Healthy lifestyle and breast cancer risk: A case-control study in Morocco

BackgroundSome modifiable risk factors have been independently associated with breast cancer (BC) risk in Moroccan women, but no studies have investigated their joint association. This study aimed to investigate the association between a Healthy Lifestyle Index (HLI) score and BC risk among Moroccan women.MethodsIn this case–control study, 300 incident BC cases and 300 controls, matched by age and area of residence were recruited. Cases were women newly-diagnosed with histopathologically–confirmed BC at the University Hospital in Fez, Morocco. Controls were randomly selected healthy women recruited from 6 primary health centers in Fez. HLI scores developed within this study were assigned to participants based on 11 factors (red and processed meat, white meat, cream, cheese, fish, fruit and vegetables, physical activity, BMI, smoking, alcohol consumption, and breastfeeding), where 0 was given to unhealthy and 0.5 or 1 to healthy levels of each factor. Conditional and unconditional logistic regression models were used to assess the association between HLI scores and BC risk.ResultsMean of HLI scores were 8.1 (±1.1) and 9.0 (±0.9) in cases and controls, respectively, p < 0.01. After adjusting for potential confounders, one-point increment in the HLI score was associated with 56% (95% CI, CI: 39–68%), 49% (95% CI: 30–63%), and 59% (95% CI: 40–72%) lower risks of BC in all, premenopausal, and postmenopausal women, respectively.ConclusionHigh HLI scores were associated with decreased risk of BC in Moroccan women. These findings suggest that BC prevention policies should include strategies for engaging Moroccan women in healthy lifestyles.     

Polymorphisms in the promoter region of ESR2 gene and breast cancer susceptibility

Genetic variations like single nucleotide polymorphisms (SNPs) in genes involved in estrogen biosynthesis, metabolism and signal transduction have been suggested to affect breast cancer susceptibility. In this study we tested the hypothesis that polymorphisms in the promoter of ESR2 gene may be associated with increased risk for breast cancer. We analyzed three SNPs in the promoter region of human ESR2 gene by means of allele-specific tetra-primer PCR. A total of 318 sporadic breast cancer cases and 318 age-matched controls were included in the study. With regard to homozygous genotypes, women with sporadic breast cancer more frequently carried the CC genotype of ESR2 promoter SNP rs2987983 (OR 1.99, p = 0.005). Calculation of allele positivity demonstrated that presence of T allele of this SNP was more frequent in healthy women. Our data suggest that a SNP in the promoter region of ESR2 gene might be able to affect breast cancer risk. These results further support the emerging hypothesis that ERβ is an important factor in breast cancer development.     

No association between genetic variants in angiogenesis and inflammation pathway genes and breast cancer survival among Chinese women

Background: Angiogenesis and inflammation are implicated in breast cancer prognosis; however, the role of individual germline variation in related genes is unknown. Methods: A two-stage candidate pathway association study was conducted among 6983 Chinese women. Stage 1 included 2884 women followed for a median of 5.7 years; Stage 2 included 4099 women followed for a median of 4.0 years. Cox proportional hazards regression was used to estimate the effects of genetic variants on disease-free survival (DFS) and overall survival (OS). Results: Stage 1 included genotyping of 506 variants in 22 genes; analysis was conducted for 370 common variants. Nominally significant associations with DFS and/or OS were found for 20 loci in ten genes in Stage 1; variants in 19 loci were successfully genotyped and evaluated in Stage 2. In analyses of both study stages combined, nominally significant associations were found for nine variants in seven genes; none of these associations surpassed a significance threshold level corrected for the total number of variants evaluated in this study. Conclusions: No association with survival was found for 370 common variants in 22 angiogenesis and inflammation pathway genes among Chinese women with breast cancer. Impact: Our data do not support a large role for common genetic variation in 22 genes in breast cancer prognosis; research on angiogenesis and inflammation genes should focus on common variation in other genes, rare host variants, or tumor alterations.     

Dietary fibre intake associated with reduced risk of oesophageal cancer in Xinjiang,China

Objective: To ascertain the relationship between dietary fibre intake and risk of oesophageal cancer in remote northwest China, where the cancer incidence is known to be high. Methods: A case–control study was conducted during 2008–2009 in the Urumqi and Shihezi, Xinjiang Uyghur Autonomous Region of China. Participants were 359 incident oesophageal cancer patients and 380 hospital-based controls. Information on habitual foods consumption was obtained by face-to-face interview, from which dietary fibre intakes were estimated using the Chinese food composition tables. Results: The oesophageal cancer patients reported lower intake levels of total dietary fibre and fibre derived from vegetables and fruits than those of controls. Overall, regular intake of fibre was inversely associated with the oesophageal cancer risk, the adjusted odds ratio being 0.47 (95% confidence interval 0.32–0.69) for the highest (>27 g) versus the lowest (<16 g) tertile of daily intake, with a significant dose-response relationship (p = 0.004). Similar reductions in risk were also apparent for high intake levels of vegetable fibre and fruit fibre, but to a lesser extent for cereal fibre. Conclusion: Habitual intake of dietary fibre was associated with a reduced risk of oesophageal cancer for adults in northwest China.     

