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Smoking and mosaic Y chromosome loss
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A new study by Lars Forsberg (Uppsala University, Sweden) and colleagues has shown that smoking is associated with mosaic loss of chromosome Y. Earlier this year, the same research group showed that this kind of mosaicism, so-called because of the interspersing of normal cells with those without the Y chromosome, was associated with an increased risk of cancer in all organs and tissues. “The finding that smoking induces loss of chromosome Y thus links a preventable risk factor with the most common human mutation”, they wrote. The investigators examined blood samples from 6014 Swedish men drawn from three prospective cohorts. Loss of chromosome Y affected 4373 (7·5%), 1153 (12·6%), and 488 (15·6%) of the men in the respective cohorts, and was particularly common among men older than 70 years. The loss was
strongly associated with smoking (odds ratios ranged from 2·4–4·3). The results might help to explain why men have an increased incidence and mortality from most non-sex specific cancers. “It could be that the loss of the Y chromosome suppresses immunosurveillance”, explained Forsberg. Perhaps the Y chromosome equips the immune cells to fight cancer, and its loss leaves men more vulnerable to cancer. If so, this would cohere with the theory that women have less cancer than do men because their immune systems are stronger. “It is very interesting, but it is unproven”, said David Phillips (Kings College London, UK). “It was still a minority of cells that did not have the Y chromosome, so while it is statistically significant, it may not be biologically significant”. The researchers did not find a difference in loss of Y chromosome between those who had stopped
smoking and those who had never smoked. This finding suggests that as the blood cells without the Y chromosome die out, they are replenished by fully functional cells and that the immune system can recover from some of the ravages of smoking. “It might be one component of a protective mechanism that is restored by stopping smoking”, offered Phillips. However, this remains speculative, and Forsberg hopes to resolve some of the unanswered questions. “We have hypothesised that this is all connected to the tumour immunosurveillance process”, he told The Lancet Oncology. “There are certain cells in the immune system that are involved in this process and we are investigating them in cohorts to pinpoint which of these cells are actually failing when you get cancer”.
Science Photo Library
Smoking and mosaic Y chromosome loss
Published Online December 16, 2014 http://dx.doi.org/10.1016/ S1470-2045(14)71177-5 For Fosberg and colleagues’ study see Science 2014; published online Dec 4. DOI:10.1126/science.1262092
Talha Khan Burki
POT1: a genetic link for familial glioma Mutations in POT1 are associated with familial glioma, new research suggests. Familial glioma accounts for less than 5% cases of glioma, the most common type of brain tumour that includes various subtypes. Matthew Bainbridge and colleagues noted that previous studies did not properly show the genetic contribution to familial glioma. The researchers studied 435 families with glioma from 14 centres in Sweden, Denmark, the USA, the UK, and Israel. Whole exome sequencing was done in 90 individuals from 55 families. The investigators identified two different mutations in POT1, which belongs to the telomere shelterin complex, in two families (family A and B). In family A, six individuals had POT1 mutation, of whom three developed glioma. In family B, also www.thelancet.com/oncology Vol 16 January 2015
six individuals had POT1 mutation and two developed glioma. The researchers validated their findings in a cohort of 264 patients with glioma from 246 families, and identified, in one family (family C), the third protein-changing mutation in POT1. In families with POT1 mutations, the researchers reported that the affected members suffered from a particular type of glioma, oligodendroglioma, which is substantially sensitive to irradiation. “The association between familial glioma and the POT1 mutation is strong in our data, but it still needs to be validated,” commented investigator Melissa Bondy (Baylor College of Medicine, Houston, TX, USA). “We would love [to study] more families, especially those with oligodendroglioma, the type of glioma most associated with POT1”,
she added. According to Rimas Lukas (University of Chicago, Chicago, Illinois, USA), the study provides “a clearer appreciation of the genetic risk factors for developing oligodendrogliomas.” “This will assist in the genetic counselling of patients and families with gliomas and other familial cancers harbouring germline mutations in the same gene, such as melanoma”, he added. “It would be reasonable to test for POT1 in a family in whom several members have developed oligodendrogliomas”, commented Jeffrey Raizer (Northwestern Brain Tumor Institute, Chicago, IL, USA). However, he added that it was important to note that “this study does not mean that if a patient develops a glioma, all family members are at risk of developing a glioma”.
