The effect of cyclin D1 (CCND1) G870A-polymorphism on breast cancer risk is modified by oxidative stress among Chinese women in Singapore

Cyclin D1 (CCND1), an intracellular cell-cycle regulatory protein with checkpoint function, can promote cell proliferation or induce growth arrest and apoptosis depending on the cellular context. We hypothesized that the direction of the association between the (CCND1) G870A-polymorphism and breast cancer risk may be modified by dietary and genetic factors influencing the oxidant-antioxidant balance, such as a dietary pattern with a high intake of n-6 fatty acids and a low intake of n-3 fatty acids, or a genetic profile that is deficient in glutathione S-transferases. We tested our hypothesis in a case-control study nested into the Singapore Chinese Health Study, a prospective investigation of diet and cancer in 63 000 Chinese men and women. Genomic DNA collected from 258 incident cases of breast cancer and 670 female cohort controls was examined for CCND1, GSTM1, GSTT1 and GSTP1 genes using fluorogenic 5′-nuclease assay. Unconditional logistic regression models were used to assess the effects with adjustment for potential confounders. All statistical tests were two-sided. The heterozygous CCND1 GA genotype significantly reduced the breast cancer risk in all subjects (OR = 0.67, 95% CI 0.45-0.99) when compared with the GG genotype. The association was restricted to women with a high (above median value) intake level of n-6 fatty acids (OR = 0.51, 95% CI 0.30-0.87), a low (below median value) intake level of the antagonistic marine n-3 fatty acids (OR = 0.54, 95% CI 0.32-0.93) or a total lack of the antioxidative GSTM1 (OR = 0.44, 95% CI 0.25-0.80) or GSTT1 genes (OR = 0.46, 95% CI 0.24-0.87). The effects were consistently stronger in cases with advanced disease. The AA genotype did not affect breast cancer risk. The results of this study are compatible with the hypothesis that the oxidant-antioxidant balance in cells is an important determinant of the direction of the cyclin D1 effect, leading either to cell proliferation or cell deat

The effect of the cyclin D1 (CCND1) A870G polymorphism on colorectal cancer risk is modified by glutathione-S-transferase polymorphisms and isothiocyanate intake in the Singapore Chinese Health Study

Cyclin D1 (CCND1) regulates cellular decision between proliferation and growth arrest. Despite the functional relevance of the CCND1 A870G single nucleotide polymorphism (SNP) published results on its association with colorectal cancer (CRC) were inconsistent. We examined the association between this CCND1 genotype and CRC in the Singapore Chinese Health Study, a prospective investigation of diet and cancer in 63 000 Chinese men and women. We explored the hypothesis that inconsistency regarding the CCND1/CRC association may be attributable to the modifying effect of additional CRC risk factors. Since GSTM1/GSTT1 genotype and dietary isothiocyanate (ITC) intake had previously been identified as CRC risk factors in this cohort, we now explored if they influenced the CCND1/CRC association. In a nested case-control study within the Singapore Cohort, genomic DNA collected from 300 incident CRC cases and 1169 controls was examined for CCND1, GSTM1, GSTT1 and GSTP1 polymorphisms. Unconditional logistic regression was used to assess genotype effects on cancer risk. No main effect of CCND1 was observed, yet the CCND1 effect was influenced by ITC intake and GST genotypes. The presence of at least one CCND1 A-allele was associated with increased risk among low dietary ITC consumers (intake below median value for the cohort) with a high-activity GST profile (≥2 of the 3 GST genotypes classified non-null or high-activity) [odds ratio (OR) = 2.05; 95% confidence interval (CI), 1.10-3.82]. In contrast, the presence of at least one A-allele was associated with a decreased risk among all remaining subjects (OR = 0.56; 0.36-0.86) (P for interaction = 0.01). Recent studies indicate that ITCs inhibit cell proliferation and cause apoptosis through pro-oxidant properties. The results of our current study on CRC and those of our previous breast cancer study are compatible with the notion of oxidative stress in target cells as important determinant of direction and magnitude of the CCND1 effec

Impact of obesity on diagnosis and treatment of breast cancer

In this population-based study, we evaluated the impact of obesity on presentation, diagnosis and treatment of breast cancer. Among all women diagnosed with invasive breast cancer in the canton Geneva (Switzerland) between 2003 and 2005, we identified those with information on body mass index (BMI) and categorized them into normal/underweight (BMI <25kg/m2), overweight (BMI ≥-<30kg/m2) and obese (BMI ≥30kg/m2) women. Using multivariate logistic regression, we compared tumour, diagnosis and treatment characteristics between groups. Obese women presented significantly more often with stage III-IV disease (adjusted odds ratio [ORadj]: 1.8, 95% CI: 1.0-3.3). Tumours ≥1cm and pN2-N3 lymph nodes were significantly more often impalpable in obese than in normal/underweight patients (ORadj 2.4, [1.1-5.3] and ORadj 5.1, [1.0-25.4], respectively). Obese women were less likely to have undergone ultrasound (ORadj 0.5, [0.3-0.9]) and MRI (ORadj 0.3, [0.1-0.6]) and were at increased risk of prolonged hospital stay (ORadj 4.7, [2.0-10.9]). This study finds important diagnostic and therapeutic differences between obese and lean women, which may impair survival of obese women with breast cancer. Specific strategies are needed to optimize the care of obese women with or at risk of breast cance

