Transgenerational effects of chemotherapy

Both male and female children born to women exposed to chemotherapy have fewer children

2018 Study Highlights

  • Cancer survival rates have been improving.
  • Little is known about the generational effects of chemotherapy-exposure.
  • The children of chemotherapy-exposed women have fewer live births compared to matched controls.
  • Further research needs to validate these findings.

Abstract

Background
There is little known about the transgenerational effect of chemotherapy. For example, chemotherapy is known to decrease fecundity in women. But if women are able to have offspring after chemotherapy exposure, do these children also have decreased fecundity?

Methods
This study is a retrospective cohort study utilizing the Utah Population Database (UPDB), a comprehensive resource that links birth, medical, death and cancer records for individuals in the state of Utah. The male and female children (F1 generation) of chemotherapy-exposed women (F0 generation) were identified. The number of live births (F2 generation) to this F1 generation was compared to two sets of chemotherapy-unexposed, matched controls using conditional Poisson regression models (regression coefficient, 95% confidence interval, P-value). The first unexposed was established using the general population and the second unexposed was established using first cousins to the F1 generation.

Results
The exposed F1 individuals had 77.2% fewer children (−1.48; −2.51 to −0.70; p = 0.001) relative to the unexposed general population. F1 males had 86.9% fewer children (−2.03; −4.91 to −0.51; p = 0.005) and F1 females had 70.5% fewer children (−1.22; −2.40 to −0.36; p = 0.016). When comparing to their unexposed cousins, the F1 generation (both sexes combined) had 74.3% (−1.36; −2.82 to −0.29; p = 0.029) fewer children.

Conclusion
The sons and daughters (F1 generation) of chemotherapy-exposed women have fewer live births when compared to both matched, unexposed general population and cousin controls. Chemotherapy may have a transgenerational effect in exposed women which needs further investigation.

Produits chimiques et cheveux

Etes-vous pollué(e) de perturbateurs endocriniens?

La gestion des perturbateurs endocriniens, vu par Gros.

Diethylstilbestrol Exposure and Leukemia, Brain Tumors, Wilms’ tumor

Childhood cancer: overview of incidence trends and environmental carcinogens

Abstract

An estimated 8000 children 0 to 14 years of age are diagnosed annually with cancer in the United States. Leukemia and brain tumors are the most common childhood malignancies, accounting for 30 and 20% of newly diagnosed cases, respectively.

From 1975 to 1978 to 1987 to 1990, cancer among white children increased slightly from 12.8 to 14.1/100,000. Increases are suggested for leukemia, gliomas, and, to a much lesser extent, Wilms’ tumor.

There are a few well-established environmental causes of childhood cancer such as radiation, chemotherapeutic agents, and diethylstilbestrol.

Childhood cancer: overview of incidence trends and environmental carcinogens, Environ Health Perspectives, NCBI PubMed PMID: 8549470, 1995 Sep.

Image of Sam via MLlive.

Many other agents such as electromagnetic fields, pesticides, and some parental occupational exposures are suspected of playing roles, but the evidence is not conclusive at this time.

Some childhood exposures such as secondhand cigarette smoke may contribute to cancers that develop many years after childhood.

For some exposures such as radiation and pesticides data suggest that children may be more susceptible to the carcinogenic effects than similarly exposed adults.

Diethylstilbestrol exposure and Medications

Transplacental carcinogenesis was established by the discovery in 1971 of vaginal adenocarcinoma in the daughters of women who took the hormone diethylstilbestrol (DES) during pregnancy to avoid miscarriages. This very rare cancer has been detected in girls as young as 7 years old, with most affected between 15 and 22 years of age. There are concerns that at older ages the exposed daughters may also have increased risk of squamous carcinomas of the vagina and cervix and cancers of the breast and that exposed sons may have excess testicular and prostate cancer . Continued followup of the DES-exposed daughters and sons is ongoing at the National Cancer Institute and may provide further information on the late effects of DES and on transplacental carcinogenesis in general.

Suspected, but less well-established, of being a transplacental carcinogen is phenytoin, an antiepileptic drug. There are reports of neuroblastoma and soft tissue sarcoma in children exposed in utero to phenytoin.

There have also been reports of excess brain tumors, neuroblastomas, leukemia, and retinoblastomas in children of women who used antinausea medications (e.g., Bendectin) during pregnancy. This issue had received considerable publicity, however, which may have affected recall of use by study subjects. One study used medical records, not subject recall, to assess exposure and did not show any associations.

