Pilot Study on Low Penetrance Breast and Colorectal Cancer Predisposition Markers in Latvia

Abstract

IntroductionIt has not been established whether CHEK2 and NOD2 variants are present in Latvia and whether inherited variation in these genes influences cancer risk in this population.Aim of the studyTo evaluate the role of CHEK2 and NOD2 mutations in breast and colorectal cancers in the population of Latvia.Materials and methodsPeripheral venous blood samples were collected from 185 breast cancer and 235 colorectal cancer consecutive hospital-based cases from 11/2003 to 06/2005. The population control group included blood samples from the clamped distal part of the umbilical cord from 978 consecutive anonymous newborns born between 03/2005 and 08/2005. All cases and controls were tested for the presence of NOD2 3020insC mutation and CHEK2 I157T mutation.ResultsNOD2 3020insC was present in 7.7% (18/235) of CRC cancers, in 9.2% (17/185) of breast cancers and in 7.7% (75/974) of controls. CHEK2 I157T variant was found in 7.6% (14/185) of breast cancer cases, 10.2% (24/235) of colon cancer cases and in 6.4% (63/978) of population controls. NOD2 3020insC variant was associated with increased risk of breast cancer (OR = 2.5, p < 0.05) for cases diagnosed at age between 51 and 60 years. CHEK2 I157T variant was associated with increased risk of colorectal cancer (OR = 1.7, p < 0.05) with the highest OR = 2.0 for cases diagnosed at age >70 yrs.ConclusionsNOD2 3020insC, CHEK2 I157T variants may be associated with increased risk of colorectal and breast cancers in Latvia.

Germline mutations in the CHEK2 kinase gene are associated with an increased risk of bladder cancer

“…Germline CHEK2 mutations have been associated with an increased risk of breast, prostate, colon cancers, thyroid, kidney, low-grade ovarian cancers and lymphomas, but bladder cancer has not been studied extensively. 1,11,[12][13][14][15][16]19,21,24,25 Two previous reports suggest that individuals with mutations in the CHEK2 gene might be at increased risk of bladder cancer. 13,14 To confirm this hypothesis, we have genotyped 416 incident cases of bladder cancer and 3,313 controls for the 4 CHEK2 founder mutations present in the Polish population.…”

The CHEK2 I157T Variant and Colorectal Cancer Susceptibility: A Systematic Review and Meta-analysis

“…Of these, we exclude the articles which the CHEK2 I157T was not variant, not colorectal cancer. Review 8 studies Irmejs et al, 2006;Kilpivaara et al, 2006;Cybulski et al, 2007;Kleibl et al, 2009;Konstantinova et al, 2010;Scharrer et al, 2010;Suchy et al, 2010) examined the association of the CHEK2 variants with CRC susceptibility, and exclude one article (Scharrer et al, 2010) which is not the case-control study. Konstantinova et al, 2010;Suchy et al, 2010) were included in the this meta-analysis.…”

“…Konstantinova et al, 2010;Suchy et al, 2010) were included in the this meta-analysis. In these studies, we identified seven studies of unselected CRC Irmejs et al, 2006;Kilpivaara et al, 2006;Cybulski et al, 2007;Kleibl et al, 2009;Konstantinova et al, 2010;Suchy et al, 2010), five of sporadic CRC (Kilpivaara et al, 2006;Cybulski et al, 2007;Kleibl et al, 2009;Konstantinova et al, 2010;Suchy et al, 2010) and five of familial CRC (Konstantinova et al, 2010;Kilpivaara et al, 2006;Cybulski et al, 2007;Kleibl et al, 2009;Suchy et al, 2010).…”

“…Previously, a meta-analysis has been proved that the 1100delC variant may be an important CRC-predisposing Gene (Xiang et al, 2011). Over the last dacade, considerable epidemiological studies have suggested a role for the CHEK2 I157T variant in CRC susceptibility Irmejs et al, 2006;Kilpivaara et al, 2006;Cybulski et al, 2007;Kleibl Z, et al, 2009;Konstantinova et al, 2010;Suchy et al, 2010). However, the association between this variant and CRC susceptibility is controversial.…”

“…A total of seven studies Irmejs et al, 2006;Kilpivaara et al, 2006;Cybulski et al, 2007;Kleibl et al, 2009;Konstantinova et al, 2010;Suchy et al, 2010) (4,029 cases and 13,844 controls) evaluating the association between the CHEK2 I157T variant and unselected CRC were included. Heterogeneity between studies by the Chi square-test based Q-statistic was not significant (P = 0.762), so the pooled OR was calculated by a fixed-effects model.…”