| Objective:To understand distribution of the quinone oxidoreductase 1(quinone oxido-reductase 1, NQO1) gene C609 Tpolymorphism surrounding Guilin area, to explore the relationship between NQO1 C609 T polymorphism,environmental factors and genetic susceptibility to breast cancer, combined with the clinical and pathological features of breast cancer patients( eg: ER, PR, HER-2, Ki-67) for the patient group for molecular typing, to analysize the relationship between NQO1 C609 T polymorphism and molecular typing of breast cancer. Method:we collected demographic and environmental exposure information, etc about 248 cases of female breast cancer patient in affiliated Hospital of Guilin Medical College from Oct. 15 th. 2012 to Feb. 15 th. 2014 and 284 healthy female from Mar. 1st. 2013 to Dec. 30 th. 2013 in the same hospital, using case-control study of hospital-based collection. By referring to outpatient and inpatient medical records, we perfected blood biochemical parameters of patients group and imaging diagnosis and so on, using Taq Man MGB fluorescence quantitative polymerase chain reaction in peripheral blood of both groups surveyed NQO1 gene C609 T polymorphism was typed, while detecting gene expression of ER,PR, HER-2 and Ki-67 in 248 cases of female breast cancer patients group using the mothod of immunohistochemical staining and FISH gene amplification. And apply SPSS 19.0 statistical software and multivariate unconditional Logistic regression to analysis relationship of NQO1 C609 T gene interactions and environmental factors and breast cancer molecular subtype. Result:1.The group surveyed a total of 532 cases( the patient group has 248 cases, the control group, 284 cases), the groups were age, ethnic balance comparable, after balancing test and comparison of risk factors showed that the age of first birth, breast-feeding time, who take birth control pills, passive smoking, drinking, staying up late, trauma, sleep at night wearing a bra, personality, physical activity and other factors distributed in the two groups was statistically significant difference(P<0.05), the two groups in education, menopause factor differences, eating regular or not was non- statistically significant(P>0.05). 2.Passive smoking, staying up late, trauma, sleep at night wearing a bra as the four factors risk of breast cancer risk factors, and gentle, regular physical exercise and other two factors protective factors, did not find the association primiparous aged>28 years old, had been taking birth control pills, breast-feeding period, alcohol consumption with the incidence of breast cancer. 3.Case and control groups were Hardy-Weinberg test results showed NQO1 gene C609 T genotype frequencies expected actual frequency difference was not statistically significant(χ2=0.009, P=0.923; χ2=0.608, P=0.435). 4.NQO1 locus CC, CT and TT genotype frequencies in case group were 27.42%, 49.60% and 22.98%, they were 34.51%, 50.35% and 15.14% respectively in the control group, the difference was statistically significant(P=0.039); Logistic regression analysis showed that, compared with the CC genotype, CT or TT genotype the risk of breast cancer OR values were 1.325 and 2.918, T allele frequency in case group(47.78%) than the control group(40.32%) increased(χ2=5.995, P=0.014), risk of breast cancer of carrying the T allele is 1.355 times than the C allele. Interaction analysis showed thatthere was interaction effect(P<0.05) between NQO1 C609 T gene polymorphism and often stays up late, passive smoking, trauma, sleep wear the bra, character and physical exercise, the OR values were 2.448, 3.960, 2.399, 1.981, 0.326 and 0.516. 5.There are 25 cases HER-2(++) in case group, excluding five cases of HER-2(++) who did not receive FISH testing, all the rest take FISH testing, eight cases were positive for gene amplification, 12 cases negative. Luminal A type accounted for 15.2%(37/243), Luminal B type accounted for 51.4%(125/243), HER-2 overexpression 19.8%(48/243), basal cell type 13.6%(33/243). 6. Patients carrying CT and TT genotypes whose ER, PR positive rate in patients with breast cancer was significantly higher(P<0.05) than carrying the CC genotype; However, HER-2 and Ki-67 protein expression was no difference between the two groups statistically significant(P>0.05); NQO1 gene C609 T polymorphism of the differences in different molecular typing of breast cancer cases was not statistically significant(P>0.05). Conclusions:1.Each genotype of NQO1 gene C609 T polymorphism accords Hardy-Weinberg genetic equilibrium law(P>0.05), the survey in this study can be considered to have the group representation. 2.Passive smoking, staying up late, trauma, sleep at night wearing a bra are risk factors to breast cancer, while gentle, regular physical exercise can reduce the risk of breast cancer. 3.There are three genotypes in NQO1 gene C609 T, which have significant differences in the frequency distribution between case group and control group,and there are significant differences of C, T allele frequency distributions in the two groups, which reveals that NQO1 gene C609 T polymorphism may have significance in the occurrence of breast cancer. 4.There is interaction among NQO1 gene C609 T polymorphism and often stays up late, passive smoking, trauma, sleep wearing bras,character and physical exercise, which indicates that the gene NQO1 C609 T polymorphism may be a genetic susceptibility factor for breast cancer, and can lead to cancer accord with environmental factors. 5.Compared with wild homozygouspatients, ER, PR positive rate of breast cancer in patients carried the mutant T allele was significantly higher while HER-2 expression and Ki-67 protein was no significant difference in the two groups, may be due to flavin protease activity of breast tissue in patients carried mutated gene decreased or disappeared, which inhibits the toxic effects of estrogen and its metabolites on human cells,and elevates levels of estrogen in tissue, the number of receptors increase, but the exact mechanism is unclear, which needs further experiments to verify. 6.This study has not found that C609 T polymorphism and NQO1 gene is related to molecular typing of breast cancer, may be relevant to few sample size, but NQO1(CT + TT) basal cell carcinoma of the breast in a lower miss rate, which provides reasonable explanation to breast cancer heterogeneity under molecular typing. |
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