A Genetic Epidemiological Study of Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma (NPC) is a malignant tumor arising from the epithelial lining of the nasopharynx. It is rare in most parts of the world, but much more common in South East Asia, North Africa and in the Arctic Circle of North America. Among individuals less than 65 years of age, it is the third most prevalent cancer type in Hong Kong, and the second most prevalent in Singapore Chinese. Since the disease mostly affects males in their 40s, the occurrence of nasopharyngeal carcinoma has a strong social impact in endemic areas. NPC is a complex disease with both environmental and genetic factors playing a role in its development. Suggested risk factors include tobacco, salted fish, domestic fumes, occupational dust and heat, herbal medicine, Epstein-Barr virus (EBV) activation, and a familial history of NPC. In this thesis, environmental and genetic factors in the etiology of nasopharyngeal carcinoma are addressed

Breast cancer risk prediction using a polygenic risk score in the familial setting: a prospective study from the Breast Cancer Family Registry and kConFab.

PURPOSE: This study examined the utility of sets of single-nucleotide polymorphisms (SNPs) in familial but non-BRCA-associated breast cancer (BC). METHODS: We derived a polygenic risk score (PRS) based on 24 known BC risk SNPs for 4,365 women from the Breast Cancer Family Registry and Kathleen Cuningham Consortium Foundation for Research into Familial Breast Cancer familial BC cohorts. We compared scores for women based on cancer status at baseline; 2,599 women unaffected at enrollment were followed-up for an average of 7.4 years. Cox proportional hazards regression was used to analyze the association of PRS with BC risk. The BOADICEA risk prediction algorithm was used to measure risk based on family history alone. RESULTS: The mean PRS at baseline was 2.25 (SD, 0.35) for affected women and was 2.17 (SD, 0.35) for unaffected women from combined cohorts (P < 10-6). During follow-up, 205 BC cases occurred. The hazard ratios for continuous PRS (per SD) and upper versus lower quintiles were 1.38 (95% confidence interval: 1.22-1.56) and 3.18 (95% confidence interval: 1.84-5.23) respectively. Based on their PRS-based predicted risk, management for up to 23% of women could be altered. CONCLUSION: Including BC-associated SNPs in risk assessment can provide more accurate risk prediction than family history alone and can influence recommendations for cancer screening and prevention modalities for high-risk women.Genet Med 19 1, 30-35.National Institutes of HealthThis is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/gim.2016.4

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A&gt;T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

A likelihood ratio approach for utilizing case-control data in the clinical classification of rare sequence variants:Application to BRCA1 and BRCA2

A large number of variants identified through clinical genetic testing in disease susceptibility genes are of uncertain significance (VUS). Following the recommendations of the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP), the frequency in case-control datasets (PS4 criterion) can inform their interpretation. We present a novel case-control likelihood ratio-based method that incorporates gene-specific age-related penetrance. We demonstrate the utility of this method in the analysis of simulated and real datasets. In the analysis of simulated data, the likelihood ratio method was more powerful compared to other methods. Likelihood ratios were calculated for a case-control dataset of BRCA1 and BRCA2 variants from the Breast Cancer Association Consortium (BCAC) and compared with logistic regression results. A larger number of variants reached evidence in favor of pathogenicity, and a substantial number of variants had evidence against pathogenicity findings that would not have been reached using other case-control analysis methods. Our novel method provides greater power to classify rare variants compared with classical case-control methods. As an initiative from the ENIGMA Analytical Working Group, we provide user-friendly scripts and preformatted Excel calculators for implementation of the method for rare variants in BRCA1, BRCA2, and other high-risk genes with known penetrance.</p

Impact of On-Board Hybrid Energy Storage Devices on Energy-Saving Operation for Electric Trains in DC Railway Systems

To improve the energy-efficiency of transport systems, it is necessary to investigate electric trains with on-board hybrid energy storage devices (HESDs), which are applied to assist the traction and recover the regenerative energy. In this paper, a time-based mixed-integer linear programming (MILP) model is proposed to obtain the energy-saving operation for electric trains with different constraints of on-board HESDs, such as their capacity, initial state of charge (SOC), and level of degradation. The proposed integrated power flow model based on the train longitudinal dynamics, power split of on-board HESDs, and line impedance is discretized and linearized, aiming to minimize the net energy consumption (NEC). The results reveal that on-board HESDs with a higher capacity does not necessarily lead to a higher energy-saving rate; a lower or excessive initial SOC could undermine the energy-saving potential; considering the long-term train operation, the degradation of the Li-ion battery will influence the energy-saving operation for electric trains, as well as result in an energy-saving rate that ranges from 41.57% to 31.90%. The practical data from Guangzhou Metro Line 7 were applied in the simulations, which enhanced the practicality and effectiveness of the proposed method

Does Short-Term Combined Irrigation Using Brackish-Reclaimed Water Cause the Risk of Soil Secondary Salinization?

