Archive for month: February, 2024

A recent study published in the Human Reproduction found the familial multicancer patterns among men with azoospermia and severe oligozoospermia by offering valuable insights into the heterogeneity of cancer risk within these subfertility groups. The research utilized extensive population data to analyze cancer risks among families of subfertile men.

This study involved a retrospective cohort of 786 subfertile men including azoospermic and severely oligozoospermic individuals who were matched with fertile population controls. The research identified family members up to third-degree relatives for both subfertile men and controls with over 337,754 individuals over a period from 1966 to 2017.

The findings revealed distinct familial cancer patterns in the azoospermia and severe oligozoospermia cohorts that indicates variations in cancer risk not only between different types of subfertility but also within subfertility types. Also, this study identified significant increases in cancer risks in specific types among both cohorts when compared to control families.

In the azoospermia cohort, the increased risks were observed for bone and joint cancers, soft tissue cancers, uterine cancers, Hodgkin lymphomas, and thyroid cancer. The severe oligozoospermia cohort showed higher risk for colon cancer, bone and joint cancers and testis cancer, along with a decreased risk of esophageal cancer.

This analysis identified multiple clusters of familial multicancer patterns within both cohorts, with some expressing elevated cancer risks across various types. Certain clusters expressed increased odds of cancer diagnoses at young ages by including adolescent and young adult diagnoses, as well as pediatric cancer diagnoses.

Despite the strengths of the study, including comprehensive population data, the outcomes acknowledge limitations such as the lack of semen measures for fertile men and the absence of information on medical comorbidities and lifestyle factors. The implications of these findings are significant by offering a new opportunity for focused gene discovery and environmental risk factor studies.

Source:

Ramsay, J. M., Madsen, M. J., Horns, J. J., Hanson, H. A., Camp, N. J., Emery, B. R., Aston, K. I., Ferlic, E., & Hotaling, J. M. (2024). Describing patterns of familial cancer risk in subfertile men using population pedigree data. Human Reproduction, dead270. https://doi.org/10.1093/humrep/dead270

Belgium: Findings from the ADVOR trial have revealed the safety and efficacy of acetazolamide for treating congestion across the entire range of renal function; more pronounced beneficial effects are seen in patients with a lower estimated glomerular filtration rate (eGFR).

Cigarette smoke exposure is associated with the development and severity of chronic obstructive pulmonary disease, or COPD, which is the third leading cause of death worldwide.

Cigarette smoke contains 2 to 3 micrograms of cadmium, a highly toxic metal and environmental pollutant, per cigarette. Burning tobacco releases cadmium oxide that can be adsorbed onto microparticles in smoke that travel deep into the lungs. Furthermore, the body is not able to remove cadmium, which accumulates in longtime smokers.

In a Scientific Reports study, University of Alabama at Birmingham researchers show how a low dose of cadmium produces a deleterious stress in lung epithelial cells, and their findings highlight potential therapeutic targets to be explored in cadmium-exposure and subsequent lung injury.

The research, led by Veena Antony, M.D., a professor in the UAB Department of Medicine, focuses on microRNA-381, and the expression of a chloride channel gene called ANO1 in lung tissue samples and airway epithelial cells. ANO1 helps produce mucus in the airway; but overproduction of mucus in chronic lung disease can lead to airway thickening and mucus blockage, adding to severity of the disease. Thus, overexpression of ANO1 can exacerbate COPD.

The UAB researchers compared lung tissue samples from nine “never” smokers, who had zero history of cigarette smoking, and lung tissue samples from 13 “ever” smokers with COPD who had a history of smoking that ranged from 15 to 25 pack years per person. One pack year is generally defined as smoking one pack of cigarettes a day for one year. The researchers found that “ever” smokers, in contrast to “never” smokers, had upregulated ANO1 expression in airway epithelial cells.

Similarly, airway epithelial cells in a bronchoalveolar lavage fluid from one non-COPD subject and one smoker with COPD showed greater ANO1 expression in the COPD-subject cells.

The researchers next tested the direct effect of very low doses of cadmium on normal human airway epithelial cells. These cells were grown on an air-liquid interface that allows the airway cells to differentiate normally. Two weeks of exposure to 0.5 or 1.0 micromolar cadmium chloride in the liquid layer increased expression of ANO1 12 to 14 times.

MicroRNAs have the ability to downregulate expression of a gene by direct interaction with that gene’s mRNA sequence. The UAB team used computer software analysis to identify microRNA-381 as the microRNA with most interaction with ANO1 mRNAs, suggesting that microRNA-381 is a negative regulator of ANO1. Some heavy metals are known to negatively regulate microRNAs.

Antony and colleagues used a synthetic inhibitor for microRNA-381 to inhibit the expression of microRNA-381 in primary human airway epithelial cells from subjects with COPD, and found that ANO1 expression was upregulated significantly. In contrast, adding a microRNA-381-mimic-a synthetic RNA that acts like microRNA-381 to increase the amount of negative regulation-to those cells decreased ANO1 expression. These results strengthened the premise of the UAB researchers that cadmium negatively regulates microRNA-381 expression to upregulate ANO1 expression in airway epithelial cells.

Lastly, researchers found that, even when primary human airway epithelial cells from subjects with COPD were also exposed to 1 micromolar cadmium chloride, the microRNA-381 inhibitor still upregulated ANO1 and the mimic still downregulated ANO1.

