Biomedical subjects

Ping Sun

Publications and source records attributed to Ping Sun.

At least 19 recordsLinked to original sources

PubMed2007

Reproductive risk factors for ovarian cancer in carriers of BRCA1 or BRCA2 mutations: a case-control study.

BACKGROUND: Several of the known risk factors for ovarian cancer are thought to act through their effects on ovulation and the menstrual cycle, such as parity, breastfeeding, and use of oral contraceptives. We aimed to assess the effect of these three risk factors, and of tubal ligation, on the risk of ovarian cancer in women who carry a mutation in the BRCA1 or BRCA2 genes. METHODS: We did a matched case-control study in women who were found to carry a pathogenetic mutation in BRCA1 or BRCA2. Participants were derived from a population-based study of ovarian cancer in Ontario, Canada, and from an international registry of mutation carriers based in Toronto, ON, Canada. All participants completed a written questionnaire that detailed their reproductive history. Women with invasive ovarian cancer and controls were matched on year of birth, country of residence, mutation (BRCA1 or BRCA2), and history of breast cancer. The odds ratios and 95% CI for ovarian cancer were estimated with respect to use of oral contraceptives, parity, breastfeeding, and tubal ligation. FINDINGS: Questionnaires were completed by 799 women with a history of invasive ovarian cancer (670 with BRCA1 mutations, 128 with BRCA2 mutations, and one with a mutation in both genes), and controls were 2424 women without ovarian cancer (2043 with BRCA1 mutations, 380 with BRCA2 mutations, and one with a mutation in both genes). Use of oral contraceptives reduced the risk of ovarian cancer in carriers of BRCA1 mutations (odds ratio 0.56 [95% CI 0.45-0.71]; p<0.0001) and carriers of BRCA2 mutations (0.39 [0.23-0.66]; p=0.0004). Parity was associated with a reduced risk for carriers of BRCA1 mutations (0.67 [0.46-0.96]; p=0.03), but with an increased risk for those with BRCA2 mutations (2.74 [1.18-6.41]; p=0.02). Breastfeeding was associated with a reduced risk for carriers of BRCA1 mutations (0.74 [0.56-0.97]; p=0.03). An effect of similar magnitude was seen for carriers of BRCA2 mutations (0.72 [0.41-1.29]; p=0.27), but this was not statistically significant. The association with tubal ligation was not significant for carriers of BRCA1 mutations (0.80 [0.59-1.08]; p=0.15), or for carriers of BRCA2 mutations (0.63 [0.34-1.15]; p=0.13). INTERPRETATION: Oral contraceptives could be used as a means to prevent ovarian cancer in carriers of BRCA1 and BRCA2 mutations. The possible adverse effect of parity on ovarian-cancer risk in women with a BRCA2 mutation needs further study.

Adult↗

PubMed2006

Fidelity of implementation in Project Towards No Drug Abuse (TND): a comparison of classroom teachers and program specialists.

This paper presents the results of an effectiveness trial of Project Towards No Drug Abuse [TND], in which we compared program delivery by regular classroom teachers and program specialists within the same high schools. Within 18 schools that were randomly assigned to the program or control conditions, health classrooms were assigned to program delivery by teachers or (outside) specialists. Classroom sessions were observed by pairs of observers to assess three domains of implementation fidelity: adherence, classroom process, and perceived student acceptance of the program. Pre- and immediate posttest survey data were collected from 2331 students. Of the four composite indexes of implementation fidelity that were examined, only one (quality of delivery) showed a difference between specialists and teachers, with marginally higher ratings of specialists (p < .10). Both teachers and program specialists achieved effects on three of the five immediate outcome measures, including program-specific knowledge, addiction concern, and social self-control. Students' posttest ratings of the program overall and the quality of program delivery failed to reveal differences between the teacher- and specialist-led classrooms. These results suggest that motivated, trained classroom teachers can implement evidence-based prevention programs with fidelity and achieve immediate effects.

