RESUMEN
Several studies have investigated a possible association between the ABO blood group and the risk of pancreatic cancer (PC), but this association has not been fully evaluated in Asian populations. The present study aimed to assess the impact of genotype-derived ABO blood types, particularly ABO alleles, on the risk of PC in a Japanese population. We conducted a case-control study using 185 PC and 1465 control patients who visited Aichi Cancer Center in Nagoya, Japan. Using rs8176719 as a marker for the O allele, and rs8176746 and rs8176747 for the B allele, all participants' two ABO alleles were inferred. The impact of ABO blood type on PC risk was examined by multivariate analysis, with adjustment for potential confounders to estimate odds ratios (OR) and 95% confidence intervals (CI). An increased risk of PC was observed with the addition of any non-O allele (trend P = 0.012). Compared with subjects with the OO genotype, those with AO and BB genotypes had significantly increased OR of 1.67 (CI, 1.08-2.57) and 3.28 (CI, 1.38-7.80), respectively. Consistent with earlier reports showing a higher risk of PC for individuals with the non-O blood type, the previously reported protective allele (T) for rs505922 was found to be strongly correlated (r(2) = 0.96) with the O allele. In conclusion, this case-control study showed a statistically significant association between ABO blood group and PC risk in a Japanese population. Further studies are necessary to define the mechanisms by which the ABO gene or closely linked genetic variants influence PC risk.
Asunto(s)
Sistema del Grupo Sanguíneo ABO/genética , Predisposición Genética a la Enfermedad/epidemiología , Neoplasias Pancreáticas/sangre , Neoplasias Pancreáticas/epidemiología , Adulto , Anciano , Alelos , Pueblo Asiatico/genética , Estudios de Casos y Controles , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de RiesgoRESUMEN
The frequencies of human leukocyte antigen (HLA) alleles HLA-A, -B, and -DRB1 alleles and A-B-DRB1, A-B, and B-DRB1 haplotypes were studied in Jinuo and Wa populations in Southwest China using the polymerase chain reaction-Luminex (PCR-Luminex) typing method. A total of 12 A, 22 B, and 16 DRB1 alleles were found in the Jinuo population, and 10 A, 28 B, and 18 DRB1 alleles were found in the Wa population. The A*110101-B*1502-DRB1*120201 was the predominant haplotype in both the Jinuo and Wa populations; A*110101-B*1301-DRB1*120201 and A*24020101-B*1502-DRB1*120201 were common in the Jinuo population, whereas A*110101-B*1532-DRB1*1504 and A*110101-B*350101-DRB1*1404 were common in the Wa population. Phylogenetic tree and principal component analyses based on HLA-A, -B, and -DRB1 allele frequencies suggested that both the Jinuo and Wa populations belong to the Southeast Asian group, whereas Wa population is still maintaining its original genetic character and a great distance from other populations because of a founder effect and subsequent geographic isolation. A close relationship among Jinuo, Wa, Thai, and Vietnamese was also suggested.
Asunto(s)
Frecuencia de los Genes , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-DR/genética , China/etnología , Cadenas HLA-DRB1 , Haplotipos , Humanos , Filogenia , Análisis de Componente PrincipalRESUMEN
BACKGROUND: Reports suggest a relationship between circulating sex hormone levels and breast cancer risk, but genetic association studies have been inconclusive. We investigated the association between levels of sex hormones and single nucleotide polymorphisms (SNPs) in genes coding for the enzymes that regulate them. METHODS: We assayed circulating levels of estradiol, testosterone, estrone, androstenedione, 17alpha-hydroxyprogesterone, and sex hormone-binding globulin (SHBG) in 1975 normal postmenopausal women. Fifteen SNPs in the CYP17, CYP19, EDH17B2, SHBG, COMT, and CYP1B1 genes were genotyped in these postmenopausal women and in a breast cancer case-control study. Associations of genotypes with breast cancer risk were evaluated in the case-control study and with hormone levels in the postmenopausal women using multiple linear regression with assay batch, body mass index, parity, peri- or postmenopausal status, and age band as covariates. RESULTS: CYP19 SNPs (rs10046 and [TCT]+/-) were associated with differences in estradiol level (P =.0006 and P =.0003, respectively) and the estradiol : testosterone ratio (P =.000001() and P =.002). SNP rs10046 explained 1.6% of the variance (r2) in the estradiol : testosterone ratio. SHBG SNPs (5' untranslated region [5'UTR] g-a and D356N) were associated with both SHBG levels (P<10(-6) and P =.005) and the estradiol : SHBG ratio (P =().000008() and P =.01). These SNPs explained 2.4% and 0.6% of the variance in SHBG levels, respectively. SNPs in the other genes were not associated with differences in any hormone levels, and none were statistically significantly associated with breast cancer risk. CONCLUSION: Genetic variation in CYP19 and SHBG contributes to variance in circulating hormone levels between postmenopausal women, but low r2 values may explain why these genes have given inconclusive results in breast cancer case-control studies.