Ran­dom DNA mis­takes ac­count for most mu­ta­tions in tu­mours, says study

New Straits Times - - World -

WHAT causes cancer? A new study pub­lished on Thurs­day sug­gests that cells make ran­dom mis­takes while di­vid­ing, ac­count­ing for most of the mu­ta­tions in tu­mours, rather than fam­ily his­tory or en­vi­ron­men­tal fac­tors.

The re­port in the jour­nal, Science, was au­thored by the same team that led a con­tro­ver­sial study in Jan­uary 2015 that said ran­dom DNA mu­ta­tions, or in other words just “bad luck”, was of­ten to blame for cancer.

This time, they ex­panded their math­e­mat­i­cal model based on DNA se­quenc­ing and epi­demi­o­logic data to 69 coun­tries world­wide.

“Two-thirds of the mu­ta­tions that oc­cur in can­cers are due to the mis­takes that cells make when they di­vide,” co-au­thor Bert Vo­gel­stein, co-di­rec­tor of the Lud­wig Cen­tre at the Johns Hop­kins Uni­ver­sity Kim­mel Cancer Cen­ter, said.

En­vi­ron­ment was a fac­tor in 29 per cent of the mu­ta­tions in cancer, while hered­ity ac­counted for five per cent, ac­cord­ing to the study.

“Ev­ery time a per­fectly nor­mal cell di­vides, it makes sev­eral mis­takes— mu­ta­tions. Most of the time, th­ese mu­ta­tions are harm­less. That is the usual sit­u­a­tion and that is ‘good luck’ in our para­phrase.

“But, oc­ca­sion­ally, they oc­cur in a cancer-driver gene. That is ‘bad luck’,” Vo­gel­stein said.

The goal of the study was to bet­ter un­der­stand th­ese mu­ta­tions so that bet­ter ways of de­tect­ing cancer early can be de­vel­oped.

The study shines a spot­light on can­cers that will oc­cur no mat­ter how per­fect the en­vi­ron­ment, and may al­le­vi­ate the guilt some pa­tients face when they are di­ag­nosed.

“Th­ese copy­ing mis­takes are a po­tent source of cancer mu­ta­tions that his­tor­i­cally have been sci­en­tif­i­cally un­der­val­ued,” said co-au­thor Cristian To­masetti, as­sis­tant pro­fes­sor of bio­statis­tics at the Johns Hop­kins Kim­mel Cancer Cen­tre.

How­ever, he urged peo­ple to avoid known risk fac­tors for cancer, such as smok­ing and too much sun ex­po­sure.

“We need to con­tinue to en­cour­age peo­ple to avoid en­vi­ron­men­tal agents and lifestyles that in­crease their risk of de­vel­op­ing cancer mu­ta­tions.”

Vo­gel­stein con­curred, stress­ing that the lat­est re­search was “in per­fect ac­cord with epi­demi­o­log­i­cal es­ti­mates that 42 per cent of can­cers can be pre­vented, and every­one should ad­here to those preven­tion guide­lines”.

For lay peo­ple, the take­away mes­sage is that many cases of cancer can be pre­vented, even though many can­cer­ous mu­ta­tions can­not.

“De­spite the role of the ran­dom repli­ca­tion com­po­nent in pro­duc­ing mu­ta­tions, you could re­duce the cancer risk hugely for many types of cancer by get­ting rid of the en­vi­ron­men­tal and/or hered­i­tary causes,” he said.

Lawrence Young, di­rec­tor of the Cancer Re­search Cen­tre at the Uni­ver­sity of War­wick in Eng­land, said the study “con­trib­utes to the con­tro­ver­sial de­bate”.

How­ever, any math­e­mat­i­cal model that at­tempts to ac­count for cancer risks must take in a va­ri­ety of ex­ter­nal fac­tors.

“So, while this study is use­ful in at­tempt­ing to in­te­grate epi­demi­o­log­i­cal and genome se­quenc­ing data, the mes­sage is com­plex and does not di­min­ish the need to fo­cus on im­proved ap­proaches to pri­mary and sec­ondary cancer preven­tion.”

Healthy cells nat­u­rally make mis­takes when they mul­ti­ply.

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