Adult↗

PubMed2006

An insight into the mechanism of human cysteine dioxygenase. Key roles of the thioether-bonded tyrosine-cysteine cofactor.

Cysteine dioxygenase is a non-heme mononuclear iron metalloenzyme that catalyzes the oxidation of cysteine to cysteine sulfinic acid with addition of molecular dioxygen. This irreversible oxidative catabolism of cysteine initiates several important metabolic pathways related to diverse sulfurate compounds. Cysteine dioxygenase is therefore very important for maintaining the proper hepatic concentration of intracellular free cysteine. Mechanisms for mouse and rat cysteine dioxygenases have recently been reported based on their crystal structures in the absence of substrates, although there is still a lack of direct evidence. Here we report the first crystal structure of human cysteine dioxygenase in complex with its substrate L-cysteine to 2.7A, together with enzymatic activity and metal content assays of several single point mutants. Our results provide an insight into a new mechanism of cysteine thiol dioxygenation catalyzed by cysteine dioxygenase, which is tightly associated with a thioether-bonded tyrosine-cysteine cofactor involving Tyr-157 and Cys-93. This cross-linked protein-derived cofactor plays several key roles different from those in galactose oxidase. This report provides a new potential target for therapy of diseases related to human cysteine dioxygenase, including neurodegenerative and autoimmune diseases.

Amino Acid Sequence↗

PubMed2006

Atmospheric organochlorine pesticide concentrations near the Great Lakes: temporal and spatial trends.

As a part of the Integrated Atmospheric Deposition Network, atmospheric organochlorine pesticide concentrations were measured in both the gas and particle phases at seven sites near the Great Lakes. Much higher organochlorine pesticide concentrations were found in the gas phase compared to that in the particle phase. Long-term decreasing trends were observed for most pesticides in both phases. Two different seasonal trends were observed in the particle phase: (a) in-use pesticides, such as endosulfan, showed higher concentrations in the summer, a time corresponding to their agriculture use, and (b) restricted organochlorine pesticides, such as lindane, showed higher particle-phase concentrations in the winter, presumably due to their enhanced partitioning from the gas phase to particles. Generally, Chicago had the highest concentrations of chlordanes, dieldrin, and sigmaDDT, suggesting that urban areas could be sources of these compounds to atmosphere. Point Petre had the highest concentrations of endosulfan, likely due to its agricultural application in Southern Ontario.

Air Pollutants↗

PubMed2006

Trends in polycyclic aromatic hydrocarbon concentrations in the great lakes atmosphere.

Atmospheric polycyclic aromatic hydrocarbon (PAHs) concentrations were measured in both the vapor and particle phases at seven sites near the Great Lakes as a part of the Integrated Atmospheric Deposition Network. Lower molecular weight PAHs, including fluorene, phenanthrene, fluoranthrene, and pyrene, were dominant in the vapor phase, and higher molecular weight PAHs, including chrysene, benzo[a]pyrene, and coronene, were dominant in the particle phase. The highest PAH concentrations in both the vapor and particle phases were observed in Chicago followed by the semiurban site at Sturgeon Point, NY. The spatial difference of PAH concentrations can be explained by the local population density. Long-term decreasing trends of most PAH concentrations were observed in both the vapor and particle phases at Chicago, with half-lives ranging from 3-10 years in the vapor phase and 5-15 years in the particle phase. At Eagle Harbor, Sleeping Bear Dunes, and Sturgeon Point, total PAH concentrations in the vapor phase showed significant, but slow, long-term decreasing trends. At the Sturgeon Point site, which was impacted by a nearby city, particle-phase PAH concentrations also declined. However, most particle-phase PAH concentrations did not show significant long-term decreasing trends at the remote sites. Seasonal trends were also observed for particle-phase PAH concentrations, which were higher in the winter and lower in the summer.

Air Pollutants↗

PubMed2006

Socio-demographic and cultural comparison of overweight and obesity risk and prevalence in adolescents in Southern California and Wuhan, China.

