Association of serum asymmetric dimethylarginine, homocysteine, and l-arginine concentrations during early pregnancy with hypertensive disorders of pregnancy.

BACKGROUND: Our previous study suggested that a lower l-arginine level (<70µM) at early gestation is associated with pregnancy-induced hypertension. The maternal asymmetric dimethylarginine (ADMA) and homocysteine (Hcy) concentrations also have been reported to be increased in hypertensive disorders of pregnancy (HDP). These molecules have a key role in metabolism of nitric oxide. The aim of this study is to determine the most useful predictor of HDP at early gestation. METHODS: The concentrations of ADMA and Hcy at each of three periods in normal pregnancy were determined, and the values compared between the normal pregnancy and HDP groups. Moreover, the possible risk factors for the development of HDP also were evaluated using a multivariate logistic regression model and propensity score (PS). RESULTS: The maternal ADMA concentration was significantly elevated with advance of gestational age, while Hcy concentration was decreased from early to mid-gestation and increased from mid- to late-gestation in normal pregnancy. The maternal Hcy concentration at early gestation was significantly higher in the HDP group compared to that in the normal group. A higher maternal Hcy level (>7.2µM) in early pregnancy was independently associated with the development of HDP (PS-adjusted odds ratio=4.47, 95% confidence interval=1.51-12.82), as well as pre-pregnancy overweight [body mass index (BMI)>25kg/m2], primipara status, and a lower maternal l-arginine level (<70µM). CONCLUSIONS: The risk factors, such as overweight (BMI>25kg/m2) before pregnancy, primipara status, higher Hcy (>7.2µM), and lower l-arginine (<70µM) concentration in early pregnancy, for development of HDP were detected.

Is the serum l-arginine level during early pregnancy a predictor of pregnancy-induced hypertension?

The objective of this study was to determine the concentration of serum l-arginine in healthy pregnant women and infant cord blood and to compare them with those in patients with pregnancy-induced hypertension (PIH). The serum concentration of l-arginine in normal pregnant women at early gestation (n = 186) was determined and analyzed based on maternal factors such as the age, pre-pregnancy body mass index (BMI), smoking and alcohol habits before pregnancy. Similarly, the concentration of cord blood of the newborns (n = 142) was also analyzed. These values were compared with those in the PIH group (n = 21). The potential risk factors for PIH were also estimated. The serum concentration of l-arginine at early gestation in normal pregnant women (88.65 ± 19.96 µM) was not affected by the maternal age and BMI before pregnancy. A lower l-arginine concentration at early gestation (<70 µM) significantly elevated PIH risk [adjusted odds ratio (OR) = 4.26, 95% CI 1.29-14.50]. In addition, either women with large body mass before pregnancy (BMI>25 kg/m(2)) or primipara women also showed a significant association with PIH risk [adjusted OR = 10.55 (2.95-40.68); 5.25 (1.72-19.15), respectively]. In conclusion, a lower l-arginine concentration at early gestation, overweight before pregnancy (BMI>25 kg/m(2)) and primipara could predict to the development of PIH.

TP53 codon 72 polymorphism and cervical cancer: a pooled analysis of individual data from 49 studies.

