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Abstract: Objective: To investigate the clinical characteristics, diagnosis and surgical treatment of intravenous leiomyomatosis (IVL), and outline the differences between Chinese and overseas cases. Methods: Clinical data of two IVL cases, treated in our hospital, were analyzed retrospectively and the related literature was also reviewed. The data of preoperative diagnostic rate, surgical procedures, and postoperative recurrence between patients in China and other countries were compared. Results: The first stage operation was performed successfully in 2 patients. However, they refused subsequent therapies, including a second stage operation to excise the remnants of the tumor, uterus, bilateral oviducts and ovaries, and anti-estrogen therapy. Both suffered from IVL recurrence, one at 6-month and the other at 9-month, and died at 16-month and 12-month respectively after the first stage surgery. Worldwide reports of 110 IVL cases were reviewed, which included 28 cases in China and 82 cases in other countries. In the majority of the Chinese patients, tumors only extended into the right atrium rather than the right ventricle (RA 22 cases vs RV 4 cases). However, among the overseas patients, the rate of extension into the right atrium was similar to that of extension into the right ventricle (RA 41 cases vs RV 38 cases). The rate of hysterectomies was not significantly different between Chinese and overseas patients (67.86% vs 55.9%, P=0.278). The rate of correct preoperative diagnosis in the Chinese patients was significantly lower than that in the overseas patients (32.14% vs 80%, P=0.000002), as well as the rate of complete excision of the tumor (22.7% vs 75.5%, P=0.000001). The proportion of patients who undergoing a single-stage or a two-stage operation was similar in Chinese and overseas patients. The recurrence rate was significantly higher in the Chinese patients than in the overseas patients (36.8% vs 9.1%, P=0.0055), and the patients with tumor recurrence were partial tumor excision patients. Conclusion: The possibility of IVL should be considered if echocardiography in female patients demonstrates a tumor in the right heart and a mass in the inferior vena cava (IVC). Further imaging should be performed to confirm the diagnosis. The correct diagnosis and accurate preoperative delineation of tumor extension are essential for an optimal surgical outcome. The key point in IVL treatment is the complete excision of tumors (single-stage or two-stage surgical procedure). [Copyright &y& Elsevier]

p21(Cip1) and p27(Kip1) are cyclin-dependent kinase inhibitors, which can arrest cell proliferation and serve as tumor suppressors. Reduced protein expression of p21(Cip1) and p27(Kip1) was frequently observed in a subset of cancers, including breast cancer. In this study, we hypothesized that genetic variants in CDKN1A (encode for p21(Cip1)) and CDKN1B (encode for p27(Kip1)) may modulate the risk of breast cancer. To test this hypothesis, we evaluated the associations of the polymorphisms of Ser31Arg and C+20T in CDKN1A and C-79T and Gly109Val in CDKN1B, as well as their combinations, with breast cancer risk in a case-control study of 368 breast cancer cases and 467 cancer-free controls in a Chinese population. We found that a significantly increased risk of breast cancer was associated with the variant genotypes of CDKN1B C-79T [adjusted OR = 1.43 (95% CI = 1.03-1.98) for -79TC/TT], compared with the -79CC genotype, but no associations were observed for other variant genotypes. However, the combined variant genotypes of the 4 loci were associated with a significantly increased breast cancer risk (adjusted OR = 1.49, 95% CI = 1.11-2.01 among subjects carrying 3 or more variant alleles), especially among premenopausal women (adjusted OR= 2.30, 95% CI = 1.45-3.66). Furthermore, in premenopausal women, this significant association remained unchanged, after including other individual risk factors in the multivariate logistic regression model, suggesting an independent role of CDKN1A and CDKN1B variants in breast cancer risk. Although the exact biological mechanism remains to be explored, our findings suggest possible involvement of CDKN1A and CDKN1B variants in the etiology of breast cancer. Further large and functional studies are needed to confirm our findings.