PURPOSE: This study performed parallel analyses on two large samples of seventh graders living in Los Angeles, California and in Wuhan, China to make direct comparisons of overweight and obesity risks in Western and Eastern cultural environments. METHODS: Two representative samples of 1772 and 1896 seventh grade students were randomly selected from the public or parochial middle schools in the greater Los Angeles area of Southern California in the United States, and public schools in Wuhan city of China. Two body mass index (BMI) references recently established by the U.S. National Center for Health Statistics (NCHS) and the International Obesity Task Force (IOTF), respectively, were used to define overweight (85th < or = BMI < 95th percentile) and obesity (BMI > or = 95th percentile). Logistic regressions were conducted to examine relationships between socioeconomic status (SES) and obesity risk. RESULTS: The prevalence rates of combined overweight and obesity in Los Angeles and in Wuhan were 43.1% and 12.1%, respectively, by the US-NCHS reference, and 45.8% and 11.9%, respectively, by the IOTF reference. Chinese-American adolescents had higher prevalence rates for overweight and obesity than those from China. SES was positively related to the risk of overweight and obesity in the Chinese sample, whereas a negative association was found in Southern California adolescents. Urbanicity was significantly positively related to higher overweight and obesity prevalence. CONCLUSION: Different overweight and obesity prevalence estimates and SES effects were observed for American and Chinese adolescent samples. Research on the underlying mechanisms is needed to help us to set up a tailored program for obesity prevention in Eastern and Western cultural environments.

Adolescent↗

PubMed2006

Tobacco use among youth and adults in Mainland China: the China Seven Cities Study.

OBJECTIVE: The China Seven Cities Study (CSCS) monitors geographic and temporal trends in tobacco use among adolescents and adults in seven cities throughout Mainland China: Harbin, Shenyang, Wuhan, Chengdu, Kunming, Hangzhou, and Qingdao. This article presents the methodology and prevalence data from the baseline survey of the CSCS, conducted in 2002. METHODS: Stratified random samples of middle schools, high schools, and colleges were selected within each city. Students and their parents completed self-report surveys of their tobacco use. Data were obtained from 6138 middle school students, 5848 academic high school students, 2448 vocational high school students, 2556 college students, and 25 697 parents. RESULTS: Smoking prevalence varied across age groups, school types, genders, and cities. Past-month smoking prevalence was 9% among middle school students, 8% among academic high school students, 26% among vocational high school students, 21% among college students, and 40% among parents. Smoking prevalence was higher among males than among females, with larger gender disparities among adults than among youth. Smoking also varied across cities, with higher smoking prevalence in southwestern cities and lower prevalence in coastal cities. Intraclass correlations of students within schools are presented to inform statistical power estimates for further research in China. CONCLUSIONS: These results provide a baseline for future longitudinal studies of smoking in these cities and identify demographic groups at risk for tobacco-related disease. Effective smoking prevention programmes for youth and smoking cessation programmes for adults are needed in China, especially in the lower-income southwestern cities and in vocational high schools throughout the country.

Adolescent↗

PubMed2006

The risk of endometrial cancer in women with BRCA1 and BRCA2 mutations. A prospective study.

OBJECTIVE: To evaluate the risk of endometrial cancer in women who carry a deleterious mutation in the BRCA1 or BRCA2 genes. PATIENTS AND METHODS: Women known to carry a BRCA1 or BRCA2 mutation, aged 45 to 70, were identified from an international registry and were followed prospectively. A total of 857 women completed a baseline questionnaire and one or more follow-up questionnaires. Study subjects were followed until diagnosis of endometrial cancer, ovarian cancer, death or the date of completion of the last questionnaire. The expected number of endometrial cancers was calculated using age and country-specific incidence rates. RESULTS: After an average follow-up period of 3.3 years, six women were diagnosed with endometrial cancer, compared to 1.13 cancers expected (SIR=5.3, p=0.0011). Four of these six patients used tamoxifen in the past. The risk among women who were never exposed to tamoxifen treatment was not significantly elevated (SIR=2.7, p=0.17), but among the 226 participants who had used tamoxifen (220 as treatment and six for the primary prevention of breast cancer) the relative risk for endometrial cancer was 11.6 (p=0.0004). CONCLUSION: The main contributor to the increased risk of endometrial cancer among BRCA carriers is tamoxifen treatment for a previous breast cancer. The risk and benefits of prophylactic hysterectomy should be discussed with women with a BRCA mutation considering tamoxifen therapy.

