Uncommon CHEK2 mis-sense variant and reduced risk of tobacco-related cancers: Case - Control study

P Brennan; J McKay; L Moore; D Zaridze; A Mukeria; N Szeszenia-Dabrowska; J Lissowska; P Rudnai; E Fabianova; D Mates; V Bencko; L Foretova; V Janout; WH Chow; N Rothman; A Chabrier; V Gaborieau; F Odefrey; M Southey; M Hashibe; J Hall; P Boffetta; J Peto; R Peto; RJ Hung

Journal article

Uncommon CHEK2 mis-sense variant and reduced risk of tobacco-related cancers: Case - Control study

P Brennan, J McKay, L Moore, D Zaridze, A Mukeria, N Szeszenia-Dabrowska, J Lissowska, P Rudnai, E Fabianova, D Mates, V Bencko, L Foretova, V Janout, WH Chow, N Rothman, A Chabrier, V Gaborieau, F Odefrey, M Southey, M Hashibe Show all

Human Molecular Genetics | OXFORD UNIV PRESS | Published : 2007

DOI: 10.1093/hmg/ddm127

Abstract

CHEK2 is a key cell cycle control gene encoding a pluripotent kinase that can cause arrest or apoptosis in response to unrepaired DNA damage. We report a large case-control study of a non-functional variant that had previously been expected to increase cancer rates. Four thousand and fifteen cancer patients (2250 lung, 811 squamous upper aero-digestive and 954 kidney) and 3052 controls in central Europe were genotyped for the mis-sense variant rs17879961 (replacement of T by C), which changes an amino acid (I157T) in an active site of the gene product. The heterozygous (T/C) genotype was associated with a highly significantly lower incidence of lung cancer than the common T/T genotype [relat..

View full abstract