BACKGROUND: Cervical cancer is caused primarily by human papillomaviruses (HPV). The polymorphism rs1042522 at codon 72 of the TP53 tumour-suppressor gene has been investigated as a genetic cofactor. More than 80 studies were done between 1998 and 2006, after it was initially reported that women who are homozygous for the arginine allele had a risk for cervical cancer seven times higher than women who were heterozygous for the allele. However, results have been inconsistent. Here we analyse pooled data from 49 studies to determine whether there is an association between TP53 codon 72 polymorphism and cervical cancer. METHODS: Individual data on 7946 cases and 7888 controls from 49 different studies worldwide were reanalysed. Odds ratios (OR) were estimated using logistic regression, stratifying by study and ethnic origin. Subgroup analyses were done for infection with HPV, ethnic origin, Hardy-Weinberg equilibrium, study quality, and the material used to determine TP53 genotype. FINDINGS: The pooled estimates (OR) for invasive cervical cancer were 1.22 (95% CI 1.08-1.39) for arginine homozygotes compared with heterozygotes, and 1.13 (0.94-1.35) for arginine homozygotes versus proline homozygotes. Subgroup analyses showed significant excess risks only in studies where controls were not in Hardy-Weinberg equilibrium (1.71 [1.21-2.42] for arginine homozygotes compared with heterozygotes), in non-epidemiological studies (1.35 [1.15-1.58] for arginine homozygotes compared with heterozygotes), and in studies where TP53 genotype was determined from tumour tissue (1.39 [1.13-1.73] for arginine homozygotes compared with heterozygotes). Null results were noted in studies with sound epidemiological design and conduct (1.06 [0.87-1.29] for arginine homozygotes compared with heterozygotes), and studies in which TP53 genotype was determined from white blood cells (1.06 [0.87-1.29] for arginine homozygotes compared with heterozygotes). INTERPRETATION: Subgroup analyses indicated that excess risks were most likely not due to clinical or biological factors, but to errors in study methods. No association was found between cervical cancer and TP53 codon 72 polymorphism when the analysis was restricted to methodologically sound studies. FUNDING: German Research Foundation (DFG).

Active smoking, passive smoking, and breast cancer risk: findings from the Japan Collaborative Cohort Study for Evaluation of Cancer Risk.

BACKGROUND: Evidence is lacking regarding the relationship between cigarette smoking and breast cancer in Japanese women. We examined the association between breast cancer incidence and active and passive smoking in the Japan Collaborative Cohort Study for Evaluation of Cancer Risk. METHODS: Our study comprised 34,401 women aged 40-79 years who had not been diagnosed previously with breast cancer and who provided information on smoking status at baseline (1988-1990). The subjects were followed from enrollment until December 31, 2001. Cox proportional-hazards models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the association between breast cancer incidence and tobacco smoke. RESULTS: During 271,412 person-years of follow-up, we identified 208 incident cases of breast cancer. Active smoking did not increase the risk of breast cancer, with a HR for current smokers of 0.67 (95% CI: 0.32-1.38). Furthermore, an increased risk of breast cancer was not observed in current smokers who smoked a greater number of cigarettes each day. Overall, passive smoking at home or in public spaces was also not associated with an increased risk of breast cancer among nonsmokers. Women who reported passive smoking during childhood had a statistically insignificant increase in risk (HR: 1.24; 95% CI: 0.84-1.85), compared with those who had not been exposed during this time. CONCLUSION: Smoking may not be associated with an increased risk of breast cancer in this cohort of Japanese women.

Consumption of soy foods and the risk of breast cancer: findings from the Japan Collaborative Cohort (JACC) Study.

OBJECTIVE: The association between a lower incidence of breast cancer within the Asian population and the consumption of a diet high in soy has recently been the subject of much attention. To examine whether soy foods really have protective effects against breast cancer and how their influence on breast cancer is modified according to menopausal status, we conducted a population-based, prospective cohort study in Japan. METHODS: We analyzed the data from the Japan Collaborative Cohort (JACC) Study. From 1988 to 1990, 30,454 women aged 40-79 years, completed a questionnaire on diet and other lifestyle features. Hazard ratios (HRs) were computed to examine the association between soy intake and the risk of breast cancer. RESULTS: During the mean follow-up of 7.6 years, 145 cases of breast cancer were documented. We found no significant association between the risk of breast cancer and consumption of tofu, boiled beans, and miso soup; the multivariate HRs (95% CI) in the highest category of consumption were 1.14 (0.74-1.77), 0.77 (0.47-1.27) and 1.01 (0.65-1.56), respectively. Only among postmenopausal women, we found no significant associations between soy foods and the risk of breast cancer. CONCLUSIONS: This prospective study suggests that consumption of soy food has no protective effects against breast cancer. Further large-scale investigations eliciting genetic factors may clarify different roles of various soybean-ingredient foods on the risk of breast cancer.