Adult↗

PubMed2006

Familial risks of esophageal cancer among the Turkmen population of the Caspian littoral of Iran.

In northeastern Iran, there is an area of high incidence of esophageal cancer, which is populated by residents of Turkmen ancestry. Several environmental risk factors for esophageal cancer have been proposed, but the roles of familial and genetic factors have not been studied extensively in the Turkmen population. We evaluated the importance of familial risk factors for esophageal cancer by performing a case-control study of 167 cases of esophageal squamous cell carcinoma and 200 controls of Turkmen ethnicity. Detailed family pedigrees of the cases and controls were constructed, which documented all cancers in first- and second-degree relatives. The actuarial risk of cancer was then estimated in 2,097 first-degree relatives of cases and 2,783 first-degree relatives of the controls. A hazard ratio was constructed, based on a comparison of the 2 cumulative incidence curves. The risk to age 75 of esophageal cancer in the first-degree relatives of Turkmen patients with esophageal cancer was 34% versus 14% for the first-degree relatives of the controls (hazard ratio = 2.3; p = 3 x 10(-8)). Cases (9.6%) reported that their parents were related, versus 2.5% of the controls who reported this. (odds ratio = 4.1; p value = 0.006). Familial factors are important in the etiology of esophageal cancer among the Turkmen residents of Iran. The hazard ratio of 2.3 for cancer among first-degree relatives is consistent with an important contribution of heritable factors. It will be of interest to perform marker studies to establish which genes are responsible.

Actuarial Analysis↗

PubMed2006

Taxonomic characterization of two marine peritrichous ciliates, Epicarchesium corlissi n. sp. and Pseudovorticella jiangi n. sp. (Ciliophora: Peritrichia), from northern China.

Two new marine peritrich ciliates, Epicarchesium corlissi n. sp. and Pseudovorticella jiangi n. sp., were discovered in mariculture waters on the coast of northern China near Qingdao. Their morphology, infraciliature and silverline system were investigated based on both living and silver-impregnated specimens. E. corlissi is characterized as follows: marine Epicarchesium with dichotomously branched stalk; zooids elongate, approximately 60-70 x 25-35 microm in vivo; peristomial collar double-folded; macronucleus J-shaped; single, small contractile vacuole ventrally positioned; more than 60 striations between peristome and aboral trochal band, 13-18 from aboral trochal band to scopula; abstomal end of row 1 of infundibular polykinety 3 terminating at same level as rows 2 and 3 of infundibular polykinety 3; rows 2 and 3 of infundibular polykinety 3 much longer than row 1 and converging adstomally with infundibular polykinety 1. The new species P. jiangi is diagnosed as follows: marine Pseudovorticella; zooid inverted bell-shaped, approximately 80x60 microm in vivo and with a broad, flat, thin peristomial collar that measures approximately 90 microm across; pellicle with transparent cortical vesicles; macronucleus J-shaped; number of silverlines between peristome and aboral trochal band 20-24, from aboral trochal band to scopula 9-11; abstomal end of row 1 of infundibular polykinety 3 diverges from the other two rows of this polykinety and ends alongside row 3 of infundibular polykinety 2.

Animals↗

PubMed2006

Utility of the theory of reasoned action and theory of planned behavior for predicting Chinese adolescent smoking.