“Our observations from experiments involving low-dose cadmium-exposure of epithelial cells suggest that ANO1 is a direct target for miR-381, which is downregulated upon low-dose cadmium exposure,” Antony said. “Thus, cigarette-induced cadmium-toxicity may alter cellular homeostasis mechanisms at very low concentrations, and cadmium-exposure in a person with an existing pulmonary condition can have an additive or adverse effect with increased susceptibility toward infections and environmental allergens.

“This interaction of cadmium, microRNA-381 and ANO1 suggests that microRNAs may act as potential therapeutic targets to be explored further in cadmium-exposure and subsequent lung injury.”

Reference:

Singh, P., Li, F.J., Dsouza, K. et al. Low dose cadmium exposure regulates miR-381–ANO1 interaction in airway epithelial cells. Sci Rep 14, 246 (2024). https://doi.org/10.1038/s41598-023-50471-z.

Annual breast cancer screening beginning at age 40 and continuing to at least age 79 results in the highest reduction in mortality with minimal risks, according to a new study published today in Radiology, a journal of the Radiological Society of North America (RSNA).

Breast cancer is the second most common cause of cancer death for women in the U.S. Despite research demonstrating that consistent participation in screening mammography can reduce breast cancer deaths by 40%, only 50% or less of eligible women actually participate in annual screening.

“There is an ongoing debate over the recommendations for breast cancer screening, specifically about when to start and the frequency of screening,” said lead researcher Debra L. Monticciolo, M.D., professor of radiology at Dartmouth Geisel School of Medicine in Hanover, New Hampshire.

Dr. Monticciolo said a recommendation by the U.S. Preventive Services Task Force (USPSTF) in 2009 to screen every other year, or biennially, beginning at age 50 resulted in a nationwide decline in screening participation. The USPSTF drafted new recommendations in 2023, suggesting women participate in biennial screening between 40 and 74. The American College of Radiology, the Society of Breast Imaging and the National Comprehensive Cancer Network recommend annual screening for women at average risk for breast cancer beginning at age 40 and continuing as long as the woman is in good health.

In the study, Dr. Monticciolo and colleagues performed a secondary analysis of Cancer Intervention and Surveillance Modeling Network (CISNET) 2023 median estimates of breast cancer screening outcomes. CISNET modeling data gives researchers the opportunity to estimate the outcomes of screening at various frequencies and starting ages using U.S. data.

The researchers compared the benefits of screening, including mortality reduction, life years gained, breast cancer deaths averted, and its risks-including benign, or unnecessary, biopsies and recall rates-for four different scenarios: biennial screening of women 50-74 (the longstanding USPSTF recommendation), biennial screening of women 40-74 (the task force’s new draft recommendation), annual screening 40-74, and annual screening 40-79. CISNET does not offer modeling past age 79.

The review of CISNET estimates showed that annual screening of women 40-79 with either digital mammography or tomosynthesis showed a mortality reduction of 41.7%. Biennial screening of women 50-74 and 40-74 showed mortality reduction of 25.4% and 30%, respectively. Annual screening of women 40-79 years showed the lowest per mammogram false-positive screens (6.5%) and benign biopsies (0.88%) compared to other screening scenarios.

“The biggest takeaway point of our study is that annual screening beginning at 40 and continuing to at least age 79 gives the highest mortality reduction, the most cancer deaths averted, and the most years of life gained,” Dr. Monticciolo said. “There’s a huge benefit to screening annually until at least 79 and even more benefit if women are screened past 79.”

Dr. Monticciolo said that although the USPSTF uses CISNET modeling to formulate its recommendations, it refers to recall rates and benign biopsies as harms, rather than risks.

“To balance the harms and benefits of screening mammography, they’re willing to give up some mortality benefit to avoid women being recalled for additional imaging and benign biopsies,” she said.

According to the researchers’ analyses, the chance of a woman having a benign biopsy following annual screening is less than 1%, and all recall rates for screening mammography are under 10%. When screening is performed annually with tomosynthesis, the recall rate decreases to 6.5%.

“The risks of screening are non-lethal and manageable for most women,” she said. “But advanced breast cancer is often lethal. Breast cancer is easier to treat if it’s found earlier; we’re able to spare women extra surgeries and chemotherapy. It’s just a better idea to shift to early detection, and that’s what screening does.”

Dr. Monticciolo said she hopes that her study will add to the body of literature that supports annual screening beginning at age 40 as the best way to diagnose cancer early.

“This paper is important because it shows once again that there’s a tremendous increase in mortality benefit by screening annually between the ages of 40-79, and that the chances of experiencing harm are low on a per-exam basis,” she said. “It comes down to valuing women’s lives. I am hoping that primary care physicians see that risks of screening are manageable, and the benefits are tremendous. We need to do this for women.”

Reference:

Debra L. Monticciolo , R. Edward Hendrick, Mark A. Helvie, Outcomes of Breast Cancer Screening Strategies Based on Cancer Intervention and Surveillance Modeling Network Estimates, Radiology, https://doi.org/10.1148/radiol.232658.

Bonding of second molars enhances the outcome of non-extraction fixed orthodontic treatment, finds a study published in the Angle Orthodontist.