Brackish water has to be used to irrigate crops for harvest due to the scarcity of freshwater resources. However, brackish water irrigation may cause secondary soil salinization. Whether the combined utilization of different non-conventional water resources could relieve the risk of secondary soil salinization has not been reported. In order to explore the safe and rational utilization of brackish water in areas where freshwater resources are scarce, a pot experiment was conducted to study the risk of secondary soil mixed irrigation and rotational irrigation using brackish water and reclaimed water or freshwater. The results indicated that: (1) Short-term irrigation using reclaimed water did not cause secondary soil salinization, although increasing soil pH value, ESP, and SAR. The indices did not exceed the threshold of soil salinization. (2) Compared with mixed irrigation using brackish–freshwater, the contents of soil exchangeable Ca2+, K+, and Mg2+ increased, and the content of soil exchangeable Na+ decreased under rotational irrigation using brackish-reclaimed water. In addition, the contents of soil exchangeable Na+ and Mg2+ under mixed irrigation or rotational irrigation were significantly lower, and the exchangeable K+ content of the soil was higher compared with brackish water irrigation. The exchangeable Ca2+ content under rotational irrigation was higher than that of brackish water irrigation, while the reverse was seen under mixed irrigation. (3) For different combined utilization modes of brackish water and reclaimed water, the ESP and SAR were the lowest under rotational irrigation, followed by mixed irrigation and brackish water irrigation. The ESP under brackish water treatment exceeded 15%, indicating a certain risk of salinization, while ESPs under other treatments were below 15%. Under mixed irrigation or rational irrigation using reclaimed-brackish water, the higher the proportion or rotational times of reclaimed water, the lower the risk of secondary soil salinization. Therefore, short-term combined irrigation using brackish water and reclaimed water will not cause the risk of secondary soil salinization, but further experiments need to verify or cooperate with other agronomic measures in long-term utilization

Response of Soil Microenvironment and Crop Growth to Cyclic Irrigation Using Reclaimed Water and Brackish Water

The scarcity of freshwater resources has increased the use of nonconventional water resources such as brackish water, reclaimed water, etc., especially in water-scarce areas. Whether an irrigation cycle using reclaimed water and brackish water (RBCI) poses a risk of secondary soil salinization to crop yields needs to be studied. Aiming to find an appropriate use for different nonconventional water resources, pot experiments were conducted to study the effects of RBCI on soil microenvironments, growth, physiological characteristics and antioxidation properties of crops. The results showed the following: (1) compared to FBCI, the soil moisture content was slightly higher, without a significant difference, while the soil EC, sodium and chloride ions contents increased significantly under the RBCI treatment. With an increase in the reclaimed water irrigation frequency (Tri), the contents of EC, Na+ and Cl− in the soil decreased gradually, and the difference was significant; the soil moisture content also decreased gradually. (2) There were different effects of the RBCI regime on the soil’s enzyme activities. With an increase in the Tri, the soil urease activity indicated a significant upward trend as a whole. (3) RBCI can alleviate the risk of soil salinization to some extent. The soil pH values were all below 8.5, and were without a risk of secondary soil alkalization. The ESP did not exceed 15 percent, and there was no possible risk of soil alkalization except that the ESP in soil irrigated by brackish water irrigation went beyond the limit of 15 percent. (4) Compared with FBCI, no obvious changes appeared to the aboveground and underground biomasses under the RBCI treatment. The RBCI treatment was conducive to increasing the aboveground biomass compared with pure brackish water irrigation. Therefore, short-term RBCI helps to reduce the risk of soil salinization without significantly affecting crop yield, and the irrigation cycle using reclaimed-reclaimed-brackish water at 3 g·L−1 was recommended, according to the experimental results

Risk of Secondary Soil Salinization under Mixed Irrigation Using Brackish Water and Reclaimed Water

The use of unconventional water resources is an effective way to alleviate the scarcity of freshwater resources, especially in areas where freshwater is scarce, but reclaimed water is abundant. To explore the reasonable utilization of brackish water and reclaimed water, a pot experiment was carried out to study the risk of secondary soil salinization. The experiment set two salinity levels of brackish water, four mixed irrigation ratios of brackish water and reclaimed water, and freshwater irrigation as the control. The results showed that: (1) Soil moisture content, salt content, pH, ESP, and SAR decreased with the increase in the proportion of reclaimed water in the mixture. (2) Soil exchangeable Ca2+ content under mixed irrigation was higher than that of brackish water irrigation and reclaimed water irrigation. The content was especially significantly higher under the 1:2 mixed irrigation with brackish-reclaimed water. With the increase of the proportion of reclaimed water in the mixture, soil exchangeable Na+ content decreased, and a significant difference was found between treatments. The soil exchangeable K+ decreased at first and then increased, while the soil exchangeable Ca2+ increased at first and then decreased. The trend of the change of soil exchangeable Mg2+ content was similar to that of soil exchangeable Ca2+ content. (3) Based on the soil pH value, there was no risk of soil alkalization in all treatments. Based on ESP, ESP was less than 15% under freshwater irrigation, brackish (3 g/L)-reclaimed water 1:2 mixed irrigation, and reclaimed water irrigation, indicating no risk of alkalization. However, other treatments may cause soil alkalization. (4) At 3 g/L of brackish water, there was a salinization risk when the proportion of reclaimed water in the mixture was less than 1/2, but there was no salinization risk when the proportion was greater than 1/2. At 5 g/L of brackish water, there was a salinization risk under mixed irrigation. Therefore, the mixed irrigation of brackish water and reclaimed water had the risk of secondary soil salinization, and the appropriate salinity and mixing ratio should be selected

Location of study sites.

<p>▪, eelgrass transplantation zone in Huiquan Bay; •, natural intertidal eelgrass bed in Qingdao Bay.</p