Small scale effects on the mechanical behaviors of protein microtubules based on the nonlocal elasticity theory.

Based on the nonlocal elastic theory, small scale effects are considered in the investigation of the mechanical properties of protein microtubules. A new prediction formula for the persistence lengths of microtubules with the consideration of the small scale effect is presented. Subsequently, the buckling of microtubules is studied based on a nonlocal elastic beam model. The predicted results of our model indicate that the length-dependence of persistence length is related not only to the shear terms, but also to the small scale effect. The Eular beam model, which is always considered unable to explain the length-dependence of microtubules, can capture the length-dependence of the persistence length of microtubules with the consideration of the small scale effect. The elastic buckling behaviors of microtubules in viscoelastic surrounding cytoplasm are also considered using the nonlocal Timoshenko beam model in this paper, and the results indicate that the small scale effect of microtubules also plays an important role in the buckling of microtubules.

[Relationship between estrogen-biosynthesis gene (CYP17, CYP19, HSD17beta1) polymorphisms and breast cancer].

OBJECTIVE: To explore the relationship between the polymorphism of estrogen-biosynthesis genes (CYP17, CYP19, HSD17beta1) and risk of breast cancer. METHODS: A matched case-control study was designed. From May 2007 to July 2008, 200 pairs of subjects with and without breast cancer were enrolled, who were matched by age and menstruation status. Demographical characteristics, dietary factors and reproductive factors were investigated by questionnaire. CYP17 locus 1931 (T-->C), CYP19 codon 264 (Arg-->Cys) and HSD17beta1 locus 1954 (A-->G) were identified by AS-PCR (allele-specific PCR). The gene-gene interaction were analyzed with the MDR model (multifactor dimensionality reduction). Based on the results of MDR model, an unconditional logistic regression model was simulated to estimate the ORs of interaction factors and other risk factors. RESULTS: The main effect of CYP17, CYP19 and HSD17beta1 susceptible genotypes were not correlated to breast cancer (OR approximately 1, P > 0.05). The positive interaction effect between CYP17 (T 1931C) and HSD17beta1 (A1954G) was discovered by MDR model with a statistically significant difference (Sign test, P = 0.05). The model's testing balance accuracy was 56.00%, and crossing validation consistency was 10/10. Multivariable unconditional logistic regression showed that after adjusting BMI, intake of estrogen, age of first birth, number of abortion and period of breast feeding, the interaction item of CYP17 (T1931C) and HSD17beta1 (A1954G) was strongly and positively correlated to breast cancer (OR = 2.52, 95%CI = 1.54 to 4.11). CONCLUSION: The estrogen-biosynthesis genes CYP17 (T1931C) and HSD17beta1 (A1954G) polymorphism may jointly increase the risk of breast cancer.

[Using MSR model to analyze the impact of gene-gene interaction with related to the genetic polymorphism of metabolism enzymes on the risk of breast cancer].

OBJECTIVE: To identify the interactions of susceptive genes with related to the genetic polymorphism of metabolism enzymes (CYP1A1, GSTT1 and GSTM1) and their impacts on the risk of breast cancer; and to test the feasibility of using Multifactor Dimensionality Reduction (MDR) model in analyzing gene-gene interactions. METHODS: A paired case-control study, matched by age and menstruate state, was conducted. From December 2003 to September 2004, 78 pairs of people with and without breast cancers were investigated. The variant genotypes of CYP1A1 Msp I and GSTT1/M1 were identified by PCR-RFLP and multiplex PCR assays. The gene-gene interactions were analyzed with the MDR model. Based on the result of the MDR model, a conditional logistic regression model was constructed as the final cause-effect interpretative model. RESULTS: The interaction between CYP1A1 Msp I variant genotype (vv) and GSTT1 null genotype gave the best MDR model with statistical significance (Sign Test, P = 0.05). The model Testing Balance Accuracy was 0. 5920. The Cross-Validation consistency was 10/10. The final conditional logistic regression based on the MDR model showed that passive smoking, abortion and gene-gene interaction were risks of breast cancers, with an OR (95% confidence interval) of 12.234 (1.7459-85.7279), 4.554 (1.3250-15.6507) and 9.597 (1.5783-58.3599), respectively. CONCLUSION: The MDR model may be an effective method for estimating risks of breast cancers due to gene-gene and gene-environment interactions. The gene-gene interaction with related to the genetic polymorphism of metabolism enzymes (CYP1A1 and GSTT1) may increase the risk of breast cancer by disturbing the metabolism of estrogen.

[Study on the relationship between organochlorine pesticides and level of residues in serum and daily foodstuff].