Psychological attitudes and risk of breast cancer in Japan: a prospective study.

OBJECTIVE: To examine the association between psychological factors and the risk of breast cancer prospectively in a non-Western population. METHODS: Data from the Japan Collaborative Cohort (JACC) study were analyzed. From 1988 to 1990, 34,497 women aged 40-79 years completed a questionnaire on medical, lifestyle and psychosocial factors. The rate ratios (RRs) of their responses were computed by fitting to proportional hazards models. RESULTS: During the mean follow-up period of 7.5 years, 149 breast cancer cases were documented. Those individuals who possessed "ikigai" (Japanese term meaning something that made one's life worth living) showed a significantly lower risk of breast cancer (multivariate-adjusted RR=0.66; 95% confidence interval [CI]=0.47-0.94). Those who perceived themselves as able to make decisions quickly also had a lower risk of breast cancer (multivariate-adjusted RR=0.56; 95% CI=0.36-0.87). The other factors investigated, including ease of anger arousal and self-perceived stress of daily life were not associated with breast cancer risk. CONCLUSIONS: Although further studies will be necessary to verify these findings, our results suggest that having "ikigai" and being decisive decrease an individual's subsequent risk of breast cancer.

Coffee consumption and the risk of endometrial cancer: Evidence from a case-control study of female hormone-related cancers in Japan.

Coffee has become a popular beverage worldwide. Caffeine, a major ingredient of coffee, has been proposed to have a favorable affect on the modulation of circulating estrogen levels and therefore may be of importance in developments on hormone-related cancers. However, epidemiological evidence is limited and inconsistent. We examined the relationship between intake of coffee and hormone-related cancer risk among Japanese women using data from the hospital-based epidemiological research program at Aichi Cancer Center (HERPACC). In total, 2122 breast, 229 endometrial and 166 ovarian cancer cases were included, and 12 425 women, confirmed as free of cancer, were recruited as the control group. Odds ratios (OR) and 95% confidence intervals (95% CI) were determined by multiple logistic regression analysis. A statistically significant inverse association between risk of endometrial cancer and coffee consumption was noted in Japanese women, with no clear association evident for breast and ovarian cancer risk. Compared to non-drinker, the OR of daily drinking of 1-2 cups and 3 or more cups per day for endometrial cancer were 0.64 (95% CI: 0.43-0.94) and 0.41 (95% CI: 0.19-0.87), respectively, and the linear trend was also statistically significant (P < 0.01). However, there was no statistically significant association between caffeine intake and endometrial cancer. In summary, the results of the present study suggest that coffee consumption reduces the risk of endometrial cancer in Japanese subjects. Given the scarcity of studies of coffee intake and endometrial cancer and other hormone-dependent cancer risk, additional investigations are warranted.

Lymphotoxin-alpha polymorphisms and the risk of endometrial cancer in Japanese subjects.

OBJECTIVE: To test the association of endometrial cancer with the lymphotoxin-alpha (LTalpha) C804A and A252G polymorphisms, a hospital-based incident case-control study was performed in Japanese subjects. METHODS: The cases comprised 110 endometrial cancer patients, and the controls were 220 age-matched cancer-free females. RESULTS: The LTalpha C804A and A252G polymorphisms were in complete linkage disequilibrium. We performed conditional logistic regression analysis adjusted for age, which revealed that the LTalpha 252AG and 804CA variant genotypes were associated with a significantly reduced risk of endometrial cancer (OR=0.51, 95% CI=0.31-0.86, P=0.011). Being homozygous of the LTalpha 252G and 804A alleles was not associated with the risk of endometrial cancer. However, the presence of at least one variant LTalpha allele was associated with a significantly lower risk of endometrial cancer (OR=0.54, 95% CI=0.33-0.87, P=0.012). After adjusting for potential confounders (body mass index, age at menarche, parity, hypertension, diabetes mellitus, family history of endometrial cancer, hormone replacement therapy, smoking status, and alcohol consumption), the risk of endometrial cancer was significantly lower both in carriers of one variant allele and in carriers of either one or two of the variant alleles (OR=0.47, 95% CI=0.26-0.85, P=0.017; OR=0.50, 95% CI=0.28-0.89, P=0.019; respectively). CONCLUSION: The results suggest that these LTalpha polymorphisms play an important role in the tumorigenesis of endometrial cancer.

