Estimating Gastric Cancer Risk Using DNA Methylation and Lifestyle Data
MedicalXpress Breaking News-and-Events Oct 28, 2023
Gastric cancer is the fourth leading cause of cancer-related mortalities worldwide. Various environmental and lifestyle-related factors, like tobacco and alcohol consumption, are known to contribute to the risk of gastric cancer.
Infection by Helicobacter pylori–a bacterium found in the stomach–is another leading risk factor for the onset of the disease.
H. pylori infection can cause inflammation and exacerbated aberrant DNA methylation in the stomach mucosa. Aberrant DNA methylation due to H. pylori infection can accumulate in the gastric mucosa years before the onset of gastric cancer. DNA methylation in the promoter region of tumour-suppressing genes is known to cause silencing of these genes and eventual carcinogenesis in the tissue.
However, it remains to be confirmed whether DNA methylation caused by H. pylori infection can be used as a marker for future gastric cancer. Further, there are no reports on how the interaction between DNA methylation and lifestyle factors influences the development of gastric cancer.
An international team of researchers, led by Prof. Atsushi Kaneda from Chiba University, Japan, with Prof. Patrick Tan, Senior Vice-Dean for Research & Professor, Cancer & Stem Cell Biology Signature Research Programme, Duke-NUS Medical School and Prof. Khay Guan Yeoh, Kishore Mahbubani Professor in Medicine and Health Policy from the Department of Medicine at the Yong Loo Lin School of Medicine, National University of Singapore, has recently demonstrated how DNA methylation and lifestyle factors interact and influence the risk of gastric tumour development, also known as gastric neoplasia (GN).
The study also involved Dr Genki Usui and other researchers from the following institutions in Japan and Singapore: Chiba University, The University of Tokyo, NTT Medical Center Tokyo, Tokyo University of Science (all in Japan); and Duke-NUS Medical School, the Yong Loo Lin School of Medicine, National University of Singapore, National University Hospital, Tan Tock Seng Hospital, Singapore General Hospital, and Changi General Hospital (all in Singapore).
They collaborated on co-authoring the manuscript published in eBioMedicine. Discussing his motivation to pursue the research, Dr Kaneda, who was formerly a gastrointestinal surgeon, says, "It is, of course, very important to cure patients who have already developed cancer, but I believe it would be more helpful if we can manage cancer risk before cancer development."
The team studied the association between clinical factors and GN development. They examined gastric mucosal biopsy samples collected from asymptomatic subjects who developed GN later or didn't develop GN during a health check-up. Methylation analyses were performed on DNA extracted from these biopsy samples and also from GN tissue, and the mucosae in its vicinity taken from patients who developed GN later.
The data revealed that DNA methylation that highly accumulated in the gastric mucosa many years prior to GN formation was associated with higher GN risk and a shorter period for the onset of disease. Interestingly, the data also showed that methylation levels in the patients' DNAs were linked to H. pylori infection and a lifestyle that involved tobacco and alcohol consumption.
While DNA methylation was determined to be an independent GN risk factor, drinking and smoking were found to amplify the pro-carcinogenic DNA methylation alterations caused by H. pylori.
"The combination of unfavourable lifestyle factors and DNA methylation resulted in a much higher risk of GN development,"
-says Prof Tan.
"Most importantly, when integrated into our analyses, this information accurately reflected the risk of GN and offers the possibility of tailoring management according to the risk of the patient,"
-adds Prof Yeoh.
The study's findings could go a long way in securing a future with lower healthcare costs. Dr. Kaneda is quick to note that stratifying the GN risk across a population opens the door to implementing appropriate cancer prevention strategies at an early stage. Additionally, he is hopeful the findings emphasise how lifestyle choices like tobacco and alcohol consumption impact long-term health.
"We foresee a scenario where high-risk individuals get an early start on gastric cancer interventions. This could be achieved by developing an examination kit that identifies the diagnostic DNA methylation markers and provides a precise GN risk assessment," concludes Drs. Usui and Kaneda.