Diversity management in the context of remote-working management: a longitudinal study

Purpose: The aim of the present study is twofold; firstly, it intends to investigate the level of perceived discrimination among employees in the context of remote working. Secondly, the paper draws on the results to propose initial insights on the role of the diversity management in the context of remote working. Theoretical background: The Sars-CoV-2 pandemic caused a shift in working methods and processes leading organisations to apply and maintain agile working procedures, namely, remote working. In this context, organisational processes towards remote working practices have been facilitated by the presence of management sensitive to work-life balance dimensions while respecting the socio-demographic characteristics of employees. However, questions on how and to what extent equality and diversity management, and in general to diversity climate, are still open. That is, the presence of a scarce Management of Diversities and an already ineffective Climate of Diversity could influence counterproductive effects in the remote working conduction. With a lack of inclusive practices, remote working may be related to higher levels of inequity as it is easier to exert new forms of discrimination such as cyberbullying and digital micro-aggressions. Design/Methodology/Approach/Intervention: Given this consideragtions, the study aims at explore the level of perceived discrimination in the context of remote working via a longitudinal survey. An online questionnaire has been submitted 240 SMEs employees in three different time sessions, one month apart. It was submitted between February and May 2020 and was adapted to investigate any change during the lockdown period. The constructs concerning the climate of diversity (Subtle and Overt Discrimination, Diversity Climate, Diversity and Equality Management) were investigated in association with different types of discrimination (e.g., gender, age, ethnicity, culture, religion, sexual orientation, physical appearance, and body art). Results obtained or expected: The literature shows how an effective equality and diversity management and a positive diversity climate bring a substantial benefit to the employees’ quality of life. Among the results, the outmost evidence concerns the role of diversity management on the diversity climate and subtle discrimination have been found. When lower levels of diversity management are present, the diversity climate decreases while the level of perceived discrimination increases. Limitations: Part of the sample gradually left the longitudinal survey at different stages. Research/Practical Implications: The results of the present study are relevant both for directing further studies on the topic of remote working and for organisations wishing to implement remote working effectively. Additionally, such results could increase the awareness about the management of discrimination-oriented behaviour. Intended audience: Both academic, and Practitioner

The effect of cyclin D1 (CCND1) G870A-polymorphism on breast cancer risk is modified by oxidative stress among Chinese women in Singapore

Cyclin D1 (CCND1), an intracellular cell-cycle regulatory protein with checkpoint function, can promote cell proliferation or induce growth arrest and apoptosis depending on the cellular context. We hypothesized that the direction of the association between the (CCND1) G870A-polymorphism and breast cancer risk may be modified by dietary and genetic factors influencing the oxidant-antioxidant balance, such as a dietary pattern with a high intake of n-6 fatty acids and a low intake of n-3 fatty acids, or a genetic profile that is deficient in glutathione S-transferases. We tested our hypothesis in a case-control study nested into the Singapore Chinese Health Study, a prospective investigation of diet and cancer in 63,000 Chinese men and women. Genomic DNA collected from 258 incident cases of breast cancer and 670 female cohort controls was examined for CCND1, GSTM1, GSTT1 and GSTP1 genes using fluorogenic 5'-nuclease assay. Unconditional logistic regression models were used to assess the effects with adjustment for potential confounders. All statistical tests were two-sided. The heterozygous CCND1 GA genotype significantly reduced the breast cancer risk in all subjects (OR=0.67, 95% CI 0.45-0.99) when compared with the GG genotype. The association was restricted to women with a high (above median value) intake level of n-6 fatty acids (OR=0.51, 95% CI 0.30-0.87), a low (below median value) intake level of the antagonistic marine n-3 fatty acids (OR=0.54, 95% CI 0.32-0.93) or a total lack of the antioxidative GSTM1 (OR=0.44, 95% CI 0.25-0.80) or GSTT1 genes (OR=0.46, 95% CI 0.24-0.87). The effects were consistently stronger in cases with advanced disease. The AA genotype did not affect breast cancer risk. The results of this study are compatible with the hypothesis that the oxidant-antioxidant balance in cells is an important determinant of the direction of the cyclin D1 effect, leading either to cell proliferation or cell death

Impact of obesity on diagnosis and treatment of breast cancer

10.1007/s10549-009-0459-1Breast Cancer Research and Treatment1201185-19