Relationship between body mass index and the risk of ovarian cancer in the Japanese population: findings from the Japanese Collaborate Cohort (JACC) study.

AIM: The incidence of ovarian cancer in Japan has increased since the 1970s. The many studies that have assessed the relationship between body mass index (BMI) and the risk of ovarian cancer have produced contradictory results. Here we investigated this relation using data from the Japan Collaborative Cohort Study for the Evaluation of Cancer Risk, which was initiated in 1988. METHODS: A self-administered questionnaire on dietary habits and other risk factors for cancer was completed by 36,456 Japanese women. After 7.6 years of follow up, 38 cases of ovarian cancer were available for analysis. Cox proportional-hazards models were used to compute relative risks and to adjust for confounders. RESULTS: Compared to women with BMI of 18.5-24.9 kg/m2, the relative risk of ovarian cancer was 2.24 (95% CI = 1.10-4.21) for BMI of 25.0-29.9 and 1.78 (95% CI = 0.24-13.34) for BMI of > or = 30 kg/m2. A test for trend revealed that this finding was statistically significant (P = 0.014). CONCLUSION: The results of this study suggest that being overweight is independently associated with a higher risk of developing ovarian cancer in the Japanese population.

Use of duplex PCR-CTPP methods for CYP2E1RsaI/IL-2 T-330G and IL-1B C-31T/TNF-A T-1031C polymorphisms.

BACKGROUND: Two duplex polymerase chain reaction (PCR) with confronting two-pair primer (PCR-CTPP) methods were designed for cytochrome P450 (CYP) 2E1 RsaI and interleukin (IL-2) T-330G, and for IL-1B C-31T and tumor necrosis factor-alpha (TNF-A) T-1031C. The four polymorphisms are considered to be functional, and the three cytokines reportedly inhibit CYP2E1 expression. Many studies have reported associations between the above polymorphisms and risk of diseases including cancers and inflammatory diseases. AIM: The main objective of this study was to examine the applicability of the established PCR conditions to a real situation. PARTICIPANTS: Participants were female examinees aged from 35 to 85 years who attended health checks run by a local government in Japan. RESULTS: The allele frequencies among 325 female health check examinees were 0.804 for CYP2E1 c1 allele, 0.668 for IL-2-330T allele, 0.554 for IL-1B-31T allele, and 0.822 for TNF-A-1031T allele. p-Values from a Hardy-Weinberg equilibrium test were 0.658, 0.955, 0.062, and 0.806, respectively. DISCUSSION: Clear DNA bands observed with electrophoresis allowed us to genotype the four polymorphisms. The genotype frequencies were within the Hardy-Weinberg equilibrium test proportions, though the p-value for IL-1B C-31T was marginal. CONCLUSIONS: Both duplex PCR-CTPP methods may be useful tools for studies on the association between these polymorphisms and disease risk.

Dietary intakes of fat and fatty acids and risk of breast cancer: a prospective study in Japan.

To examine the possible association of dietary fat and fatty acids with breast cancer risk in a population with a low total fat intake and a high consumption of fish, we analyzed data from the Japan Collaborative Cohort (JACC) Study. From 1988 to 1990, 26 291 women aged 40-79 years completed a questionnaire on dietary and other factors. Intakes of fat or fatty acids were estimated by using a food frequency questionnaire. Rate ratios (RR) were computed by fitting proportional hazards models. During the mean follow-up of 7.6 years, 129 breast cancer cases were documented. We found no clear association of total fat intake with breast cancer risk; the multivariate-adjusted RR across quartiles were 1.00, 1.29, 0.95, and 0.80 (95% confidence interval [CI] 0.46-1.38). A significant decrease in the risk was detected for the highest quartile of intake compared with the lowest for fish fat and long-chain n-3 fatty acids; the RR were 0.56 (95% CI 0.33-0.94) and 0.50 (0.30-0.85), respectively. A decreasing trend in risk was also suggested with an increasing intake of saturated fatty acids (trend P = 0.066). Among postmenopausal women at baseline, the highest quartile of vegetable fat intake was associated with a 2.08-fold increase in risk (95% CI 1.05-4.13). This prospective study did not support any increase in the risk of breast cancer associated with total or saturated fat intake, but it suggested the protective effects of the long-chain n-3 fatty acids that are abundant in fish.