OBJECTIVE: To study the contents of organochlorine pesticides in human bodies and residues in serum of populations with non-occupational exposure as well as to study the relationship between organochlorine pesticides in foodstuff and residues levels in serum. METHODS: A cross-section study was conducted. 107 men and 142 women who were all healthy and living in the communities were investigated from Mar. 2004 to Jul. 2004. Level of daily food exposure was estimated through questionnaires while DDTs and HCHs serum levels were detected by EC-ECD. The relationship between organochlorine pesticides contents in foods and residues in serum were analyzed by ridge regression. RESULTS: Fresh fish was positively correlated to men's serum level of beta-HCH and p,p'-DDT (beta = 0.1266 and beta = 0.0595) while vegetables and fruits were negatively correlated to women's serum level of beta-HCH (beta = -0.1066). Soybean was negatively correlated to women's serum level of p,p'-DDE and p,p'-DDT (beta = -0.0965 and 3 = -0.0581). Alcohol consumption was negatively correlated to men's serum level of beta-HCH and p,p'-DDE and women's serum level of p,p'-DDE (beta = -0.1315, beta = -0.1599 and P = -0.1128).Salted meat was negatively correlated to men's serum level of beta-HCH and p, p'-DDT (P = -0. 066 and P = - 0.0569). CONCLUSION: In this study, fresh fish might increase the body burden of organochlorine pesticides and residues while alcohol might promote the excretion of organochlorine pesticides. Pickled meat and vegetal foodstuff might contain low-level of organochlorine pesticides and residues.

[Serum organochlorines pesticides level of non-occupational exposure women and risk of breast cancer:a case-control study].

OBJECTIVE: To describe exposure level of organochlorines pesticides residues in non-occupational exposure population in China and testify the hypothesis that organochlorine pesticides exposure may be the risk factor to human breast cancer. METHODS: A case-control study based on community was designed. 90 new diagnostic breast cancer patients from the Second Hospital of Sichuan Province, and 136 health women from community, who settled down in the same district as case were enrolled. The risk factors of breast cancer were investigated by a questionnaire. GC-ECD was used to measure the serum level of Organochlorines pesticide residues. The adjusted odds rations (OR) of organochlorines pesticides residues to breast cancer were evaluated by logistic regression model. RESULTS: 8 organochlorines pesticide residues including p, p'-DDT, p, p'-DDE, o, p'-DDT, p, p'-DDD and alpha, beta, gamma, delta-HCHs (hexachlorocyclohexane) could be detected in serum of cases and controls. The detecting rates of beta-HCH, p, p'-DDE and p, p'-DDT respectively were 91.2%, 92.1% and 91.2%. There were no significant differences of serum level of organochlorines pesticides residues between cases and controls (P > 0.05). After adjusting confounding factors, serum p,p'-DDT, p,p'-DDD, and delta-HCH level were positively related to the risk of breast cancer (adjusted OR > 2, P < 0.05) . High serum p,p'-DDT,p,p'-DDD and beta-HCH level were positively correlated to premenopausal women (adjusted ORs respectively were 3.59, 5.70 and 3.06, P < 0.05). CONCLUSION: Organochlorines pesticides resides, including DDTs and HCHs, may increase women's risk of breast cancer, particularly in premenopausal women in China.

[Study on serum organochlorines pesticides (DDTs) level, CYP1A1 genetic polymorphism and risk of breast cancer: a case control study].

OBJECTIVE: To study the potential effect of gene-environment interaction between CYP1A1 and serum dichlorodiphenyldichloroethane (DDT) levels on the risk of breast cancer in women, in China. METHODS: A case-control study was conducted. From Dec. 2003 to Sep. 2004, 104 women with histologically confirmed breast cancers and 154 noncancerous controls from a community were enrolled in this study. Risk factors information of breast cancer was investigated by a questionnaire. Serum p, p'-dichlorodiphenyldichloroethane (p, p'-DDT) and 1, 1-dichloro-2, 2-bis (p-chlorophenyl) ethylene (p, p'-DDE) levels were tested by GC-ECD. CYP1A1 m2 gene type was tested by allele special-PCR method. RESULTS: Serum DDT levels of case and control were (36.90 +/- 79.41) ng/ml and (50.60 +/- 150.70) ng/ml respectively. Serum 1, 1-dichloro-2, 2-bis (p-chlorophenyl) ethylene (p, p'-DDE) levels of case and control were (7.43 +/- 11.10) ng/ml and (8.96 +/- 11.30) ng/ml respectively. No statistically significant differences were found between the two groups with geometric mean t-test (P > 0.05). Compared with women who had homozygous wild-type CYP1A1 m2 genotype, significantly increased risks of breast cancer were found for women with the CYP1A1 m2 homozygous variant genotype [odds ratio (OR) = 2.61, 95% confidence interval (CI): 1.00 - 6.80]. Among premenopausal women, compared with women with homozygous wild-type of CYP1A1 genotype (Ile/Ile) and low serum DDT level (DDT serum level < or = 42.93 ng/ml), women with at least one variant allele of CYP1A1 m2 genotype and high serum DDT level (DDT serum level > or = 42.93 ng/ml) had higher risk of breast cancer (OR = 4.35, 95% CI: 1.140 - 16.950). CONCLUSIONS: CYP1A1 m2 genetic polymorphism was associated with increased risk of female breast cancer while DDT exposure might have increased the risk of breast cancer among premenopausal women with CYP1A1 m2 variant genotype.