Preconception exposure to mutagens: medical and other exposures to radiation and chemicals

Mulvihill, John J.

doi:10.1007/s12687-012-0104-2

Cited by 12 publications

(8 citation statements)

References 30 publications

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“…Further analysis revealed that older people are at a 3.1 times higher risk when carrying SNP309, which could potentially explain the increased incidence of lung cancer in the elderly (Table 4). It was also observed that men were at 2.24 times higher risk in comparison to female when carrying SNP309, which may reflect the accumulative effects of exposure to higher levels of mutagens [36][37][38]. Many studies have reported that smokers carrying SNP309 are at a significantly increased risk of lung cancer, and our results are in agreement with the studies showing 2.77 times higher risk with smoking, as well [39].…”

Section: Discussionsupporting

confidence: 91%

A cohort study on the association of MDM2 SNP309 with lung cancer risk in Bangladeshi population

Reza

Anamika

Chowdhury

et al. 2020

Korean J Intern Med

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Background/Aims: Bangladesh is a densely populated country with an increased incidence of lung cancer, mostly due to smoking. Therefore, elucidating the association of mouse double minute 2 homolog (MDM2) single nucleotide polymorphism (SNP) 309 (rs2279744) with lung cancer risk from smoking in Bangladeshi population has become necessary. Methods: DNA was extracted from blood samples of 126 lung cancer patient and 133 healthy controls. The MDM2 SNP309 was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), using the restriction enzymes MspA1I. Logistic regression was then carried out to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to estimate the risk of lung cancer. A meta-analysis of SNP309 was also carried out on 12,758 control subjects and 11,638 patient subjects. Results: In multivariate logistic regression, significantly increased risk of lung cancer was observed for MDM2 SNP309 in the dominant model (TG + GG vs. TT: OR, 2.13; 95% CI, 1.29 to 3.53). Stratification analysis revealed that age, sex, obesity, and smoking also increases the risk of lung cancer when carrying the MDM2 SNP309. Our meta-analysis revealed that MDM2 SNP309 was considerably associated with lung cancer in Asian populations (TG + GG vs. TT: OR, 1.32; 95% CI , 1.12 to 1.56; p = 0.019 for heterogeneity). Conclusions: The MDM2 SNP309 was associated with high risk of lung cancer in Bangladeshi and Asian population, particularly with increased age, smoking, and body mass index.

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Section: Discussionsupporting

confidence: 91%

A cohort study on the association of MDM2 SNP309 with lung cancer risk in Bangladeshi population

Reza

Anamika

Chowdhury

et al. 2020

Korean J Intern Med

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“…This is not the case for animal studies, in which mating is continuous regardless of treatment. This difference may help explain the negative results in the human cancer studies 5556…”

Section: Discussionmentioning

confidence: 99%

“…This information is important for counseling cancer survivors planning to have children. Mulvihill55 discusses preconception exposure to mutagens covering medical and other exposures to radiation and chemicals. Winther et al 56.…”

Section: Paternal Exposure To Chemicalsmentioning

confidence: 99%

Male-mediated developmental toxicity

2014

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Male-mediated developmental toxicity has been of concern for many years. The public became aware of male-mediated developmental toxicity in the early 1990s when it was reported that men working at Sellafield might be causing leukemia in their children. Human and animal studies have contributed to our current understanding of male-mediated effects. Animal studies in the 1980s and 1990s suggested that genetic damage after radiation and chemical exposure might be transmitted to offspring. With the increasing understanding that there is histone retention and modification, protamine incorporation into the chromatin and DNA methylation in mature sperm and that spermatozoal RNA transcripts can play important roles in the epigenetic state of sperm, heritable studies began to be viewed differently. Recent reports using molecular approaches have demonstrated that DNA damage can be transmitted to babies from smoking fathers, and expanded simple tandem repeats minisatellite mutations were found in the germline of fathers who were exposed to radiation from the Chernobyl nuclear power plant disaster. In epidemiological studies, it is possible to clarify whether damage is transmitted to the sons after exposure of the fathers. Paternally transmitted damage to the offspring is now recognized as a complex issue with genetic as well as epigenetic components.

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“…Epidemiological evidence including exposure to genotoxins (radiation and chemotherapy) in girls prior to puberty shows that potential damage to primordial follicles by DNA damaging agents does not cause an increase in birth defects in their subsequent offspring. 26 Upon onset of puberty, a 5-to 6-month oocyte maturation cycle is initiated. At any given time, several oocytes are undergoing maturation.…”

Section: Based On Genetic Toxicity Datamentioning

confidence: 99%

Science‐Based Approach to Harmonize Contraception Recommendations in Clinical Trials and Pharmaceutical Labels

Bowman

Bécourt-Lhote

Boulifard

et al. 2022

Clin Pharma and Therapeutics

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This review presents a European Federation of Pharmaceutical Industries and Association/PreClinical Development Expert Group (EFPIA‐PDEG) topic group consensus on a data‐driven approach to harmonized contraception recommendations for clinical trial protocols and product labeling. There is no international agreement in pharmaceutical clinical trial protocols or product labeling on when/if female and/or male contraception is warranted and for how long after the last dose. This absence of consensus has resulted in different recommendations among regions. For most pharmaceuticals, contraception recommendations are generally based exclusively on nonclinical data and/or mechanism. For clinical trials, contraception is the default position and is maintained for women throughout clinical development, whereas appropriate information can justify removing male contraception. Conversely, contraception is only recommended in product labeling when warranted. A base case rationale is proposed for whether or not female and/or male contraception is/are warranted, using available genotoxicity and developmental toxicity data. Contraception is generally warranted for both male and female subjects treated with mutagenic pharmaceuticals. We propose as a starting point that contraception is not typically warranted when the margin is 10‐fold or greater between clinical exposure at the maximum recommended human dose and exposure at the no observed adverse effect level (NOAEL) for purely aneugenic pharmaceuticals and for pharmaceuticals that induce fetal malformations or embryo‐fetal lethality. Other factors are discussed, including contraception methods, pregnancy testing, drug clearance, options for managing the absence of a developmental toxicity NOAEL, drug‐drug interactions, radiopharmaceuticals, and other drug modalities. Overall, we present a data‐driven rationale that can serve as a basis for consistent contraception recommendations in clinical trials and in product labeling across regions.

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Preconception exposure to mutagens: medical and other exposures to radiation and chemicals

Cited by 12 publications

References 30 publications

A cohort study on the association of MDM2 SNP309 with lung cancer risk in Bangladeshi population

A cohort study on the association of MDM2 SNP309 with lung cancer risk in Bangladeshi population

Male-mediated developmental toxicity

Science‐Based Approach to Harmonize Contraception Recommendations in Clinical Trials and Pharmaceutical Labels

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