Associations of polymorphisms in the genes of FGFR2, FGF1, and RBFOX2 with breast cancer risk by estrogen/progesterone receptor status.

Genetic polymorphisms of fibroblast growth factor receptor 2 (FGFR2) have been demonstrated to be associated with breast cancer risk, presumably through elevation of FGFR2 expression. Fibroblast growth factor 1 (FGF1) and RNA binding protein fox-1 homolog 2 (RBFOX2), which are functionally related to FGFR2, may also associate with breast cancer risk. We investigated the associations between breast cancer risk and the polymorphisms of FGFR2 rs2981582, FGF1 rs250108, and RBFOX2 rs2051579 among 839 incident breast cancer cases and 863 age-matched controls in the Guangzhou Breast Cancer Study. Stratified odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by estrogen receptor (ER)/progesterone receptor (PR) status using multivariate logistic regression. FGFR2 rs2981582 was confirmed to be significantly associated with the risk of ER-positive but not ER-negative breast cancer. In contrast, FGF1 rs250108 was significantly associated with the risk of ER-negative breast cancer (OR (95% CI) = 1.68 (1.20-2.35) for CT + TT vs. CC genotype) but not ER-positive breast cancer. CA + AA genotypes at RBFOX2 rs2051579 were associated with a reduced risk of ER-negative (0.71 (0.52-0.97)) but not ER-positive breast cancer compared to the CC genotype. Similar results were observed when differentiating breast cancer cases by PR status. Neither of the pairs between the three SNPs had a significant interaction on breast cancer risk. Our findings show a suggestively stronger association between FGFR2 rs2981582 and ER-positive breast cancer risk and suggest a greater association of FGF1 rs250108 and RBFOX2 rs2051579 with ER-negative compared to ER-positive breast cancer.

[Association between urinary cadmium and clinicopathological characteristics of breast cancer].

OBJECTIVE: The aim of this study was to investigate the association between urinary cadmium and clinicopathological characteristics of breast cancer. METHODS: The clinicopathological characteristics of 240 patients with breast cancer were obtained and urine specimens were collected from October 2009 to July 2010. The concentration of urinary cadmium was determined by inductively coupled plasma mass spectrometry (ICP-MS). χ(2) test and Wilcoxon rank sum test were used to analyze whether urinary cadmium is associated with clinicopathological characteristics of breast cancer. RESULTS: The median concentration of urine cadmium of 240 patients was 1.99 µg/g (25th percentile, 1.32 µg/g; 75th percentile, 2.88 µg/g). HER-2 positive rate, regional/distant metastasis rate, and advanced stage rate in patients with the highest tertile of cadmium concentration were significantly higher than those in the patients with second and lowest Cd tertiles (P = 0.042, P = 0.028 and P = 0.017, respectively), and 28.2% vs. 16.5% for HER-2 and 47.2% vs. 32.0% for regional/distant metastasis, respectively. There were still significant associations between urinary cadmium levels and these clinicopathological parameters after being adjusted in age by unconditional logistic regression model, respectively (P < 0.05). CONCLUSIONS: The results of this study suggest that urinary cadmium levels are associated with the HER-2 status, regional/distant metastasis status and stages of breast cancer, respectively. Cadmium may induce highly aggressive breast cancer in humans.

Joint effects of Epstein-Barr virus and polymorphisms in interleukin-10 and interferon-γ on breast cancer risk.