Asthma,allergy and the risk of prostate cancer: Results from the Montreal PROtEuS study

BackgroundThe few previous studies examining the association between asthma or allergy and prostate cancer (PCa) risk were inconclusive. This study aimed to evaluate these associations, and to explore in details the possible influence of current versus former allergic condition, age at onset, time since onset, and duration of each allergic condition.MethodsDetailed information on self-reported asthma and allergy was collected in the context of a large population-based case–control study conducted in Montreal, Canada. Study subjects included 1936 cases, diagnosed between 2005 and 2009, and 1995 population controls. Unconditional multivariate logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusting for age, ancestry and familial history of prostate cancer.ResultsThe ORs were 1.11 (95% CI: 0.89–1.40) and 0.98 (95% CI: 0.84–1.14) for ever reporting of asthma and allergy, respectively. These ORs did not substantially vary according to status (former or current), age at onset, time since onset, and duration of each allergic condition. PCa screening was not associated with allergic diseases reporting.ConclusionsOverall, our findings are in line with the absence of an association between a history of asthma or allergy, and PCa risk.     

The contribution of SIPA1 and RRP1B germline polymorphisms to breast cancer phenotype,lymph node status and survival in a group of Lithuanian young breast cancer patients

The germline polymorphisms in signal-inducing proliferation-associated protein 1 (SIPA1) and ribosomal RNR processing 1B (RRP1B) might be involved in breast cancer metastasis. The aim of this study was to analyze how SIPA1 and RRP1B polymorphisms contribute to breast cancer phenotype, lymph node status and survival. A group of 100 young, I–II stage breast cancer patients were analyzed for SIPA1 and RRP1B polymorphisms with PCR-RFLP assay. SIPA1 c.2760G?>?A, c.545C?>?T and RRP1B c.436T?>?C polymorphisms were associated with lymph node status, survival and tumor grade, respectively. Our results suggest that SIPA1 and RRP1B germline polymorphisms are important for breast cancer prognosis.     

Pregnancy, progesterone and progestins in relation to breast cancer risk

In the last two decades the prevailing opinion, supported by the “estrogen augmented by progesterone” hypothesis, has been that progesterone contributes to the development of breast cancer (BC). Support for this opinion was provided by the finding that some synthetic progestins, when added to estrogen in hormone replacement therapy (HRT) for menopausal complaints, increase the BC risk more than estrogen alone. However, recent findings suggest that both the production of progesterone during pregnancy and the progesterone endogenously produced or exogenously administered outside pregnancy, does not increase BC risk, and could even be protective. The increased BC risk found with the addition of synthetic progestins to estrogen in HRT seems in all likehood due to the fact that these progestins (medroxyprogesterone acetate and 19-nortestosterone-derivatives) are endowed with some non-progesterone-like effects which can potentiate the proliferative action of estrogens. The use of progestational agents in pregnancy, for example to prevent preterm birth, does not cause concern in relation to BC risk.     

Loss of circadian clock gene expression is associated with tumor progression in breast cancer

Several studies suggest a link between circadian rhythm disturbances and tumorigenesis. However, the association between circadian clock genes and prognosis in breast cancer has not been systematically studied. Therefore, we examined the expression of 17 clock components in tumors from 766 node-negative breast cancer patients that were untreated in both neoadjuvant and adjuvant settings. In addition, their association with metastasis-free survival (MFS) and correlation to clinicopathological parameters were investigated. Aiming to estimate functionality of the clockwork, we studied clock gene expression relationships by correlation analysis. Higher expression of several clock genes (e.g., CLOCK, PER1, PER2, PER3, CRY2, NPAS2 and RORC) was found to be associated with longer MFS in univariate Cox regression analyses (HR<1 and FDR-adjusted P < 0.05). Stratification according to molecular subtype revealed prognostic relevance for PER1, PER3, CRY2 and NFIL3 in the ER+/HER2- subgroup, CLOCK and NPAS2 in the ER-/HER2- subtype, and ARNTL2 in HER2+ breast cancer. In the multivariate Cox model, only PER3 (HR = 0.66; P = 0.016) and RORC (HR = 0.42; P = 0.003) were found to be associated with survival outcome independent of established clinicopathological parameters. Pairwise correlations between functionally-related clock genes (e.g., PER2-PER3 and CRY2-PER3) were stronger in ER+, HER2- and low-grade carcinomas; whereas, weaker correlation coefficients were observed in ER- and HER2+ tumors, high-grade tumors and tumors that progressed to metastatic disease. In conclusion, loss of clock genes is associated with worse prognosis in breast cancer. Coordinated co-expression of clock genes, indicative of a functional circadian clock, is maintained in ER+, HER2-, low grade and non-metastasizing tumors but is compromised in more aggressive carcinomas.     

