Effects of reproductive and demographic changes on breast cancer incidence in China: A modeling analysis

Background: Breast cancer incidence is currently low in China. However, the distribution of reproductive and lifestyle risk factors for breast cancer among Chinese women is changing rapidly. We quantified the expected effect of changes in breast cancer risk factors on future rates of breast cancer in China. Methods: We first validated and calibrated the Rosner-Colditz log-incidence breast cancer model in Chinese women who participated in the Shanghai Women's Health Study cohort (N = 74 942). We then applied the calibrated model to a representative sample of Chinese women who were aged 35-49 years in 2001 using data from the Chinese National Family Planning and Reproductive Health Survey (NFPRHS, N = 17 078) to predict the age-specific and cumulative breast cancer incidence among all Chinese women of this age group. We evaluated the relative impact of changes in modifiable risk factors, including alcohol intake, parity, postmenopausal hormone use, and adult weight gain, on cumulative incidence of breast cancer. Results: Breast cancer incidence in China is expected to increase substantially from current rates, estimated at 10-60 cases per 100 000 women, to more than 100 new cases per 100 000 women aged 55-69 years by 2021. We predicted 2.5 million cases of breast cancer by 2021 among Chinese women who were 35-49 years old in 2001. Modest reductions in hormone and alcohol use, and weight maintenance could prevent 270 000 of these cases. Conclusions: China is on the cusp of a breast cancer epidemic. Although some risk factors associated with economic development are largely unavoidable, the substantial predicted increase in new cases of breast cancer calls for urgent incorporation of this disease in future health care infrastructure planning

Dietary and Other Risk Factors in The Aetiology of Cholelithiasis: A Case Control Study

We studied the effect of dietary factors and a variety of other risk factors on the development of cholelithiasis through a case control study

Highlights from the 24th conference on retroviruses and opportunistic infections, 13-16 February 2017, Seattle, Washington, USA

From the 13th to 16th February 2017, researchers from around the world convened for the 24th annual Conference on Retroviruses and Opportunistic Infections (CROI) at the Washington State Convention Center in Seattle, Washington. The conference was organised by the International Antiviral Society-USA (IAS-USA) in partnership with the CROI Foundation. The conference included over 1000 oral and poster presentations of peer-reviewed original research as well as lectures and symposia featuring insights from leading basic, translational and clinical researchers. Highlighted here are key data presented at the conference

Indoor Tanning and Non-Melanoma Skin Cancer: Systematic Review and Meta-Analysis

Objective: To synthesise the literature on indoor tanning and non-melanoma skin cancer. Design: Systematic review and meta-analysis. Data sources: PubMed (1966 to present), Embase (1974 to present), and Web of Science (1898 to present). Study selection: All articles that reported an original effect statistic for indoor tanning and non-melanoma skin cancer were included. Articles that presented no data, such as review articles and editorials, were excluded, as were articles in languages other than English. Data extraction: Two investigators independently extracted data. Random effects meta-analysis was used to summarise the relative risk of ever use versus never use of indoor tanning. Dose-response effects and exposure to indoor tanning during early life were also examined. The population attributable risk fraction for the United States population was calculated. Results: 12 studies with 9328 cases of non-melanoma skin cancer were included. Among people who reported ever using indoor tanning compared with those who never used indoor tanning, the summary relative risk for squamous cell carcinoma was 1.67 (95% confidence interval 1.29 to 2.17) and that for basal cell carcinoma was 1.29 (1.08 to 1.53). No significant heterogeneity existed between studies. The population attributable risk fraction for the United States was estimated to be 8.2% for squamous cell carcinoma and 3.7% for basal cell carcinoma. This corresponds to more than 170 000 cases of non-melanoma skin cancer each year attributable to indoor tanning. On the basis of data from three studies, use of indoor tanning before age 25 was more strongly associated with both squamous cell carcinoma (relative risk 2.02, 0.70 to 5.86) and basal cell carcinoma (1.40, 1.29 to 1.52). Conclusions: Indoor tanning is associated with a significantly increased risk of both basal and squamous cell skin cancer. The risk is higher with use in early life (<25 years). This modifiable risk factor may account for hundreds of thousands of cases of non-melanoma skin cancer each year in the United States alone and many more worldwide. These findings contribute to the growing body of evidence on the harms of indoor tanning and support public health campaigns and regulation to reduce exposure to this carcinogen

Oral Ingestion of Hexavalent Chromium through Drinking Water and Cancer Mortality in an Industrial Area of Greece - An Ecological Study