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Uwezekano wa Kansa ya Matumbo Kutumia Data ya DNA Methylation na Lifestyle - MedicalXpress Breaking News na Matukio Oktoba 28, 2021 Kansa ya Matumbo ni sababu ya nne inayoongoza ya vifo vinavyohusiana na kansa ulimwenguni. Vitu mbalimbali vya mazingira na vya maisha, kama vile kuvuta sigara na kunywa pombe, vinajulikana kuchangia hatari ya kansa ya tumbo. Maambukizi ya Helicobacter pylori - bakteria inayopatikana katika tumbo - ni sababu nyingine kuu ya hatari ya kutokea kwa ugonjwa huo. H. pylori inaweza kusababisha uvimbe na kuharibu methylation DNA katika mucosa ya tumbo. Ugonjwa wa H. pylori unaweza kusababisha kuharibika kwa DNA ya tumbo la tumbo, na kuharibu uwezo wa mwili wa kuhifadhi damu katika tumbo la tumbo. Methylation ya DNA katika eneo la promoter ya jeni la kuzuia uvimbe inajulikana kusababisha kusimamishwa kwa jeni hizi na hatimaye carcinogenesis katika tishu. Hata hivyo, bado ni lazima kuthibitishwa kama DNA methylation inayosababishwa na maambukizo ya H. pylori inaweza kutumika kama alama ya saratani ya tumbo ya baadaye. Kwa kuongezea, hakuna ripoti juu ya jinsi mwingiliano kati ya DNA methylation na mambo ya mtindo wa maisha huathiri maendeleo ya kansa ya tumbo. Timu ya watafiti wa kimataifa, inayoongozwa na Profesa Atsushi Kaneda kutoka Chuo Kikuu cha Chiba, Japan, na Profesa Patrick Tan, Mkurugenzi Mtendaji wa Utafiti wa Utafiti wa Ugonjwa wa Saratani na Biolojia ya Chembe za Msingi, Chuo Kikuu cha Tiba cha Duke-NUS, na Profesa Khay Guanyuan, Profesa wa Tiba na Sera ya Afya wa Kitiba kutoka Chuo Kikuu cha Tiba cha Yonglu Lin, Chuo Kikuu cha Taifa cha Singapore, hivi karibuni walionyesha jinsi methylation ya DNA na mambo ya maisha yanavyoingiliana na kuathiri hatari ya maendeleo ya uvimbe wa tumbo la tumbo. Utafiti huo ulihusisha Dk Genki Usui na watafiti wengine kutoka taasisi zifuatazo nchini Japan na Singapore: Chuo Kikuu cha Chiba, Chuo Kikuu cha Tokyo, Kituo cha Matibabu cha NTT Tokyo, Chuo Kikuu cha Sayansi cha Tokyo (zote nchini Japan), na Chuo Kikuu cha Tiba cha Duke-NUS, Chuo Kikuu cha Tiba cha Yonglu Lin, Chuo Kikuu cha Taifa cha Singapore, Hospitali ya Chuo Kikuu cha Taifa, Hospitali Kuu ya Tan Tock Seng, na Hospitali Kuu ya Changi. Walishirikiana katika kuandika hati iliyochapishwa katika eBioMedicine. "Kama ilivyoelezwa katika makala ya mwisho ya jarida la The Lancet, Kaneda, ambaye hapo awali alikuwa daktari wa upasuaji wa tumbo na matumbo, alisema: ""Ni muhimu sana kutibu wagonjwa ambao tayari wameugua kansa, lakini ninaamini ingekuwa muhimu zaidi ikiwa tunaweza kudhibiti hatari ya kansa kabla ya kuambukizwa." Timu hiyo ilichunguza uhusiano kati ya mambo ya kliniki na maendeleo ya GN. Kwa mfano, uchunguzi wa sampuli za biopsy ya utumbo wa tumbo ulionyesha kwamba watu wasio na dalili walipata ugonjwa wa GND baadaye au hawakupata ugonjwa huo wakati wa uchunguzi wa afya. Uchunguzi wa methylation ulifanywa kwenye DNA iliyotokana na sampuli hizi za biopsy na pia kutoka kwa tishu ya GN na mucosa katika ujirani wake iliyochukuliwa kutoka kwa wagonjwa ambao walipata GN baadaye. Utafiti huo ulionyesha kwamba methylation ya DNA ambayo ilikusanywa sana katika mucosa ya tumbo miaka mingi kabla ya kuundwa kwa GN ilihusishwa na hatari ya GN ya juu na kipindi kifupi cha mwanzo wa ugonjwa. Kwa kushangaza, utafiti huo ulionyesha kuwa viwango vya methylation katika DNA ya wagonjwa walikuwa na uhusiano na maambukizi ya H. pylori na mtindo wa maisha ambao ulihusisha tumbaku na pombe. Wakati DNA methylation iligunduliwa kuwa sababu ya hatari ya GN, kunywa na kuvuta sigara iligunduliwa kuimarisha mabadiliko ya pro-carcinogenic ya DNA methylation inayosababishwa na H. pylori. "Mchanganyiko wa mambo yasiyofaa ya mtindo wa maisha na DNA methylation ilisababisha hatari kubwa zaidi ya maendeleo ya GN", - anasema Profesa Tan. "Hasa, wakati kuunganishwa katika uchambuzi wetu, habari hii kwa usahihi kutafakari hatari ya GN na inatoa uwezekano wa tailoring usimamizi kulingana na hatari ya mgonjwa. """ Matokeo ya utafiti huo yanaweza kusaidia sana kuhakikisha kwamba wakati ujao gharama za huduma za afya zitakuwa chini. Kaneda anaongeza kuwa kupanua hatari ya ugonjwa wa kansa katika idadi ya watu hufungua mlango kwa kutekeleza mikakati sahihi ya kuzuia saratani katika hatua ya mapema. Kwa kuongezea, ana matumaini kwamba matokeo hayo yanasisitiza jinsi chaguzi za mtindo wa maisha kama vile tumbaku na matumizi ya pombe zinavyoathiri afya ya muda mrefu. "Tunaona hali ambapo watu walio hatarini sana huanza mapema matibabu ya kansa ya tumbo. "Hii inaweza kupatikana kwa kuendeleza kit ya uchunguzi ambayo hutambua alama za utambuzi wa DNA methylation na hutoa tathmini sahihi ya hatari ya GN. """ Usui na Kaneda. Exclusive Write-ups & Webinars by KOLs Daily Quiz by Specialty Paid Market Research Surveys Case discussions, News & Journals' summaries