Published Online December 16, 2014 http://dx.doi.org/10.1016/ S1470-2045(14)71178-7 For Bainbridge and colleagues’ study see J Natl Cancer Inst 2014; 107: dju384
Sanjeet Bagcchi e12
A new study by Lars Forsberg (Uppsala University, Sweden) and colleagues has shown that smoking is associated with mosaic loss of chromosome Y. Earlier this year, the same research group showed that this kind of mosaicism, so-called because of the interspersing of normal cells with those without the Y chromosome, was associated with an increased risk of cancer in all organs and tissues. “The finding that smoking induces loss of chromosome Y thus links a preventable risk factor with the most common human mutation”, they wrote. The investigators examined blood samples from 6014 Swedish men drawn from three prospective cohorts. Loss of chromosome Y affected 4373 (7·5%), 1153 (12·6%), and 488 (15·6%) of the men in the respective cohorts, and was particularly common among men older than 70 years. The loss was
strongly associated with smoking (odds ratios ranged from 2·4–4·3). The results might help to explain why men have an increased incidence and mortality from most non-sex specific cancers. “It could be that the loss of the Y chromosome suppresses immunosurveillance”, explained Forsberg. Perhaps the Y chromosome equips the immune cells to fight cancer, and its loss leaves men more vulnerable to cancer. If so, this would cohere with the theory that women have less cancer than do men because their immune systems are stronger. “It is very interesting, but it is unproven”, said David Phillips (Kings College London, UK). “It was still a minority of cells that did not have the Y chromosome, so while it is statistically significant, it may not be biologically significant”. The researchers did not find a difference in loss of Y chromosome between those who had stopped
smoking and those who had never smoked. This finding suggests that as the blood cells without the Y chromosome die out, they are replenished by fully functional cells and that the immune system can recover from some of the ravages of smoking. “It might be one component of a protective mechanism that is restored by stopping smoking”, offered Phillips. However, this remains speculative, and Forsberg hopes to resolve some of the unanswered questions. “We have hypothesised that this is all connected to the tumour immunosurveillance process”, he told The Lancet Oncology. “There are certain cells in the immune system that are involved in this process and we are investigating them in cohorts to pinpoint which of these cells are actually failing when you get cancer”.
Science Photo Library
Smoking and mosaic Y chromosome loss
Published Online December 16, 2014 http://dx.doi.org/10.1016/ S1470-2045(14)71177-5 For Fosberg and colleagues’ study see Science 2014; published online Dec 4. DOI:10.1126/science.1262092
Talha Khan Burki
POT1: a genetic link for familial glioma Mutations in POT1 are associated with familial glioma, new research suggests. Familial glioma accounts for less than 5% cases of glioma, the most common type of brain tumour that includes various subtypes. Matthew Bainbridge and colleagues noted that previous studies did not properly show the genetic contribution to familial glioma. The researchers studied 435 families with glioma from 14 centres in Sweden, Denmark, the USA, the UK, and Israel. Whole exome sequencing was done in 90 individuals from 55 families. The investigators identified two different mutations in POT1, which belongs to the telomere shelterin complex, in two families (family A and B). In family A, six individuals had POT1 mutation, of whom three developed glioma. In family B, also www.thelancet.com/oncology Vol 16 January 2015
six individuals had POT1 mutation and two developed glioma. The researchers validated their findings in a cohort of 264 patients with glioma from 246 families, and identified, in one family (family C), the third protein-changing mutation in POT1. In families with POT1 mutations, the researchers reported that the affected members suffered from a particular type of glioma, oligodendroglioma, which is substantially sensitive to irradiation. “The association between familial glioma and the POT1 mutation is strong in our data, but it still needs to be validated,” commented investigator Melissa Bondy (Baylor College of Medicine, Houston, TX, USA). “We would love [to study] more families, especially those with oligodendroglioma, the type of glioma most associated with POT1”,
she added. According to Rimas Lukas (University of Chicago, Chicago, Illinois, USA), the study provides “a clearer appreciation of the genetic risk factors for developing oligodendrogliomas.” “This will assist in the genetic counselling of patients and families with gliomas and other familial cancers harbouring germline mutations in the same gene, such as melanoma”, he added. “It would be reasonable to test for POT1 in a family in whom several members have developed oligodendrogliomas”, commented Jeffrey Raizer (Northwestern Brain Tumor Institute, Chicago, IL, USA). However, he added that it was important to note that “this study does not mean that if a patient develops a glioma, all family members are at risk of developing a glioma”.
Published Online December 16, 2014 http://dx.doi.org/10.1016/ S1470-2045(14)71178-7 For Bainbridge and colleagues’ study see J Natl Cancer Inst 2014; 107: dju384
Sanjeet Bagcchi e12