BACKGROUND: The relationship between Epstein-Barr virus (EBV) and breast cancer (BC) is controversial. Interleukin-10 (IL-10) and interferon-γ (IFN-γ) are believed to play a critical role in the host's responses to EBV infection, and their genetic variations may modify the association of EBV with BC risk. METHODS: We examined serum levels of EBV viral capsid antigen (VCA) immunoglobulin A (IgA) and nuclear antigen-1 (EBNA-1) IgA along with the polymorphisms of IL-10 rs1800871 and IFN-γ rs2069705 in 354 incident BC cases and 504 age-matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariate logistic regression. RESULTS: VCA IgA and EBNA-1 IgA levels were positively associated with BC risk. IL-10 rs1800871 (TC/CC) was associated with a reduced BC risk (OR, 0.74 [95% CI, 0.55-1.00]) but had no interaction with EBV infection on BC risk. IFN-γ rs2069705 was not directly associated with BC risk but interacted with EBNA-1 IgA on BC risk. Among women with the CC genotype, EBNA-1 IgA seropositivity significantly increased the risk of BC compared to EBNA-1 IgA seronegativity (OR, 5.14 [95% CI, 1.76-14.98]). CONCLUSIONS: These results suggest that EBV may contribute to the risk of BC and that this contribution may be modified by genetic variations in IFN-γ.

Urinary strontium and the risk of breast cancer: a case-control study in Guangzhou, China.

Strontium has been widely used in industries like electronic and pharmacy. It has a carcinogenic potential, however, and no study has been conducted to evaluate its effects on cancer risk. The aim of this study was to explore the possible association between strontium and breast cancer risk in a case-control study including 240 incident invasive breast cancer patients and 246 age-matched controls. We measured the urinary concentrations of strontium by inductively coupled plasma mass spectrometry, and conducted face-to-face interviews to obtain information on potential breast cancer risk factors. Multivariable analysis was used to estimate the association. Creatinine-adjusted levels [median (25th, 75th) µg/g] of strontium were 155.59 (99.05, 230.70) in the breast cancer patients and 119.62 (81.97, 163.76) in the controls. Women in the highest tertile of strontium showed 124% increased risk of breast cancer, when compared with those in the lowest tertile after adjustment for the potential risk factors [OR (95% CI): 2.24 (1.42-3.81)]. This association was particularly strong for HER2 positive breast cancer [OR (95% CI): 10.92 (3.53-33.77)], and only occurred among premenopausal women. These results suggest a potential role of strontium in the development of breast cancer and urge further studies on the environmental contamination and the physiological and pathological mechanisms of strontium.

Modified effect of urinary cadmium on breast cancer risk by selenium.

BACKGROUND: Previous experimental studies have shown an antagonistic interaction between cadmium and selenium. We explored the interaction between cadmium and selenium on human breast cancer risk. METHODS: A case-control study, enrolled 240 incident invasive breast cancer patients and 246 age-matched controls from 2 hospitals, was conducted in Guangzhou, China. Inductively coupled plasma mass spectrometry was used to examine urinary concentrations of cadmium and selenium. Association and interaction of the metal levels with breast cancer risk were tested using generalized additive and logistic regression models. RESULTS: As continuous variables, urinary cadmium [OR (95% CI): 1.16 (1.01-1.34)] but not selenium was significantly linearly associated with breast cancer risk. As tertiles, urinary cadmium did not significantly increase breast cancer risk; whereas women with the second tertile of selenium concentration had a significantly decreased risk of breast cancer as compared with those in the lowest tertile [OR (95% CI): 0.50 (0.30-0.81)]. Among the women with the lowest tertile of selenium, the highest tertile of cadmium significantly increased the risk of breast cancer [OR (95% CI): 2.83 (1.18-6.86)] compared to the lowest tertile of cadmium. A multiplicative interaction was found between tertiles of cadmium and selenium on breast cancer risk (P=0.018), particularly among postmenopausal women. CONCLUSIONS: These results suggested that the association of urinary cadmium with breast cancer risk was modified by urinary selenium.

Association of Epstein-Barr virus and passive smoking with the risk of breast cancer among Chinese women.

