Worrisome “quietâ€

[Christine]

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.