Food consumption,meat cooking methods and diet diversity and the risk of bladder cancer

BackgroundSince food metabolites are eliminated by the urinary tract, several studies have investigated the association between diet and bladder cancer risk. Recently, the World Cancer Research Fund International/American Institute for Cancer Research (WCRF/AICR) suggested a potential beneficial effect of some foods (mainly vegetables, fruit, and milk) in the development of bladder cancer. We investigated the association between food groups and bladder cancer risk, seeking insights into food diversity as well as meat cooking methods.MethodsData were derived from an Italian multicentre case–control study, conducted between 2003 and 2014, including 690 bladder cancer cases and 665 frequency-matched controls. Odds ratios (ORs) and the corresponding 95% confidence intervals (95%CIs) for various dietary aspects were estimated by unconditional logistic regression models adjusted for energy intake and the major known risk factors for bladder cancer.ResultsComparing the highest versus the lowest quartiles, consumption of vegetables (OR = 0.62; 95%CI: 0.44-0.88) and milk/yogurt (OR = 0.62; 95%CI: 0.44–0.87) reduced the risk of bladder cancer. Conversely, consumption of meat increased bladder cancer risk with an OR of 1.57 (95%CI: 1.07–2.31), particularly when the meat was stewed (OR = 1.47; 95%CI: 1.03–2.09) or roasted (OR = 1.41; 95%CI: 1.00–1.99). There was a suggestion that a diversified diet reduced the risk of bladder cancer, but this was not significant.ConclusionsOur study consolidates the role of diet in bladder cancer aetiology, showing a reduced risk for vegetable and milk/yogurt consumption and an increased risk for meat consumption, especially when the meat is stewed or roasted.     

Shift work and inter-individual differences in sleep and sleepiness

Inter-individual differences in tolerance for shift work have been studied primarily in terms of external factors affecting alertness on the job or the ability to rest and sleep while at home. However, there is increasing evidence that neurobiological factors play a role as well, particularly the major processes involved in the regulation of sleep and wakefulness. These include a sleep homeostatic process seeking to balance wakefulness and sleep and a circadian process seeking to promote wakefulness during the day and sleep during the night. Shift work is associated with a temporal misalignment of these two endogenous processes. During nightwork, this misalignment makes it difficult to stay awake during the nightshift and sleep during the day. However, inter-individual variability in the processes involved in sleep/wake regulation is substantial. Recent studies have demonstrated the existence of inter-individual differences in vulnerability to cognitive deficits from sleep loss. Moreover, these inter-individual differences were shown to constitute a trait. Interestingly, self-evaluations of sleepiness did not correspond well with the trait inter-individual variability in objective levels of performance impairment during sleep deprivation. Perhaps because of this discrepancy, in operational settings, the inter-individual differences in vulnerability to sleep loss do not appear to be limited due to self-selection mechanisms. Indeed, even among a highly select group of active-duty jet fighter pilots flying a series of simulated night missions, systematic inter-individual differences in performance impairment from sleep loss were still observed. There are significant personal and economic consequences to human error and accidents caused by performance deficits due to sleep loss. It is important, therefore, to study the inter-individual differences in the regulation of sleep and wakefulness in the work environment so that cognitive impairment during shift work may be better anticipated and prevented.     

Impaired expression of the mPer2 circadian clock gene in the suprachiasmatic nuclei of aging mice

The expression of circadian clock genes was investigated in the suprachiasmatic nuclei (SCN) of young adult and old laboratory mice. Samples were taken at two time points, which corresponded to the expected maximum (circadian time 7 [CT7]) or minimum (CT21) of mPer mRNA expression. Whereas the young mice had a stable and well-synchronized circadian activity/rest cycle, the rhythms of old animals were less stable and were phase advanced. The expression of mPer1 mRNA and mPer2 mRNA was rhythmic in both groups, with peak values at CT7. The levels of mClock and mCry1 mRNA were not different depending on the time of day and did not vary with age. In contrast, an age-dependent difference was found in the case of mPer2 (but not mPer1) mRNA expression, with the maximum at CT7 significantly lower in old mice. The decreased expression of mPer2 may be relevant for the observed differences in the overt activity rhythm of aged mice. (Chronobiology International, 18(3), 559-565, 2001)     

