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Worrisome “quiet” in genes may predict lung cancer

Sept. 18, 2007
Courtesy American Association 
for Cancer Research
and World Science staff

When it’s qui­et—al­most “too qui­et”—in movies, it’s of­ten a sign some­thing is about to go wrong for the good guys. 

The same may be true of genes that guard against lung can­cer, re­search­ers have found. They iden­ti­fied 15 such genes, adding that these could help pre­dict can­cer: if their col­lec­tive ac­ti­vity be­comes too qui­et, it sug­gests oth­er fac­tors in the cell are sup­pres­sing them, a pos­si­ble step to­ward can­cer. 

A test for these genes in nor­mal cells sam­pled via bron­chos­co­py could iden­ti­fy peo­ple at risk for lung can­cer, said James C. Wil­ley of the Un­ivers­ity of To­le­do, Ohio, the lead re­search­er. 

In a study of 49 peo­ple, about half of whom had lung can­cer, Wil­ley and his col­leagues said they iden­ti­fied those pa­tients cor­rectly 96 per­cent of the time. Wil­ley cau­tioned that more, larg­er stud­ies will need to be done to see if such a test can iden­ti­fy fu­ture can­cer suf­fer­ers be­fore they be­come sick.

“Smok­ing causes about 90 per­cent of all lung can­cer cases, yet only about 10 to 15 per­cent of heavy smok­ers will de­vel­op lung can­cer,” said Wil­ley. “We are look­ing for new tech­niques that will al­low us to pick out the 10 to 15 per­cent of in­di­vid­u­als at high­est risk for lung can­cer from the enor­mous pool of cur­rent and form­er smok­ers.”

The Un­ited States alone has more than 40 mil­lion current or form­er heavy smok­ers, he added. And al­though in­creas­ingly pow­er­ful screen­ing tools are avail­a­ble to de­tect lung can­cer ear­ly, it’s very costly to screen all these peo­ple. The new test could lead to bet­ter tar­geted screen­ing, Wil­ley said.

To find which genes are ac­tive in lung can­cer, Wil­ley and his col­leagues look for lev­els of mes­sen­ger RNA tran­script­s—in­struc­tions cop­ied from DNA that di­rect cells to cre­ate spe­cif­ic pro­tein molecules. 

Pre­vi­ously, the re­search­ers had found that genes that pro­tect lung cells from dam­age caused by smoke or tox­ins are poorly reg­u­lat­ed in lung can­cer pa­tients. In the new work, the team tested their the­o­ries by meas­ur­ing “tran­script abun­dance” of 15 genes that en­code pro­tec­tive an­ti­ox­i­dant and DNA re­pair pro­teins in lung air­way cells. Tran­script abun­dance is an in­di­ca­tor of gene ac­ti­vity.

The find­ings were pre­s­ented Sept. 18 at the Amer­i­can As­socia­t­ion for Can­cer Re­search’s In­terna­t­ional Con­fer­ence on Mo­lec­u­lar Di­ag­nos­tics in Can­cer Ther­a­peu­tic De­vel­op­ment, in At­lan­ta, Ga.

* * *

When it’s quiet—almost “too quiet”—in movies, it’s often a sign something is about to go wrong for the good guys. The same may be true of genes that guard against lung cancer, researchers have found. They identified 15 such genes, adding that these could help predict cancer: if enough of their collective activity becomes too quiet, it suggests other factors in the cell are suppresing them, a possible step toward cancer. A test for these genes in normal cells sampled via bronchoscopy could identify people at risk for lung cancer, said James C. Willey of the University of Toledo, Ohio, the lead researcher. In a study of 49 people, about half of whom had lung cancer, Willey and his colleagues said they identified these patients correctly 96 percent of the time. Willey cautioned that more, larger studies will need to be done to see if such a test can identify future cancer sufferers before they become sick. “Smoking causes about 90 percent of all lung cancer cases, yet only about 10 to 15 percent of heavy smokers will develop lung cancer,” said Willey. “We are looking for new techniques that will allow us to pick out the 10 to 15 percent of individuals at highest risk for lung cancer from the enormous pool of current and former smokers.” The United States alone has more than 40 million present or former heavy smokers, he added. And although increasingly powerful screening tools are available to detect lung cancer early, it’s very costly to screen all these people. The new test could lead to better targeted screening, Willey said. To find which genes are active in lung cancer, Willey and his colleagues look for levels of messenger RNA transcripts—instructions copied from DNA that direct cells to create specific protein molecules. Previously, the researchers had found that genes responsible for protecting lung cells from damage caused by smoke or toxins are poorly regulated in lung cancer patients. In the new work, the team tested their theories by measuring “transcript abundance” of 15 genes that encode protective antioxidant and DNA repair proteins in lung airway cells. Transcript abundance is an indicator of gene activity. The findings were presented Sept. 18 in Atlanta at the American Association for Cancer Research’s second International Conference on Molecular Diagnostics in Cancer Therapeutic Development.