One third of smokers worldwide live in China. Identifying predictors of smoking is important for prevention program development. This study explored whether the Theory of Reasoned Action (TRA) and Theory of Planned Behavior (TPB) predict adolescent smoking in China. Data were obtained from 14,434 middle and high school students (48.6% boys, 51.4% girls) in seven geographically varied cities in China. TRA and TPB were tested by multilevel mediation modeling, and compared by multilevel analyses and likelihood ratio tests. Perceived behavioral control was tested as a main effect in TPB and a moderation effect in TRA. The mediation effects of smoking intention were supported in both models (p<0.001). TPB accounted for significantly more variance than TRA (p<0.001). Perceived behavioral control significantly interacted with attitudes and social norms in TRA (p<0.001). Therefore, TRA and TPB are applicable to China to predict adolescent smoking. TPB is superior to TRA for the prediction and TRA can better predict smoking among students with lower than higher perceived behavioral control.

Adolescent↗

PubMed2006

Salpingo-oophorectomy and the risk of ovarian, fallopian tube, and peritoneal cancers in women with a BRCA1 or BRCA2 Mutation.

CONTEXT: Women with BRCA1 or BRCA2 mutation are often advised to undergo preventive oophorectomy. The effectiveness of this intervention has not been prospectively evaluated in a large cohort. OBJECTIVES: To estimate the incidence of ovarian, fallopian tube, and primary peritoneal cancer in women who carry a deleterious mutation in BRCA1 or BRCA2. To estimate the reduction in risk of these cancers associated with a bilateral prophylactic salpingo-oophorectomy. DESIGN, SETTING, AND PARTICIPANTS: Women known to carry a BRCA1 or BRCA2 mutation were identified from an international registry between 1992 and 2003. A total of 1828 carriers at 1 of 32 centers in Canada, the United States, Europe, and Israel completed questionnaires at baseline and follow-up. Participants were observed from the date of study entry until: diagnosis of ovarian, fallopian tube, or peritoneal cancer; death; or the date of the most recent follow-up. INTERVENTION: Participants were divided into women who had undergone bilateral prophylactic oophorectomy and those who had not. MAIN OUTCOME MEASURE: The incidence of ovarian, peritoneal, and fallopian tube cancer was determined by survival analysis. The risk reduction associated with prophylactic salpingo-oophorectomy was evaluated by a time-dependent survival analysis, adjusting for covariates. RESULTS: After a mean follow-up of 3.5 years, 50 incident ovarian, fallopian tube, and peritoneal cancer cases were reported in the cohort. Of the 1828 women, 555 (30%) underwent a bilateral prophylactic salpingo-oophorectomy prior to study entry, 490 (27%) underwent the procedure after entering the study, and 783 (43%) did not undergo the procedure. There were 32 incident cancers diagnosed in women with intact ovaries (1015/100,000 per year). Eleven cancer cases were identified at the time of prophylactic oophorectomy and 7 were diagnosed following prophylactic oophorectomy (217/100,000 per year). The estimated cumulative incidence of peritoneal cancer is 4.3% at 20 years after oophorectomy. The overall (adjusted) reduction in cancer risk associated with bilateral oophorectomy is 80% (multivariate hazard ratio = 0.20; 95% confidence interval, 0.07-0.58; P = .003). CONCLUSION: Oophorectomy is associated with reduced risk of ovarian and fallopian tube cancer in high-risk women, although there is a substantial residual risk for peritoneal cancer in BRCA1 and BRCA2 mutation carriers following prophylactic salpingo-oophorectomy.

Adult↗

PubMed2006

Age-related smoking progression among adolescents in China.