There is one report of excess Wilms’ tumor among Swedish children whose mothers were exposed to penthrane (methoxyflurane) anesthesia during delivery. The excess risk was higher in females and increased with age at diagnosis.

Some medical treatments received during childhood also play a role in the development of childhood cancer. Chemotherapy and radiation therapy received for an initial childhood cancer can dramatically increase the risk for second cancers. For example, in one study children treated with alkylating agents for cancer have a 5-fold risk of subsequently developing leukemia. At high doses, the risk was increased as much as 25 times the expected rate of leukemia. Bone sarcomas were also elevated in children treated with radiation and chemotherapy.

The potent antibiotic chloramphenicol, given to treat life-threatening infectious conditions, has been linked to excess acute lymphocytic leukemia and acute nonlymphocytic leukemia in children in Shanghai. This association with leukemia is consistent with a report of bone marrow depression following use of chloramphenicol.

Parental use of illegal drugs has been linked to childhood cancer in a few reports. Marijuana use was associated with rhabdomyosarcoma, leukemia, and brain tumors. Cocaine use was also associated with rhabdomyosarcoma.

These exposures are difficult to study accurately and need further research, but prevention efforts clearly must continue for noncancer-related reasons even in the absence of convincing data on childhood cancer.

Click to dowload the complete article.

More DES DiEthylStilbestrol Resources

High dose of vitamin C kills cancer cells in mice

Human trials unlikely because drug companies cannot patent vitamins

image of oranges
High-dose vitamin C can boost the cancer-killing effect of chemotherapy in the lab and mice. Orange.

Getting all stressed out by vitamin C

Few experimental cancer therapies have incited as much debate as vitamin C. Yet the mechanistic effect of vitamin C on cancer cells is still poorly understood. Yun et al. studied human colorectal cancer cells with KRAS or BRAF mutations and found that they “handle” vitamin C in a different way than other cells, ultimately to their detriment (see the Perspective by Reczek and Chandel). Because a certain receptor is up-regulated in the mutant cells, they take up the oxidized form of vitamin C (dehydroascorbate). This leads to oxidative stress, inactivation of a glycolytic enzyme required by the mutant cells for growth, and finally cell death. Whether the selective toxicity of vitamin C to these mutant cells can be exploited therapeutically remains unclear.

Abstract

More than half of human colorectal cancers (CRCs) carry either KRAS or BRAF mutations and are often refractory to approved targeted therapies. We found that cultured human CRC cells harboring KRAS or BRAF mutations are selectively killed when exposed to high levels of vitamin C. This effect is due to increased uptake of the oxidized form of vitamin C, dehydroascorbate (DHA), via the GLUT1 glucose transporter. Increased DHA uptake causes oxidative stress as intracellular DHA is reduced to vitamin C, depleting glutathione. Thus, reactive oxygen species accumulate and inactivate glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Inhibition of GAPDH in highly glycolytic KRAS or BRAF mutant cells leads to an energetic crisis and cell death not seen in KRAS and BRAF wild-type cells. High-dose vitamin C impairs tumor growth in Apc/KrasG12D mutant mice. These results provide a mechanistic rationale for exploring the therapeutic use of vitamin C for CRCs with KRAS or BRAF mutations.

Study and Press Releases
  • Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH, science, 11 Dec 2015.
  • High dose of vitamin C kills cancer cells in mice, arstechnica, Nov 18, 2015.
  • Vitamin C ‘gives chemotherapy a boost’, BBC News, 9 February 2014.
  • Research continues to confirm that high doses of vitamin C injections destroy cancer, but don’t expect to hear that from Big Pharma, newstarget.

The Side Effects of Chemotherapy on the Body

Chemotherapy infographic, Healthline Editorial Team, 2014

chemotherapy-infographic
Visit Healthline to see the detailed effects of chemotherapy in an interactive format.

Chemotherapy drugs are powerful enough to kill rapidly growing cancer cells, but they also can harm perfectly healthy cells, causing side effects throughout the body.

More information

Alopecia cancer treatment side effect: from uncomfortable to life-changing

I survived cancer – but drugs left me with permanent alopecia

Shirley Ledlie was left with persistent significant Alopecia following breast cancer treatment with Taxotere drug. Image credit The Telegraph.

Studies show that long term hair loss, which can be caused by a cocktail of certain cancer drugs, has significant impact of quality of survival. Why isn’t more known about it?

Shirley Ledlie long-term Alopecia’s cause – significant and permanent hair loss – was a drug called Taxotere (Docetaxel), which, when combined into a “cocktail” with other chemotherapy drugs, causes “male pattern baldness“…

Read I survived cancer – but drugs left me with permanent alopecia,
The Telegraph, 03 Sep 2015.

