[Geneco]

Need some advice ish "fake" news or karma lai riao?

https://www.cureus.com/articles/196...dose-during-the-covid-19-pandemic-in-japan#!/

Miki Gibo • Seiji Kojima • Akinori Fujisawa • Takayuki Kikuchi • Masanori Fukushima

Published: April 08, 2024

DOI: 10.7759/cureus.57860

Peer-Reviewed

Conclusions
Statistically significant increases in age-adjusted mortality rates of all cancer and some specific types of cancer, namely, ovarian cancer, leukemia, prostate, lip/oral/pharyngeal, pancreatic, and breast cancers, were observed in 2022 after two-thirds of the Japanese population had received the third or later dose of SARS-CoV-2 mRNA-LNP vaccine. These particularly marked increases in mortality rates of these ERα-sensitive cancers may be attributable to several mechanisms of the mRNA-LNP vaccination rather than COVID-19 infection itself or reduced cancer care due to the lockdown. The significance of this possibility warrants further studies.

[Geneco]

Figure 1: Age-adjusted mortality rates (AMRs) over time and excess mortality in each month: all cancers.
(Left side) Observed age-adjusted mortality rates (AMRs) (per 100,000 population) are represented by a blue line with marks, the predicted trend by logistic regression analysis by a dashed line, and the 95% prediction intervals (PIs) by dotted lines. Markers are highlighted in yellow for years with figures exceeding 95% of the upper PI, and pink for years with figures exceeding 99% of the upper PI. The vertical line indicates the arrival of COVID-19 in Japan. There was a decreasing trend until 2020, but the decline stopped after 2021, with figures exceeding the 95% upper PI in 2021 and the 99% upper PI (the line was not shown) in 2022.

(Right side) The horizontal axis indicates each month during the pandemic in 2020, 2021, and 2022, while the vertical axis on the left side indicates the excess mortality (%), calculated as (observed AMR − predicted AMR in the corresponding month) / predicted AMR in the corresponding month*100. The predicted AMRs based on the 2010–2019 period preceding the COVID-19 pandemic were estimated by logistic regression analysis.

The ⁑ symbol signifies >99% upper PI, and † <95% lower PI. The vertical axis on the right side indicates the number of domestic vaccinations and deaths attributed to COVID-19.

Monthly excess mortalities exceeded the 99% upper PI for the first time in August 2021, coinciding with the peak of the first and second mass vaccinations, and once again exceeded the 99% upper PI for four months from May 2022, two months after the peak of the third mass vaccination.

[Geneco]

Cancer development by SARS-CoV-2 mRNA vaccine
In our study, the AMRs of ovarian cancer, leukemia, prostate, lip/oral/pharyngeal, pancreatic, and breast cancers increased significantly beyond the predicted rates, especially in 2022. All of these cancers are known as estrogen and estrogen receptor alpha (ERα)-sensitive cancers [78-83]. Recent research by Solis et al. on the binding ability of S-protein of SARS-CoV-2 against over 9,000 human proteins has shown that S-protein specifically binds to ERα and upregulates the transcriptional activity of ERα. The addition of estradiol (E2) to human breast cancer cells causes proliferation of the cancer cells, whereas the addition of raloxifene, a selective ERα modulator, inhibits proliferation. Breast cancer cells grow when S is added instead of E2, and the addition of raloxifene inhibits their growth. Solis et al. also mentioned that the finding of S-ERα cytosolic colocalization may lead to a potentiation of membrane-bound ERα signaling [84]. Membrane-bound ERα has been implicated in many pathways, including the activation of c-Myc, which promotes the cell cycle and impacts cancer development [85].

ERα-mediated transcription may induce endogenous DNA double-strand breaks (DSBs) in ER-sensitive cancers [86]. Studies have shown that transcriptionally activated ERα induces DSBs by topoisomerase II and the recently known R-loop/G-quadruplex structures formation, significantly increasing the need for BRCA1 for their repair in breast cancer cells [87-89]. One study showed nuclear translocation of mRNA and S protein with the nuclear localization signal [90], and an in silico bioinformatic analysis showed interactions between the S2 subunit of S-protein and BRCA1, BRCA2, and P53 [91], possibly resulting in their sequestration and dysfunction. The possible co-occurrence of high BRCA1 demand to repair DNA damage caused by activated transcription via ERα bound with S-protein along with dysfunction of BRCA1 sequestrated by S-protein raises concerns about increased cancer risk in ERα-sensitive cells in mRNA-LNP SARS-CoV-2 vaccine recipients.