Association of XRCC1 Arg399Gln and OGG1 Ser326Cys polymorphisms with the risk of cervical cancer in Japanese subjects.

OBJECTIVE: In this study, genetic polymorphisms, XRCC1 Arg399Gln and OGG1 Ser326Cys were examined with reference to cervical cancer risk in a population-based incident case-control study in Japan. METHODS: The cases comprised 131 cervical cancer patients: 87 cases with squamous cell carcinoma (SCC) and 44 with adenocarcinoma (ADC) or adenosquamous carcinoma (ADSC). Controls were sampled from 320 healthy women who underwent a health checkup. RESULTS: The frequency of the XRCC1 399GlnGln genotype was higher in individuals with adenocarcinoma/adenosquamous carcinoma than in the healthy controls (OR = 2.98, 95% CI = 1.11-8.01, P = 0.030). However, no association was demonstrated in SCC. Analysis of OGG1 Ser326Cys polymorphism showed no significant differences between cervical cancer patients and controls. In stratification analysis, significant elevated risk of adenocarcinoma/adenosquamous carcinoma was associated with the XRCC1 399GlnGln genotype among nonsmokers (OR = 3.85, 95% CI = 1.28-11.59, P = 0.017), but not among smokers. No gene-gene interaction was observed in our case subjects. CONCLUSION: This is the first report that the XRCC1 Arg399Gln polymorphism might be important in relation to the risk of adenocarcinoma/adenosquamous carcinoma of the cervix.

Cigarette smoking and the risk of ovarian cancer in the Japanese population: findings from the Japanese Collaborate Cohort study.

AIM: The many studies into the relation between cigarette smoking and the risk of ovarian cancer have produced inconsistent results. Here we investigated this relation using data from the Japan Collaborative Cohort Study for Evaluation of Cancer Risk, initiated in 1988. METHODS: A self-administered questionnaire on smoking habits and other risk factors for cancer was completed by 34 639 Japanese women. After 7.6 years of follow up, 39 cases of ovarian cancer were available for analyses. Cox proportional-hazards models were used to compute relative risks (RR) and to adjust for confounders. RESULTS: Relative to those who had never smoked, the RR of ovarian cancer were 1.63 (95% confidence interval [CI] = 0.21-12.50) for former smokers and 2.27 (95% CI = 0.85-6.08) for current smokers. Among current smokers, the RR were 1.48 (95% CI = 0.20-10.92), 5.56 (95% CI = 1.68-19.06), and 1.86 (95% CI = 0.25-14.30) among women who smoked <10, 10-19, and at least 20 pack-years ([number of cigarettes smoked per day/20] x number of years subject has smoked), respectively, relative to those who had never smoked. A test for trend was statistically significant (P = 0.044). CONCLUSIONS: These data indicate that cigarette smoking increases the risk of developing ovarian cancer in the Japanese population.

Association of p73 G4C14-to-A4T14 polymorphism at exon 2 and p53 Arg72Pro polymorphism with the risk of endometrial cancer in Japanese subjects.

To test the association of endometrial cancer with the p73 G4C14-to-A4T14 polymorphism in exon 2 and the p53 Arg72Pro polymorphism, an incident case-control study was performed in Japanese subjects. The cases comprised 114 endometrial cancer patients, and the controls were 320 healthy females and 122 noncancer female outpatients. An unconditional logistic regression model demonstrated a significant association between the p73 AA genotype and an increased risk of endometrial cancer (OR=2.82, 95% CI=1.36-5.82), especially of type-I tumors (OR=3.24, 95% CI=1.53-6.87). In contrast, there was no significant difference in the p53 Arg72Pro genotype frequency between the controls and cases.