Chemotherapy for near-death cancer patients does not improve “quality of life”

Chemotherapy Use, Performance Status, and Quality of Life at the End of Life

chemotherapy-drug image
Many patients with terminal cancer are offered chemotherapy in order to improve their quality of life. But according to a new study, the treatment does not improve quality of life for cancer patients who are near death – and may even worsen it for those who have good performance status. Chemotherapy drug by Nicki Dugan Pogue.

2015 Study Abstract

Importance
Although many patients with end-stage cancer are offered chemotherapy to improve quality of life (QOL), the association between chemotherapy and QOL amid progressive metastatic disease has not been well-studied. American Society for Clinical Oncology guidelines recommend palliative chemotherapy only for solid tumor patients with good performance status.

Objective
To evaluate the association between chemotherapy use and QOL near death (QOD) as a function of patients’ performance status.

Design, Setting, and Participants
A multi-institutional, longitudinal cohort study of patients with end-stage cancer recruited between September 2002 and February 2008. Chemotherapy use (n = 158 [50.6%]) and Eastern Cooperative Oncology Group (ECOG) performance status were assessed at baseline (median = 3.8 months before death) and patients with progressive metastatic cancer (N = 312) following at least 1 chemotherapy regimen were followed prospectively until death at 6 outpatient oncology clinics in the United States.

Main Outcomes and Measures Patient QOD was determined using validated caregiver ratings of patients’ physical and mental distress in their final week.

Results
Chemotherapy use was not associated with patient survival controlling for clinical setting and patients’ performance status. Among patients with good (ECOG score = 1) baseline performance status, chemotherapy use compared with nonuse was associated with worse QOD (odds ratio [OR], 0.35; 95% CI, 0.17-0.75; P = .01). Baseline chemotherapy use was not associated with QOD among patients with moderate (ECOG score = 2) baseline performance status (OR, 1.06; 95% CI, 0.51-2.21; P = .87) or poor (ECOG score = 3) baseline performance status (OR, 1.34; 95% CI, 0.46-3.89; P = .59).

Conclusions and Relevance
Although palliative chemotherapy is used to improve QOL for patients with end-stage cancer, its use did not improve QOD for patients with moderate or poor performance status and worsened QOD for patients with good performance status. The QOD in patients with end-stage cancer is not improved, and can be harmed, by chemotherapy use near death, even in patients with good performance status.

Sources and more information
  • Chemotherapy Use, Performance Status, and Quality of Life at the End of Life, JAMA Oncology Published online July 23, 2015. doi:10.1001/jamaoncol.2015.2378, July 23, 2015.
  • Chemotherapy for near-death cancer patients ‘does not improve quality of life’, MedicalNewsToday, 24 July 2015.

Probiotics may save Cancer Patients from deadly Chemotherapy and damaging Antibiotics

Induction of intestinal stem cells by R-spondin 1 and Slit2 augments chemoradioprotection

Treating a cancerous tumor is like watering a houseplant with a fire hose – too much water kills the plant, just as too much chemotherapy and radiation kills the patient before it kills the tumor. However, if the patient’s gastrointestinal tract remains healthy and functioning, the patient’s chances of survival increase exponentially… ”

Abstract

NCBI Logo
Cancer breakthrough : Probiotics may save patients from deadly chemotherapy ; antibiotics may cause chemo to be fatal

Cancer research has been righteously and successfully focused on prevention, early detection and identification of specific molecular targets that distinguish the malignant cells from the neighboring benign cells1. However, a major clinical challenge concerns how we can reduce lethal tissue injury caused by intensive chemoradiotherapy during treatment of late-staged metastatic cancers. Here we tested whether induction of adult stem cells repairs chemoradiation-induced tissue injury and prolongs overall survival. We found that intestinal stem cells (ISCs)2 expressed Slit2 and its single-span transmembrane cell-surface receptor Roundabout 1 (Robo1)3,4. Partial genetic deletion of Robo1 decreased intestinal stem cells (ISCs) and caused villus hypotrophy, whereas Slit2 transgene increased ISCs and triggered villus hypertrophy. During lethal dosages of chemoradiation, administering a short pulse of R-spondin 1 (Rspo1; a Wnt agonist)5–14 plus Slit2 reduced ISC loss, mitigated gut impairment and protected animals from death, without concomitantly decreasing tumor sensitivity to chemotherapy. Rspo1 and Slit2 may thus act as therapeutic adjuvants to enhance host tolerance to aggressive chemoradiotherapy for eradicating metastatic cancers.