PURPOSE: This study examined the differences in smoking progression between middle and upper school students. METHODS: The China Seven Cities Study (CSCS) is a longitudinal cohort study. The current sample consists of subjects with both baseline and one-year follow-up measures collected between October 2002 and December 2003. There were 4842 students from 62 middle schools and 5806 students from 83 upper schools. Multilevel random-coefficient modeling techniques were applied. RESULTS: Among male never or lifetime ever smokers, middle school students were susceptible to transitioning more rapidly than upper school students (never--RR: 1.272, 95% confidence interval [CI]: .985-1.642; lifetime ever--RR: 1.497, 95% CI: .979-2.290). Among female lifetime ever smokers, middle school students were more likely to progress than upper school students (RR: 1.353, 95% CI: 1.038-1.763). CONCLUSION: This longitudinal study is the first to explore differences in smoking progression among adolescents in China. The results revealed that over a one-year interval, there was greater progression across smoking trajectories during early adolescence (corresponding to middle school) than later adolescence (upper school). This is consistent with the neurological development hypothesis, but does not rule out alternative explanations. These findings are important to consider relative to the content and timing of prevention interventions in China where smoking rates approach 70% in adult males and are increasing rapidly in women.

Adolescent↗

PubMed2006

Sonolytic reactions of phenanthrene in organic extraction solutions.

Ultrasonic extraction is a common method used to extract semi-volatile and nonvolatile organic compounds such as polycyclic aromatic hydrocarbons (PAHs) from solid matrices. However, ultrasonic energy has been suspected to lead to undesired reactions of the solute and thus affect qualitative and quantitative results. In this paper, sonolytic reactions of phenanthrene in common organic extraction solutions were examined using a 20kHz ultrasonic probe under conditions commonly used for ultrasonic extraction. Extraction parameters including phenanthrene concentration, solvent type, pulse length, and sonication time were investigated. Hexane:acetone (1:1 V/V) resulted in less phenanthrene degradation than dichloromethane (DCM):acetone (1:1 V/V). Initial solute concentration, length of sonication time, and solvent type affected the degradation of phenanthrene. Reaction byproducts including methylphenanthrene and methylnaphthalene detected after sonication indicate that phenanthrene reacts by both direct pyrolysis and reaction with methyl or ethyl radicals formed from solvent pyrolysis.

Organic Chemicals↗

PubMed2006

Ganglioside GM3 promotes carcinoma cell proliferation via urokinase plasminogen activator-induced extracellular signal-regulated kinase-independent p70S6 kinase signaling.

Overexpression of NeuAcalpha2-3Galbeta1-4Glcbeta1-Cer (GM3), a major ganglioside of cutaneous tumor cell membranes, inhibits ligand-dependent and ligand-independent activation of the epidermal growth factor (EGF) receptor in normal and neoplastic epithelial cells. This leads to the suppression of Ras/extracellular signal-regulated kinase (ERK) activation and, in the presence of EGF or fibronectin, inhibits cell proliferation. However, some tumor cells show increased levels of GM3, and vaccines that target GM3 can inhibit the growth of neoplastic cells in vivo, especially melanomas. We report that in the presence of urokinase plasminogen activator (uPA), overexpression of GM3 paradoxically increases the proliferation of carcinoma cells by augmenting ERK-independent p70S6 kinase activation. Functional blockade of uPA receptor (uPAR) or inhibition of p70S6 kinase, but not inhibition of Ras/ERK signaling, suppresses this GM3-induced stimulation of cell proliferation. The ERK-independent activation of p70S6 kinase involves phosphorylation at threonine-389, threonine-421/serine-424, and serine-411 sites with intermediate phosphatidylinositol 3 kinase and protein kinase C-zeta activation. These studies implicate gangliosides as enhancers of uPAR-related signaling and suggest that the response to GM3 depends on the local concentration of uPA. Therapeutic modalities that target or supplement gangliosides may require concomitant treatment that suppresses EGFR or uPAR signaling, respectively, to control neoplastic cell proliferation.

Carcinoma, Squamous Cell↗

PubMed2006

Short-term effects of Project EX-4: a classroom-based smoking prevention and cessation intervention program.

