# name
Identification and replication of the interplay of four genetic
                high risk variants for urinary bladder cancer

# metadata.dc.description.abstract[].value
Little is known whether genetic variants identified in
                genome-wide association studies interact to increase bladder
                cancer risk. Recently, we identified two- and three-variant
                combinations associated with a particular increase of bladder
                cancer risk in a urinary bladder cancer case-control series
                (IfADo, 1501 cases, 1565 controls). In an independent
                case-control series (Nijmegen Bladder Cancer Study, NBCS, 1468
                cases, 1720 controls) we confirmed these two- and three-variant
                combinations. Pooled analysis of the two studies as discovery
                group (IfADo-NBCS) resulted in sufficient statistical power to
                test up to four-variant combinations by a logistic regression
                approach. The New England and Spanish Bladder Cancer Studies
                (2080 cases and 2167 controls) were used as a replication
                series. Twelve previously identified risk variants were
                considered.The strongest four-variant combination was obtained
                in never smokers. The combination of rs1014971[AA] near APOBEC3A
                and CBX6, SLC14A1 exon SNP rs1058396[AG,GG], UGT1A intron SNP
                rs11892031[AA], and rs8102137[CC,CT] near CCNE resulted in an
                unadjusted odds ratio of 2.59 (95% CI = 1.93-3.47; P =
                1.87x10-10), while the individual variant odds ratios ranged
                only between 1.11-1.30. The combination replicated in the New
                England and Spanish bladder Cancer Studies (ORunadjusted=1.60,
                95% CI = 1.10-2.33; P = 0.013). The four-variant combination is
                relatively frequent, with 25% in never smoking cases and 11% in
                never smoking controls (total study group: 19% cases, 14%
                controls). In conclusion, we show that four high risk variants
                can statistically interact to confer increased bladder cancer
                risk particularly in never smokers.

# metadata.dc.relation.isformatof[].value
Reproducció del document publicat a:
                http://dx.doi.org/10.1093/carcin/bgx102

# metadata.dc.relation.ispartof[].value
Carcinogenesis, 2017, vol. , num. , p. Ahead of print

# metadata.dc.source[].value
Articles publicats en revistes (ISGlobal)

# metadata.dc.title[].value
Identification and replication of the interplay of four genetic
                high risk variants for urinary bladder cancer