As mentioned above, there is also great concern about the risk of dysfunction in the crucial cancer suppressor genes, brca2 and P53, as well as BRCA1, through mechanisms involving downregulation of IRF9 through interference by specific miRNA in exosomes [26] and the possible sequestration by the S2 subunit of S-protein in the vaccine [91]. Impaired BRCA1 activity is associated with higher risk of breast, uterine, and ovarian cancer in women and prostate cancer in men, as well as moderately higher risk of pancreatic cancer in both men and women [92]. BRCA2-associated cancers include breast and ovarian cancer in women, prostate and breast cancer in men, and acute myeloid leukemia in children [26]. These findings are highly consistent with our results.

Additional factors that may contribute to the development of cancer are being investigated. Since endogenous ROS causes oxidative DNA damage [93], excessive oxidative stress resulting from the downregulation of ACE2 by S-protein [57] may contribute to cancer development. One study showed that the downregulation of the Mas receptor promotes the metastasis of epithelial ovarian cancer [94]. ACE2 receptor, bound by S-protein after mRNA-LNP vaccination, may directly cause downregulation and subsequent dysfunction of the Mas receptor, possibly leading to an increased risk of metastasis in vaccinated women with ovarian cancer. The observation that injected LNPs accumulate particularly in the ovaries and bone marrow [38] could better explain our findings of excess mortalities from ovarian cancer and leukemia in 2022. According to an analysis of scientific literature about sex hormone receptors in head and neck squamous cell carcinoma (HNSCC), ERα plays various roles in the biopathology of HNSCC, particularly oropharyngeal cancer. These include promoting DNA hypermutation, facilitating HPV integration, and cooperating with epithelial growth factor receptor (EGFR) [82]. This may explain the increased mortality of lip/oral/pharyngeal cancer in our study.

A recent study showed that SARS-CoV-2 RNA could be reverse-transcribed to DNA and integrated into the human cell genome in vitro [95]. Another study reported that transfected mRNA in the human cells exposed to BNT162b2 leads to unsilencing of the endogenous retrotransposon long interspersed element-1 (LINE-1) and reverse transcription of vaccine mRNA sequences to DNA in the nucleus [96]. Accumulation of vaccine mRNA and reverse-transcribed DNA molecules in the cytoplasm could be expected to induce chronic autoinflammation, autoimmunity, DNA damage, and cancer risk in susceptible individuals [97].

The U.S. Food and Drug Administration (FDA) states in its guidance for the production of viral vaccines for infectious disease, "There are several potential mechanisms by which residual DNA could be oncogenic, including the integration and expression of encoded oncogenes or insertional mutagenesis following DNA integration" [98]. The FDA's guidelines are essential for Japan because Japan's special emergency use authorization depended on FDA approval during the COVID-19 pandemic [99]. Recently, some researchers have reported that several lots of Pfizer-BioNTech and Moderna vaccines contain a certain amount of double-stranded DNA fragments from residual plasmid vectors [100,101]. Some of them mentioned that the amount of residual DNA exceeds the regulatory limits for residual DNA set by the FDA. Given these reports and the FDA's regulatory statement, further investigation is required to determine whether the observed excess cancer deaths following mass vaccination were linked to reported residual DNA in the vaccine.

[Geneco]

Figure 2: Excess mortality during the pandemic in 2020, 2021, and 2022 (upper) and crude cancer deaths in 2022 (lower) in each age group.
Excess age-specific mortality = (observed ASMR − predicted ASMR) / predicted ASMR * 100 (%). Predicted ASMRs based on the 2010-2019 period preceding the COVID-19 pandemic were calculated using logistic regression. The ⁑ symbol signifies >99% upper PI, * >95% upper PI, and †<95% lower PI. 2020, deficit mortality was observed in most age groups except for the 75–79 age group. However, mortality increased gradually in 2021 and more remarkably in 2022 in almost all age groups except for the 65–69 and 85+ age groups. In the 75–79 age group, excess mortality was 3.9% (95%CI: 2.6, 5.3) in 2020, 7.9% (95%CI: 6.4, 9.5) in 2021, and 9.5% (95%CI: 7.8, 11.4) in 2022, exceeding the 99% upper PIs. In the 80–84 age group, excess mortality was 2.9% (1.4, 4.5) in 2022, exceeding the 95% upper PI. No statistical significance was detected in the younger age groups, which had few deaths. The chart below shows that the number of deaths from all cancers was highest in the 80–84 age group.

[Geneco]

https://www.youtube.com/watch?v=onww2X-ecfg

[Geneco]

Turbo cancer ah turbo cancer lolololol...

[Rainforest]

But back home still asking us to jab wor.... Hmmmm

[Geneco]

Moh still haven't pofma this peer review research yet lolololol...

[ODA TETSURO]

Meanwhile P&M developing medicines for cancers.

[watchfirst9]

Moh still haven't pofma this peer review research yet lolololol...

PPP should have put research reports instead some dr names profile. 

https://www.youtube.com/shorts/gAuI1wCqyus

[Geneco]

Ups for pofma...