus and varicella zoster antibodies in a Javanese community. A total of 1,103 subjects were studied. The 600 subjects aged 4 to 9 years were sampled between 23 October and 2 November, 1995. The other subjects were sampled between 12 October and 1 November, 1996. The overall prevalence of anti-HAV in cohort was 28.7%. Anti-HAV seroprevalence rates were below 30% until the age of 15 and below 40% until the age of 25. The anti-varicella seroprevalence showed only in two thirds of seropositive population at the age of 15. The results of the study have implications for vaccination strategies for both hepatitis A and varicella zoster.
Subject(s)
Adolescent , Adult , Antibodies, Viral/blood , Chickenpox/epidemiology , Child , Child, Preschool , Cohort Studies , Female , Hepatitis A/epidemiology , Hepatitis A Antibodies , Hepatitis Antibodies/blood , Hepatovirus/immunology , Herpesvirus 3, Human/immunology , Humans , Indonesia/epidemiology , Male , Prevalence , Seroepidemiologic Studies摘要
An open, randomized multi-center trial, involving 700 infants, was conducted in order to compare a new measles mumps rubella (MMR) vaccine, SB MMR (containing a Jeryl Lynn derived mumps strain RIT 4385) with a widely used vaccine, Merck MMR, when given to children between 12-24 months. Infants were divided between 2 groups; group 1 received SB MMR while group 2 received Merck MMR. Solicited local and general symptoms were recorded using diary cards and antibody levels were measured using ELISA assays. There was a significantly lower incidence of redness (p < 0.001) and swelling (p = 0.03) observed in group 1 compared with group 2. The incidence of all other solicited local and general symptoms were comparable between groups. In initially seronegative subjects equivalent seroconversion rates and post-vaccination GMTs were observed between groups. In conclusion, these results demonstrate that SB MMR is safe and well tolerated when given to children at this age range, and has an equivalent immunogenic profile compared to the widely used Merck MMR vaccine.
Subject(s)
Analysis of Variance , Antibody Formation , Child, Preschool , Enzyme-Linked Immunosorbent Assay , Female , Fever/etiology , Humans , Infant , Male , Measles/immunology , Measles Vaccine/administration & dosage , Measles-Mumps-Rubella Vaccine , Mumps/immunology , Mumps Vaccine/administration & dosage , Philippines , Rubella/immunology , Rubella Vaccine/administration & dosage , Seizures/etiology , Vaccines, Combined/administration & dosage摘要
An open, randomized, clinical trial was conducted in order to assess the reactogenicity and immunogenicity of DTPw-HBV and Haemophilus influenzae type b (Hib) vaccines when given either as a mixed administration or as separate concomitant injections using the WHO schedule at 6, 10 and 14 weeks of age, following a dose of HBV at birth. There were no clinically relevant differences in the immune response to any component between the mixed and separate administrations. In fact the anti-tetanus GMTs were significantly higher (p=0.002) in mixed administration (3.9 IU/ml) compared with the separate administration (1.9 IU/ml). However although all subjects achieved anti-PRP titers > or = 0.15 microg/ml, higher anti-PRP GMTs were seen in the group receiving the separate administration. Importantly, the addition of Hib did not adversely alter the reactogenicity profile of DTPw-HBV. This report which demonstrates that this novel combination can be used in WHO recommended schedule.