The cardiorespiratory fitness of survivors of childhood acute lymphoblastic leukemia is 22 per cent worse than that of Canadians generally, and genetics might play a role. Credit: CC0 Public Domain. إن اللياقة القلبية التنفسية للناجين من الابيضاض اللمفاوي الحاد في الطفولة أسوأ بنسبة 22 % من الكنديين عموماً، وقد تؤدي الوراثة دوراً في ذلك. حقوق نشر الصورة محفوظة: CC0 Public Domain.
The cardiorespiratory fitness of survivors of childhood acute lymphoblastic leukemia is 22 per cent worse than that of Canadians generally, and genetics might play a role, an UdeM scientist finds.
Nearly 90 per cent of children with acute lymphoblastic leukemia (ALL) survive, yet the same treatments that save their life can adversely affect their quality of life and cardiorespiratory fitness health. In fact, the cardiorespiratory fitness of ALL survivors can be significantly worse than a sample of healthy Canadians, despite similar levels of physical activity.
Maxime Caru, an Université de Montréal doctoral student in kinesiology, demonstrates that a group of genes known as “trainability genes” are linked to cardiorespiratory fitness.
Caru’s study also demonstrates that a group of genes known as “trainability genes” are linked to cardiorespiratory fitness. He presented the findings of this research at the American College of Sports Medicine’s Annual Meeting in Orlando, Florida.
“Previous work by UdeM's Laboratory of physiopathology of the exercise, where I carried out my research, had suggested that ALL survivors weren't following recommendations for physical activity,” said Caru, who is also a researcher at the CHU Sainte-Justine Research Centre.
"But until now no Canadian study had compared the cardiorespiratory fitness of ALL survivors against the healthy population.”
Women affected more than men
In his study, which compares a cohort of 250 survivors of childhood ALL to 825 healthy Canadians, Caru found that the cardiorespiratory fitness of survivors was 22 per cent worse than the healthy population, with a maximum oxygen uptake of nearly 9.2 mL.kg-1.min-1.
He also noted that moderate- to high-intensity physical activity did not improve cardiorespiratory fitness as much among survivors, and that this was particularly true among female survivors.
The reduction in cardiorespiratory fitness can only be partly attributed to ALL treatments and other environmental factors, Caru believes.
Previous studies have found links between trainability genes and changes in cardiorespiratory fitness among healthy people who perform physical activity. To better analyse those links, in the second part of the study, Caru and his colleagues ran genetic association analyses between trainability genes (238 genes, including 134 common variants and 1,225 rare variants) and the cardiorespiratory fitness of ALL survivors.
Genetically linked to 'trainability' genes
For the first time, they were able to show that poor cardiorespiratory fitness in survivors is genetically linked to trainability genes, especially the TTN gene. This gene provides cells with instructions for making a protein known as titin that is key to skeletal muscles (those used to move the body) and heart muscles. Furthermore, female survivors with poor cardiorespiratory fitness showed the strongest genetic associations with three other trainability genes: LEPR, IGFBP 1 and ENO3.
While the study’s findings aren't good news, they do “provide valuable information on genetic associations with poor cardiorespiratory fitness among ALL survivors,” said UdeM kinesiology professor Daniel Curnier, who directed the study.
“Although the study revealed that ALL survivors are doubly burdened by their illness and related treatments, it also provided additional evidence of the benefits of physical activity for childhood cancer treatment. In light of this, ALL survivors need better support to engage in physical activity and ensure they get the most out of it and improve their cardiorespiratory fitness.”
Added Caru: “The study will help kinesiologists develop more personalized plans and effective preventative strategies for ALL survivors to minimize long-term health effects.”
Materials provided by Université de Montréal.
ينجو حوالي ٩٠% من الأطفال المصابين بالابيضاض اللمفاوي الحاد ALL، ولكنّ الدراسات السابقة أظهرت أنّ هؤلاء الناجين لم يكونوا يتبعون توصيات النشاط الفيزيائي، ورغم أنّ علاجات ALL قد تؤثر في نوعية الحياة واللياقة القلبية الرئوية؛ إلا أنّ العلماء أرادوا معرفة ما إن كان لجينات تدعى بجينات القابلية للتمرين trainability genes علاقة باللياقة القلبية الرئوية للناجين من الجمهرة الكندية.
من أجل ذلك؛ قارن باحثون ٢٥٠ طفلاً ناجياً من ALL مع ٨٢٥ من الأصحاء الكنديين، وقد أظهرت النتائج أنّ اللياقة القلبية الرئوية كانت أخفض بنسبة ٢٢% لدى الناجين مقارنة بالأصحاء، كما أنّ التمارين الفيزيائية متوسطة إلى عالية الشدة فشلت في تحسين هذه اللياقة لدى الناجين كما تفعل مع الأصحاء، وخاصة لدى الناجيات الإناث. وبإجراء تحليل الارتباط الجيني؛ تبين أنّ ضعف اللياقة القلبية الرئوية للناجين كان مرتبطاً جينياً بجينات القابلية للتمرين وعلى وجه الخصوص بجين يدعى TTN gene، وهو جين مسؤول عن تصنيع بروتين titin الهام للعضلات الهيكلية والقلبية، كما أنّ الناجيات الإناث ضعيفات اللياقة القلبية الرئوية أبدين ارتباطاً جينياً قوياً بكل من جينات LEPR و IGFBP 1 و ENO3، وجميعها من جينات القابلية للتمرين.
وتؤكد هذه الدراسة على أهمية الانخراط في النشاط الفيزيائي للناجين لدعم لياقتهم القلبية الرئوية، كما ستساعد نتائجها أخصائيي الحركة في وضع خطط مخصصة وفعالة لهؤلاء الناجين.
أجري البحث في: University of Montreal
نشر في: BMC Cancer
Related organization: Université de Montréal