MDM2 is a phosphoprotein that interacts with P53 and inhibits its activity. Recently, a T/G substitution (SNP309) in the promoter of MDM2 was identified and has been demonstrated to be associated with an increased MDM2 expression and a significantly earlier age of onset of several tumors, including breast cancer. To test the hypothesis that this functional variant in the MDM2 promoter is associated with risk of breast cancer, we conducted a molecular epidemiological study of 366 breast cancer cases (BC), 263 patients with benign breast diseases (BBD) and 605 cancer-free controls in China, in which we genotyped this T/G variant and another common insertion/deletion polymorphism (Del1518) in the MDM2 promoter and evaluated the associations between these two polymorphisms and breast cancer risk. We found that the variant allele frequencies of these two polymorphisms were not statistically different between the cases and controls (SNP309G: 0.500, 0.542, and 0.506 in BC, BBD, and controls, respectively, and Del1518-: 0.296, 0.308, and 0.297 in BC, BBD, and controls, respectively). Logistic regression analyses revealed that the variant genotypes of both MDM2 SNP309 and Del1518 polymorphisms were not significantly associated with risk of breast cancer (adjusted OR, 1.03; 95% CI, 0.74-1.42 for SNP309 TG and GG; and adjusted OR, 1.09; 95% CI, 0.83-1.43 for Del1518 +/- and -/-). These findings suggest that these two MDM2 promoter variants may not play a major role in the etiology of breast cancer.

Background: Accumulative evidence suggests that low folate intake is associated with increased risk of breast cancer. Polymorphisms in genes involved in folate metabolism may influence DNA methylation, nucleotide synthesis, and thus individual susceptibility to cancer. Thymidylate synthase (TYMS) is a key enzyme that participates in folate metabolism and catalyzes the conversion of dUMP to dTMP in the process of DNA synthesis. Two potentially functional polymorphisms [a 28-bp tandem repeat in the TYMS 5'-untranslated enhanced region (TSER) and a 6-bp deletion/insertion in the TYMS 3'-untranslated region (TS 3'-UTR)] were suggested to be correlated with alteration of thymidylate synthase expression and associated with cancer risk., Methods: To test the hypothesis that polymorphisms of the TYMS gene are associated with risk of breast cancer, we genotyped these two polymorphisms in a case-control study of 432 incident cases with invasive breast cancer and 473 cancer-free controls in a Chinese population., Results: We found that the distribution of TS3'-UTR (1494del6) genotype frequencies were significantly different between the cases and controls (P = 0.026). Compared with the TS3'-UTR del6/del6 wild-type genotype, a significantly reduced risk was associated with the ins6/ins6 homozygous variant genotype (adjusted OR = 0.58, 95% CI = 0.35-0.97) but not the del6/ins6 genotype (OR = 1.09, 95% CI = 0.82-1.46). Furthermore, breast cancer risks associated with the TS3'-UTR del6/del6 genotype were more evident in older women, postmenopausal subjects, individuals with a younger age at first-live birth and individuals with an older age at menarche. However, there was no evidence for an association between the TSER polymorphism and breast cancer risks., Conclusion: These findings suggest that the TS3'-UTR del6 polymorphism may play a role in the etiology of breast cancer. Further larger population-based studies as well as functional evaluation of the variants are warranted to confirm our findings.

Interleukin 1beta (IL-1beta) is a multifunctional cytokine that upregulates the inflammatory response, and participates in carcinogenesis, malignant transformation, tumor growth, invasion and metastasis. Two potentially functional polymorphisms (T-31C and C-511T) in the IL-1beta gene promoter were suggested to be correlated with alteration of IL-1beta expression and therefore may be associated with cancer risk. To test the hypothesis that these 2 polymorphisms are associated with risk of breast cancer, we performed a case-control study of 365 breast cancer cases, 270 patients with benign breast diseases (BBD) and 631 cancer-free controls in a Chinese population. Multivariate logistic regression analyses revealed that increased risk of breast cancer was associated with IL-1beta-31C variant genotypes [adjusted odds ratio (OR)=1.28 and 95% confidence interval (CI)=0.91-1.80 for -31CT and 1.72 (95% CI=1.16-2.54) for -31CC], compared with the -31TT genotype. Similarly, IL-1beta-511T variant genotypes were also associated with increased risk of breast cancer (adjusted OR=1.20, 95% CI=0.86-1.67 for -511CT and adjusted OR=1.74, 95% CI=1.18-2.56 for -511TT), compared with the -511CC genotype. Furthermore, cancer risks associated with IL-1betaT-31C variant genotypes were more evident in older women, postmenopausal women and individuals with a later menarche age. Interestingly, although we did not find significant associations of these 2 variants with cancer risk when compared with the BBD patients, a 1.27-fold (95% CI=1.01-1.60) increased risk was observed with the -31C-511T common haplotype. These findings indicate that these 2 IL-1beta promoter variants may contribute to risk of developing breast cancer in the Chinese population., (Copyright (c) 2005 Wiley-Liss, Inc.)