Background: Hexavalent chromium is a known carcinogen when inhaled, but its carcinogenic potential when orally ingested remains controversial. Water contaminated with hexavalent chromium is a worldwide problem, making this a question of significant public health importance. Methods: We conducted an ecological mortality study within the Oinofita region of Greece, where water has been contaminated with hexavalent chromium. We calculated gender, age, and period standardized mortality ratios (SMRs) for all deaths, cancer deaths, and specific cancer types of Oinofita residents over an 11-year period (1999 - 2009), using the greater prefecture of Voiotia as the standard population. Results: A total of 474 deaths were observed. The SMR for all cause mortality was 98 (95% CI 89-107) and for all cancer mortality 114 (95% CI 94-136). The SMR for primary liver cancer was 1104 (95% CI 405-2403, p-value < 0.001). Furthermore, statistically significantly higher SMRs were identified for lung cancer (SMR = 145, 95% CI 100-203, p-value = 0.047) and cancer of the kidney and other genitourinary organs among women (SMR = 368, 95% CI 119-858, p-value = 0.025). Elevated SMRs for several other cancers were also noted (lip, oral cavity and pharynx 344, stomach 121, female breast 134, prostate 128, and leukaemias 168), but these did not reach statistical significance. Conclusions: Elevated cancer mortality in the Oinofita area of Greece supports the hypothesis of hexavalent chromium carcinogenicity via the oral ingestion pathway of exposure. Further studies are needed to determine whether this association is causal, and to establish preventive guidelines and public health recommendations

Long non-coding RNAs and latent HIV : a search for novel targets for latency reversal

The latent cellular reservoir of HIV is recognized as the major barrier to cure from HIV infection. Long non-coding RNAs (lncRNAs) are more tissue and cell type-specific than protein coding genes, and may represent targets of choice for HIV latency reversal. Using two in vitro primary T-cell models, we identified lncRNAs dysregulated in latency. PVT1 and RP11-347C18.3 were up-regulated in common between the two models, and RP11-539L10.2 was down-regulated. The major component of the latent HIV reservoir, memory CD4+ T-cells, had higher expression of these lncRNAs, compared to naive T-cells. Guilt-by-association analysis demonstrated that lncRNAs dysregulated in latency were associated with several cellular pathways implicated in HIV latency establishment and maintenance: proteasome, spliceosome, p53 signaling, and mammalian target of rapamycin (MTOR). PVT1, RP11-347C18.3, and RP11-539L10.2 were down-regulated by latency reversing agents, suberoylanilide hydroxamic acid and Romidepsin, suggesting that modulation of lncRNAs is a possible secondary mechanism of action of these compounds. These results will facilitate prioritization of lncRNAs for evaluation as targets for HIV latency reversal. Importantly, our study provides insights into regulatory function of lncRNA during latent HIV infection

CD32+CD4+memory T cells are enriched for total HIV-1 DNA in tissues from humanized mice

CD32 has raised conflicting results as a putative marker of the HIV-1 reservoir. We measured CD32 expression in tissues from viremic and virally suppressed humanized mice treated relatively early or late after HIV-1 infection with combined antiretroviral therapy. CD32 was expressed in a small fraction of the memory CD4(+) T-cell subsets from different tissues in viremic and aviremic mice, regardless of treatment initiation time. CD32(+) memory CD4(+) T cells were enriched in cell associated (CA) HIV-1 DNA but not in CA HIV-1 RNA as compared to the CD32(-) CD4(+) fraction. Using multidimensional reduction analysis, several memory CD4(+)CD32(+) T-cell clusters were identified expressing HLA-DR, TIGIT, or PD-1. Importantly, although tissue-resident CD32(+)CD4(+) memory cells were enriched with translation-competent reservoirs, most of it was detected in memory CD32-CD4(+) T cells. Our findings support that CD32 labels highly activated/exhausted memory CD4(+) T-cell subsets that contain only a small proportion of the translation-competent reservoir

Gut dysbiosis associates with cytokine production capacity in viral-suppressed people living with HIV

BACKGROUND: People living with human immunodeficiency virus (PLHIV) are exposed to chronic immune dysregulation, even when virus replication is suppressed by antiretroviral therapy (ART). Given the emerging role of the gut microbiome in immunity, we hypothesized that the gut microbiome may be related to the cytokine production capacity of PLHIV.METHODS: To test this hypothesis, we collected metagenomic data from 143 ART-treated PLHIV and assessed the ex vivo production capacity of eight different cytokines [interleukin-1β (IL-1β), IL-6, IL-1Ra, IL-10, IL-17, IL-22, tumor necrosis factor, and interferon-γ] in response to different stimuli. We also characterized CD4 + T-cell counts, HIV reservoir, and other clinical parameters. RESULTS: Compared with 190 age- and sex-matched controls and a second independent control cohort, PLHIV showed microbial dysbiosis that was correlated with viral reservoir levels (CD4 + T-cell-associated HIV-1 DNA), cytokine production capacity, and sexual behavior. Notably, we identified two genetically different P. copri strains that were enriched in either PLHIV or healthy controls. The control-related strain showed a stronger negative association with cytokine production capacity than the PLHIV-related strain, particularly for Pam3Cys-incuded IL-6 and IL-10 production. The control-related strain is also positively associated with CD4 + T-cell level. CONCLUSIONS: Our findings suggest that modulating the gut microbiome may be a strategy to modulate immune response in PLHIV.</p