Reactivation of Epstein-Barr virus (EBV), as indexed by the higher immunoglobulin A (IgA) antibody titers, was reported to be associated with an increased risk of breast cancer. Passive smoking plays a role in host immune responses and may modify the association of EBV with breast cancer. We carried out a case-control study using data from 349 incident breast cancer cases and 500 age-matched controls in the Guangzhou Breast Cancer Study to investigate the interactions of EBV antibodies and passive smoking on breast cancer risk. A higher risk of breast cancer was observed in passive smokers who were seropositive for EBV viral capsid antigen IgA or nuclear antigen-1 IgA in serum compared with those with the seronegativity and no passive smoking [odds ratio 3.13 (95% confidence interval, 1.76-5.56)]. There was a significant linear trend for the risk of breast cancer from IgA seropositivity with passive smoking, only IgA seropositivity, only passive smoking, to seronegativity without passive smoking (P<0.001), but the interaction in either multiplicative or additive models was not significant. No significant association was found between passive smoking and EBV IgA seropositivity. The present study confirmed the associations of EBV IgA antibodies and passive smoking with the risk of breast cancer and suggested that there was no synergic action between passive smoking and EBV IgA seropositivity on the risk of breast cancer.

[Interaction of body mass index and a polymorphism in gene of catalytic subunit of glutamate-cysteine ligase on breast cancer risk among Chinese women].

OBJECTIVE: To investigate the interaction of body mass index(BMI)and a single nucleotide polymorphism (SNP, rs17883901) in catalytic subunit of glutamate-cysteine ligase (GCLC) on breast cancer risk. METHODS: A total of 839 women with incident breast cancer and 863 age-matched controls without cancer were recruited at the same period in three affiliated hospitals of Sun Yat-sen University in Guangzhou from October 2008 to June 2010. GCLC rs17883901 was genotyped by MALDI-TOF-MS. Binary unconditional logistic regression was applied to calculate odds ratios and 95% confidence intervals. RESULTS: The difference of present BMI and BMI at age 20 was not statistically significant between cases and controls, either as the genotypes of GCLC. No association was found between BMI at present and premenopausal or postmenopausal breast cancer risk. But we found that women who had a BMI at age 20 of 18.5 to 22.9 had a marginally decreased risk of premenopausal breast cancer [OR and 95%CI:0.69(0.48, 1.00)]. Among women with CT/TT genotypes, whose present BMI was greater than 25 had a increased risk [OR and 95%CI:1.91(1.09, 3.36)] of breast cancer and a decreased risk [OR and 95%CI:0.56 (0.31,0.99)] with a BMI at age 20 of 18.5 to 22.9. There was a interaction between GCLC gene(rs17883901)and BMI at present in breast cancer risk (P = 0.043), which was not found between rs17883901 and BMI at age 20. CONCLUSION: Our findings indicate BMI at age 20 may be a protective factor of premenopausal breast cancer, while no association appears between GCLC(rs17883901) and breast cancer. Obesity at present may significantly increase the risk of breast cancer among women with CT/TT genotypes of GCLC (rs17883901).

Urinary rubidium in breast cancers.

BACKGROUND: Rubidium is a putative anticancer agent, but no studies have been performed on the association of rubidium levels in biospecimen with breast cancer risk and the potential as a biomarker of the risk assessment. METHODS: Survey data and urine specimens were collected from 240 women with incident invasive breast cancer before their treatments and 246 age-matched female controls between October 2009 and July 2010. Urinary concentrations of rubidium were determined by inductively coupled plasma mass spectrometry. RESULTS: Creatinine-adjusted levels [median (25th, 75th) ug/g] of rubidium in cases [2253.01(1606.81, 3110.46)] were significantly lower than that in the controls [2921.85 (2367.94, 4142.04)]. After adjustment for potential risk factors of breast cancer, women in the second and highest tertile decreased risk of breast cancer in a dose-dependent manner as compared with those in the lowest tertile [ORs and 95% CIs were 0.45 (0.27-0.73) and 0.22 (0.13-0.38), respectively]. The area under the receive-operating-characteristic curve for urinary rubidium level was 0.697 (95% CI: 0.650-0.743). CONCLUSIONS: The urinary levels of rubidium were significantly and inversely associated with risk of breast cancer and had potential to be a biomarker for breast cancer risk assessment.