OBJECTIVE: Researchers continue to try to develop effective teen tobacco use prevention and cessation programs. Three previous school clinic-based studies established the efficacy of Project EX for teen smoking cessation. This fourth study adapts Project EX to the classroom context. This paper reports the findings based on pretest and posttest surveys conducted immediately prior and post-intervention. METHODS: An eight-session classroom-based curriculum was developed and tested with a randomized controlled trial that involved a total of 1097 students in six program and six control continuation high schools. Program-specific knowledge and smoking measures were assessed at both the pretest and posttest surveys, and were used to evaluate the program's effect on the immediate outcomes. The immediate outcomes effects were analyzed with multi-level random coefficients models. RESULTS: Program students provided favorable process ratings of the overall program and each session. Compared with the students in the control condition, students in the program condition showed a greater change in correct knowledge responses from pretest to posttest (beta=+5.5%, p=0.0003). Students in the program condition also experienced a greater reduction in weekly smoking (beta=-6.9%, p=0.038), and intention for smoking in the next 12 months (beta=-0.21 in 5-level scale, p=0.023). CONCLUSIONS: EX-4 immediate outcome results revealed favorable student responses to the program, increases in knowledge, and decreases in smoking relative to a standard care control condition.

Adolescent↗

PubMed2006

Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers: an update.

Women with a mutation in BRCA1 or BRCA2 face a lifetime risk of breast cancer of approximately 80%, and following the first diagnosis the 10-year risk of contralateral breast cancer is approximately 30%. It has been shown that both tamoxifen and oophorectomy prevent contralateral breast cancer, but it is not clear whether there is a benefit in giving tamoxifen to women who have previously undergone an oophorectomy. Furthermore, the relative degree of protection in BRCA1 and BRCA2 carriers has not been well evaluated. We studied 285 women with bilateral breast cancer and a BRCA1 or BRCA2 mutation, and 751 control women with unilateral breast cancer and a BRCA1 or BRCA2 mutation in a matched case-control study. Control women were of similar age and had a similar age of diagnosis of breast cancer and had been followed for as long as the case for a second primary breast cancer. The history of tamoxifen use for treating the first breast cancer was compared between bilateral and unilateral cases. The multivariate odds ratio for contralateral breast cancer associated with tamoxifen use was 0.50 for carriers of BRCA1 mutations (95% CI, 0.30-0.85) and was 0.42 for carriers of BRCA2 mutations (95% CI, 0.17-1.02). The protective effect of tamoxifen was not seen among women who had undergone an oophorectomy (OR = 0.83; 95%CI, 0.24-2.89) but this subgroup was small. In contrast, a strong protective effect of tamoxifen was apparent among women who were premenopausal or who had undergone natural menopause (OR = 0.44; 95% CI, 0.27-0.65).

Adult↗

PubMed2006

Association of PINK1 and DJ-1 confers digenic inheritance of early-onset Parkinson's disease.

Mutations in genes encoding both DJ-1 and pten-induced kinase 1 (PINK1) are independently linked to autosomal recessive early-onset familial forms of Parkinson's disease (PD). We here report identification of a family with PD patients harboring novel heterozygous missense mutations in both PINK1 and DJ-1 genes encoding DJ-1A39S and PINK1P399L, respectively. In transfected cells, DJ-1 interacts with PINK1. PINK1P399L is less stable than the wild-type protein and is degraded via the ubiquitin-mediated proteasomal pathway. Expression of wild-type DJ-1 increased steady-state levels of PINK1, whereas expression of DJ-1A39S reduced steady-state levels of PINK1. Furthermore, co-expression of wild-type DJ-1 and PINK1 suppresses neurotoxin 1-methyl-4-phenylpyridinium (MPP(+))-induced death of dopaminergic SH-SY5Y cells. In contrast, co-expression of PD-associated DJ-1A39S and PINK1P399L significantly potentiated susceptibility of SH-SY5Y cells to MPP(+)-induced cell death. This study reports the first case of autosomal recessive PD with digenic inheritance and demonstrates that DJ-1 and PINK1 physically associate and collaborate to protect cells against stress via complex formation.

Adult↗