乳腺癌基因芯片数据使用探讨

随着生命科学的迅猛发展,生物信息量的急剧增加,大量基因芯片的实验数据是公开发布在Internet网上的,尤其是学术机构在发表论文时所使用的实验数据都可以免费提供给研究人员下载使用。如何能有效地、正确地利用这些数据资源,特别是在利用数据验证算法、训练模型等问题的研究中,查询和使用基因芯片数据库网上资源便显得非常重要。对与乳腺癌基因芯片有关的数据库的数据查询及使用进行研究和探讨。     

Nightshift work,chronotype, and genome-wide DNA methylation in blood

Molecular mechanisms underlying the negative health effects of shift work are poorly understood, which remains a barrier to developing intervention strategies to protect the long-term health of shift workers. We evaluated genome-wide differences in DNA methylation (measured in blood) between 111 actively employed female nightshift and 86 actively employed female dayshift workers from the Seattle metropolitan area. We also explored the effect of chronotype (i.e., measure of preference for activity earlier or later in the day) on DNA methylation among 110 of the female nightshift workers and an additional group of 131 male nightshift workers. Methylation data were generated using the Illumina Infinium HumanMethylation450 BeadChip (450K) Array. After applying the latest methylation data processing methods, we compared methylation levels at 361,210 CpG loci between the groups using linear regression models adjusted for potential confounders and applied the false-discovery rate (FDR) ≤ 0.05 to account for multiple comparisons. No statistically significant associations at the genome-wide level were observed with shift work or chronotype, though based on raw P values and absolute effect sizes, there were suggestive associations in genes that have been previously linked with cancer (e.g., BACH2, JRK, RPS6KA2) and type-2 diabetes (e.g., KCNQ1). Given that our study was underpowered to detect moderate effects, examining these suggestive results in well-powered independent studies or in pooled data sets may improve our understanding of the pathways underlying the negative health effects of shift work and the influence of personal factors such as chronotype. Such an approach may help identify potential interventions that can be used to protect the long-term health of shift workers.     

Risk factors for breast cancer in the breast cancer risk model study of Guam and Saipan

BackgroundChamorro Pacific Islanders in the Mariana Islands have breast cancer incidence rates similar to, but mortality rates higher than, those of U.S. women. As breast cancer risk factors of women of the Mariana Islands may be unique because of ethnic and cultural differences, we studied established and suspected risk factors for breast cancer in this unstudied population.MethodsFrom 2010–2013, we conducted retrospective case-control study of female breast cancer (104 cases and 185 controls) among women in the Mariana Islands. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each of various lifestyle-related factors from logistic regression of breast cancer, in all women and in pre- and postmenopausal women separately. Tests for interaction of risk factors with ethnicity were based on the Wald statistics for cross-product terms.ResultsOf the medical and reproductive factors considered — age at menarche, breastfeeding, number of live births, age at first live birth, hormone use, and menopause — only age at first live birth was confirmed. Age at first live birth, among parous women, was higher among cases (mean 24.9 years) than controls (mean 23.2 years); with increased breast cancer risk (OR = 2.53; 95% CI, 1.04–6.19 for age ≥ 30y compared to <20y, P for trend = 0.01). Of the lifestyle factors —body mass index, waist circumference, physical activity, alcohol and betel-nut intake, and education — only waist circumference (OR = 1.65; 95% CI 0.87–3.14 for the highest tertile group compared to the lowest, P for trend = 0.04) was significantly associated with breast cancer risk and only in Filipino women. The association with many other established risk factors, such as BMI, hormone use and physical activity, were in the expected direction but were not significant. Associations for family history of breast cancer and alcohol intake were not evidentConclusionsThe results provide a basis for cancer prevention guidance for women in the Mariana Islands.     

Identification of genes modulated by interferon gamma in breast cancer cells

Interferon gamma (IFNγ) plays a context-dependent dual tumor-suppressor and pro-tumorigenic roles in cancer. IFNγ induces morphological changes in breast cancer (BC) cells with or without estrogen receptor alpha (ERα) expression. However, IFNγ-regulated genes in BC cells remain unexplored. Here, we performed a cDNA microarray analysis of MCF-7 (ERα+) and MDA-MB-231 (HER2-/PR-/ERα-) cells with and without IFNγ treatment. We identified specific IFNγ?modulated genes in each cell type, and a small group of genes regulated by IFNγ common in both cell types. IFNγ treatment for an extended time mainly repressed gene expression shared by both cell types. Nonetheless, some of these IFNγ-repressed genes were seemingly deregulated in human mammary tumor samples, along with decreased IFNGR1 (an IFNγ receptor) expression. Thus, IFNγ signaling-elicited anti-tumor activities may be mediated by the downregulation of main IFNγ target genes in BC; however, it may be deregulated by the tumor microenvironment in a tumor stage-dependent manner.