Association of the NAD(P)H: quinone oxidoreductase C609T polymorphism and the risk of cervical cancer in Japanese subjects.

OBJECTIVE: In this study, genetic polymorphisms, NQO1 C609T, GSTM1 positive/null, and GSTT1 positive/null, were examined with reference to cervical cancer risk in a population-based incident case-control study in Japanese. METHODS: The cases comprised 131 cervical cancer patients: 87 cases with squamous cell carcinoma (SCC) and 44 with adenocarcinoma (ADC) or adenosquamous carcinoma (ADSC). Controls were sampled from 320 healthy women who underwent a health checkup. RESULTS: The cervical cancer risk was substantially elevated with smoking for all cases, SCC cases, and ADC/ADSC cases (OR = 4.50, 95% CI = 2.48-8.17, P < 0.001; OR = 5.68, 95% CI = 2.99-10.78, P < 0.001; and OR = 2.57, 95% CI = 1.09-6.08, P = 0.032; respectively). The frequency of the NQO1 609TT genotype, reported to be associated with null enzyme activity, was higher in individuals with all cases and SCC than in the healthy controls (OR = 1.97, 95% CI = 1.06-3.66, P = 0.032; and OR = 2.42, 95% CI = 1.21-4.82, P = 0.012; respectively), but not in ADC/ADSC cases. Analysis of polymorphisms for GSTM1 and GSTT1 showed no significant differences between cervical cancer patients and controls. In stratification analysis, significant elevated risk of all cases and SCC was associated with the NQO1 609TT genotype among nonsmokers (OR = 2.15, 95% CI = 1.08-4.30, P = 0.030; and OR = 2.83, 95% CI = 1.21-6.31, P = 0.011; respectively), but not smokers. No gene-gene interaction was observed in our case subjects. CONCLUSION: This is the first report that the NQO1 gene might be important in relation to the risk of squamous cell carcinoma of the cervix.

Lymphotoxin-alpha polymorphism and the risk of cervical cancer in Japanese subjects.

To examine the possible association between cervical cancer and Lymphotoxin-alpha (LT(alpha)) polymorphisms, C804A and A252G, an incident case-control study was conducted in Japanese. The cases were 131 cervical cancer patients. Controls were 320 healthy women. Risk estimation was conducted by an unconditional logistic model. Complete linkage disequilibrium was seen between LT(alpha) C804A and LT(alpha) A252G. We found that, compared with the 804CC genotype, 804CA and 804AA were associated with a decreased risk of cervical cancer (OR = 0.64, 95% CI = 0.40-1.02; and OR = 0.45, 95% CI = 0.21-0.95, respectively), especially of SCC (OR = 0.54, 95% CI = 0.32-0.91; and OR = 0.39, 95% CI = 0.16-0.92, respectively).

Impact of menstrual and reproductive factors on breast cancer risk in Japan: results of the JACC study.

The incidence of breast cancer among Japanese women, a traditionally low-risk population, has increased substantially. To evaluate the association of reproductive factors with breast cancer risk, we examined 38,159 Japanese women, aged 40-79 years, who responded to a questionnaire on reproductive and other lifestyle factors from 1988 to 1990 in the Japan Collaborative Cohort Study. During an average 7.6 years of follow-up, we documented 151 incidents of breast cancers. Cox proportional hazards modeling was employed to estimate relative risks (RR) and 95% confidence intervals (CI). There was a significant decline in the risk of breast cancer with increasing parity among parous women (trend P=0.01). Women with four or more parities had a 69% lower risk than uniparous women, a reduced risk was also evident among menopausal women. Breast cancer risk tended to rise with increasing age at first delivery (trend P=0.05), the association being very apparent among menopausal women (trend P=0.02). Compared to the women who had their first delivery before age 25, those who delayed this event until after age 34 had an RR of 2.12 (95% CI: 0.72-6.21) and 3.33 (1.07-10.3) among the overall subjects and the menopausal, respectively. There was no apparent association of breast cancer risk with age at menarche or menopause. Our study concerning reproductive risk factors suggests that breast cancer in Japan is similar to that in Western countries, and that reproductive factors, particularly the number of parity and age at first delivery, might be important in the etiology of breast cancer among Japanese women.

