HLA-A alleles and the risk of cervical squamous cell carcinoma in Japanese women.

BACKGROUND: We conducted a case-control study to examine the relationship between human leukocyte antigen-A (HLA-A) allele polymorphism and the pathogenesis of cervical neoplasia among Japanese women. METHODS: A total of 119 patients with invasive cervical squamous cell carcinoma were compared to 119 age- and menopausal status-matched non-cancer controls. Blood samples were taken from all cases and controls and lifestyle information was collected by means of a self-administered questionnaire. The estimated impact of HLA-A alleles on cervical cancer risk was evaluated by unconditional logistic regression models. RESULTS: The frequency of HLA-A(*)0206 among cases was significantly lower than among controls (P = 0.006). There was an inverse association between A(*)0206 and cervical cancer risk (odds ratio [OR] = 0.31, 95% confidence interval [95% CI] = 0.15 to 0.65, P = 0.002), and a positive association for HLA-A(*)2402 (OR = 1.76, 95% CI = 1.00 to 3.09, P = 0.048). After correction for multiple comparisons, A(*)0206 was significantly associated with reduced cervical cancer risk (corrected P = 0.036). Furthermore, the inverse association between A(*)0206 and cervical cancer risk was independent of smoking status (never smoker: OR = 0.37, 95% CI = 0.15 to 0.90; ever smoker: OR = 0.23, 95% CI = 0.06 to 0.89). CONCLUSIONS: There was an inverse association between HLA-A(*)0206 and cervical cancer risk among Japanese women, which suggests that HLA-A polymorphism influences cervical cancer risk. Further investigation in other populations is thus warranted.

Association between CYP19A1 polymorphisms and sex hormones in postmenopausal Japanese women.

In postmenopausal women, extraovarian sex hormone production plays an important role in hormone-related diseases, such as breast and endometrial cancers. Aromatase, an enzyme encoded by CYP19A1, is a key enzyme involved in estrogen biosynthesis. The impact of CYP19A1 polymorphisms on serum sex hormone levels in the Japanese population has never been investigated. This study enrolled 100 postmenopausal Japanese women found to be without cancer. Twenty-five CYP19A1 loci were identified, and measurements were conducted on serum levels of sex hormones; lifestyle data were collected, namely estrone (E1), estradiol (E2), testosterone and sex hormone-binding globulin (SHBG). We conducted a cross-sectional analysis to evaluate the impact of CYP19A1 haplotype on serum sex hormone levels. We found that subjects with BMI>or=25 kg/m(2) showed a significant difference in circulating testosterone levels (0.29+/-0.19, P=0.050). Neither age nor the amount of physical exercise or drinking habits showed any effect on hormone levels. We identified seven haplotype blocks in CYP19A1 by LD analysis. Estrone levels differed in rs12148604 (SNP 1) and rs11632903 (SNP14). No significant locus for estradiol was observed. SHBG levels were associated with rs4441215 (SNP11). Testosterone levels were strongly associated with rs752760 (SNP24) and rs2445768 (SNP25) and weakly associated with SNP 1, SNP11 and SNP14 as well. We found that polymorphisms in CYP19A1 influence sex hormone levels in Japanese postmenopausal women.

Reduced risk of endometrial cancer from alcohol drinking in Japanese.

The role of alcohol consumption in the etiology of endometrial cancer has not been clarified. To examine the association between alcohol consumption and endometrial cancer risk, we conducted a case-control study with 148 histologically diagnosed incident endometrial cancer cases and 1468 matched non-cancer controls. Median consumption of alcohol was only 19.3 g/week among cases who drank and 28.2 g/week among controls who drank. These values are lower than in Western countries. Relative risk was analyzed in subjects classified into four groups according to weekly alcohol consumption (non-drinkers, 1-24 g/week, 25-175 g/week, and >175 g/week). Confounder-adjusted odds ratios for those consuming alcohol at <25 g/week, 25-175 g/week, and >175 g/week compared to non-drinkers were 0.79 (95% confidence interval (CI), 0.49-1.28), 0.42 (95% CI, 0.23-0.79), and 0.47 (95% CI, 0.14-1.58), respectively. Further analysis was conducted concerning self-reported physical reaction to alcohol. Among women without flushing after drinking, a significant inverse association between risk and alcohol intake was seen (trend P = 0.001). In contrast, no protective effect of alcohol was seen among women who experience flushing after drinking. These results suggest the presence of an inverse association between alcohol drinking and endometrial cancer risk among Japanese women, and that this association is evident among those without flushing. Further investigation of these findings is warranted.

[Neoadjuvant chemotherapy with intra-arterial infusion in the treatment of advanced cervical cancer].

Neoadjuvant chemotherapy (NAC) with intra-arterial infusion was performed in the treatment for 53 patients with advanced cervical squamous cell carcinoma. After NAC with intra-arterial infusion of the anticancer agents including cisplatin via internal iliac artery or uterine artery, 42 patients received radical hysterectomy. The response to therapy was observed in 45 of all patients (84.9%) clinically, and 36 of 42 patients (85.7%) pathologically. Cancer cells disappeared in 11.9% of patients with cervical invasion, 69.2% with vaginal wall invasion and 39.4% with parametrium invasion after NAG. Five-year survival rates were 100% in stage I, 71.5% in stage II, 52.2% in stage II and 0% in stage IV. The group of patients without cancer in the parametrium after NAC showed a significantly better 5-year survival rate than the group with residual cancer in the parametrium. According to the results, the elimination of cancer invasion to the parametrium by NAC is thought to be important for improvement of the prognosis in advanced cervical cancer.

Amniotic fluid neutrophil elastase and lactate dehydrogenase: association with histologic chorioamnionitis.

BACKGROUND: Chorioamnionitis (CAM) is considered to be one of the main causes of preterm labor and has been associated with an adverse perinatal outcome in preterm infants. The diagnosis of acute histologic CAM requires delivery and examination of the placenta. Although numbers of markers have been reported to predict histologic CAM before birth, it is unknown whether the levels of neutrophil elastase and lactate dehydrogenase (LDH) in amniotic fluid are associated with histologic CAM. METHODS: Sixty women at gestational age of 16-35 weeks underwent transabdominal amniocentesis within 48 hr before delivery. Amniotic fluid was analyzed for white blood cell count, glucose level, LDH level, and neutrophil elastase level. The levels of neutrophil elastase were measured by latex immunoassay. Following delivery, tissue samples were obtained from umbilical cord, chorionic plate, and placental membranes. Histologic CAM was diagnosed based on Blanc's criteria. RESULTS: Receiver-operator characteristic curve analysis showed that the amniotic fluid neutrophil elastase had the best screening efficiency in predicting histologic CAM. Using amniotic fluid cut-off levels of 0.15 microg/ml for neutrophil elastase and 250 IU/l for LDH, the sensitivity, specificity, and positive and negative predictive values for predicting histologic CAM were 88.9% versus 84.1%, 73.3% versus 66.7%, 90.9% versus 88.1%, and 68.8% versus 58.8%, respectively. CONCLUSION: Amniotic neutrophil elastase and LDH are useful markers in predicting histologic CAM.