Sources:
  • Induction of intestinal stem cells by R-spondin 1 and Slit2 augments chemoradioprotection, NCBI, PMCID: PMC3888063, NIHMSID: NIHMS498272, Jul 31, 2013. doi: 10.1038/nature12416
  • Cancer breakthrough: Probiotics may save patients from deadly chemotherapy; antibiotics may cause chemo to be fatal, NaturalNews, 041449, August 01, 2013
  • Gut reaction: Mice survive lethal doses of chemotherapy, MichiganNews, 21613, Jul 31, 2013

Patients receiving Palliative Chemotherapy tied to Worse Deaths, likely in an Intensive Care Unit

Associations between palliative chemotherapy and adult cancer patients’ end of life care and place of death

Abstract

The BMJ logo
The BMJ aims to lead the debate on health, and to engage doctors, researchers and health professionals to improve outcomes for patients.

Objectives
To determine whether the receipt of chemotherapy among terminally ill cancer patients months before death was associated with patients’ subsequent intensive medical care and place of death.

Design
Secondary analysis of a prospective, multi-institution, longitudinal study of patients with advanced cancer.

Setting
Eight outpatient oncology clinics in the United States.

Participants
386 adult patients with metastatic cancers refractory to at least one chemotherapy regimen, whom physicians identified as terminally ill at study enrollment and who subsequently died.

Main outcome measures
Primary outcomes: intensive medical care (cardiopulmonary resuscitation, mechanical ventilation, or both) in the last week of life and patients’ place of death (for example, intensive care unit). Secondary outcomes: survival, late hospice referrals (≤1 week before death), and dying in preferred place of death.

Results
216 (56%) of 386 terminally ill cancer patients were receiving palliative chemotherapy at study enrollment, a median of 4.0 months before death. After propensity score weighted adjustment, use of chemotherapy at enrollment was associated with higher rates of cardiopulmonary resuscitation, mechanical ventilation, or both in the last week of life (14% v 2%; adjusted risk difference 10.5%, 95% confidence interval 5.0% to 15.5%) and late hospice referrals (54% v 37%; 13.6%, 3.6% to 23.6%) but no difference in survival (hazard ratio 1.11, 95% confidence interval 0.90 to 1.38). Patients receiving palliative chemotherapy were more likely to die in an intensive care unit (11% v 2%; adjusted risk difference 6.1%, 1.1% to 11.1%) and less likely to die at home (47% v 66%; −10.8%, −1.0% to −20.6%), compared with those who were not. Patients receiving palliative chemotherapy were also less likely to die in their preferred place, compared with those who were not (65% v 80%; adjusted risk difference −9.4%, −0.8% to −18.1%).

Conclusions
The use of chemotherapy in terminally ill cancer patients in the last months of life was associated with an increased risk of undergoing cardiopulmonary resuscitation, mechanical ventilation or both and of dying in an intensive care unit. Future research should determine the mechanisms by which palliative chemotherapy affects end of life outcomes and patients’ attainment of their goals.

More Information
  • Associations between palliative chemotherapy and adult cancer patients’ end of life care and place of death: prospective cohort study, BMJ 2014; 348:g1219, 04 March 2014.
  • Chemotherapy tied to worse deaths, study finds,
    BostonGlobe, lifestyle/health-wellness, 07 March 2014.
  • Study: Chemotherapy May Lead To Less Peaceful Death,
    CBS, atlanta.cbslocal, 08 March 2014.
  • Chemotherapy proven to cause long, agonizing, suffering death,
    NaturalNews, 044378, 20 March 2014.

The Truth about Chemotherapy and the Cancer Industry

Dan Berger is Cartoonist behind Natural News

The truth about chemotherapy and the cancer industry, a #comics by @HealthRanger on Flickr
The truth about chemotherapy and the cancer industry via @HealthRanger

Patrick Swayze’s death came as a shock to many people. But not to his own cancer doctor: they know that the five-year survival rates of people being treated with chemotherapy for pancreatic cancer are virtually zero. And Swayze was only the latest in a long list of celebrities dying after being treated with chemotherapy and other toxic forms of western medicine…

… The reason so many celebrities are harmed or killed by the cancer industry is quite simple: the cancer industry is a for-profit business. It makes money by treating cancer, not by curing or preventing cancer…

Continue reading: The truth about chemotherapy and the cancer industry by Mike Adams, the Health Ranger.

All our posts about cancer, chemotherapy and screenings.
See more comics.

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