Precise definition of anonymization in genetic polymorphism studies.

Anonymization is an essential tool to protect privacy of participants in epidemiological studies. This paper classifies types of anonymization in genetic polymorphism studies, providing precise definitions. They are: 1) unlinkable anonymization at enrollment without a participant list; 2) unlinkable anonymization before genotyping with a participant list; 3) linkable anonymization; 4) unlinkable anonymization for outsiders; and 5) linkable anonymization for outsiders. The classification in view of accessibility to a table including genotype data with directly identifiable data such as names is important; if such tables exist, staff may obtain genotype information about participants. The first three modes are defined here as anonymization unaccessible to genotype data with directly identifiable information for research staff. Anonymization with a key code held by participants is possible with any of the above anonymization modes, by which participants can access to their own genotypes through telephone or internet. A guideline issued on March 29, 2001 with collaboration of three Ministries in Japan defines "anonymization in a linkable fashion" and "anonymization in an unlinkable fashion", "for the purpose of preventing the personal information from being divulged externally in violation of law, the present guidelines or a research protocol", but the contents are not clear in practice. The proposed definitions will be useful when we describe and discuss the preferable mode of anonymization for a given polymorphism study.

Genetic polymorphisms of p73 G4C14-to-A4T14 at exon 2 and p53 Arg72Pro and the risk of cervical cancer in Japanese.

To examine the possible association between cervical cancer and p73 G4C14-to-A4T14 in exon 2 and p53 Arg72Pro polymorphisms, an incident case-control study was conducted in Japanese. The cases were 112 cervical cancer patients. Controls were 320 healthy women and 122 non-cancer female outpatients. Risk estimation for each genotype by an unconditional logistic model demonstrated a possible association between the p73 A4T14 variant and the risk of cervical cancer in our Japanese population (OR = 1.57; 95%CI, 0.99-2.48, P = 0.053). There was no significant difference in the p53 Arg72Pro genotype frequency between the controls and cases.

Salvage treatment with docetaxel for recurrent epithelial ovarian cancer.

BACKGROUND: We investigated the clinical usefulness and toxicity of salvage treatment with docetaxel (70 mg/m2) infused at 3-week intervals in patients with recurrent ovarian cancer. METHODS: Retrospectively, we reviewed the clinical records of 24 patients diagnosed with recurrent ovarian cancer who had received the salvage treatment. RESULTS: A total of 128 courses (median, 5.5 courses; range, 2-8 courses) were administered to the 24 patients. The mean number of prior chemotherapy courses in the patients was 16.4 (range, 4-35 courses); they had already been treated heavily. The tumor response was evaluable at the end of the treatment in 20 patients, with the overall response rate being 15.0%. Using the criterion of serum carbohydrate antigen (CA)125 level, the response rate was 13.0%. By the time of the final docetaxel treatment, all 24 patients had relapsed and 19 had died of the disease. The median progression-free interval was 4.6 months (range, 1.3-7.8 months), and the median overall survival time was 13.7 months (range, 2.1-27.0 months). While hematological toxicity was not severe, 20.8% of patients experienced grade 3 asthenia/fatigue, and 5 patients refused further treatments with docetaxel because of this toxicity. CONCLUSIONS: Salvage treatment using docetaxel (70 mg/m2) was somewhat effective for recurrent ovarian cancer, although severe asthenia/fatigue was frequently observed. Docetaxel provides sufficient palliation of disease-related symptoms and some improvement in the length of life in patients with recurrent ovarian cancer, when asthenia/fatigue is mild.