| Abstract: | Alterations in stromal tissue components can inhibit or promote epithelial
tumorigenesis. Decorin (DCN) and lumican (LUM)
show reduced stromal expression in serous epithelial ovarian cancer (sEOC). We
hypothesized that common variants in these genes associate with risk.
Associations with sEOC among Caucasians were estimated with odds ratios (OR)
among 397 cases and 920 controls in two U.S.-based studies (discovery set), 436
cases and 1,098 controls in Australia (replication set 1) and a consortium of 15
studies comprising 1,668 cases and 4,249 controls (replication set 2). The
discovery set and replication set 1 (833 cases and 2,013 controls) showed
statistically homogeneous (Pheterogeneity≥0.48) decreased risks of
sEOC at four variants: DCN rs3138165, rs13312816 and rs516115,
and LUM rs17018765 (OR = 0.6 to 0.9;
Ptrend = 0.001 to 0.03). Results from
replication set 2 were statistically homogeneous
(Pheterogeneity≥0.13) and associated with increased risks at
DCN rs3138165 and rs13312816, and LUM
rs17018765: all ORs = 1.2; Ptrend≤0.02. The
ORs at the four variants were statistically heterogeneous across all 18 studies
(Pheterogeneity≤0.03), which precluded combining. In post-hoc
analyses, interactions were observed between each variant and recruitment period
(Pinteraction≤0.003), age at diagnosis
(Pinteraction = 0.04), and year of diagnosis
(Pinteraction = 0.05) in the five studies
with available information (1,044 cases, 2,469 controls). We conclude that
variants in DCN and LUM are not directly
associated with sEOC, and that confirmation of possible effect modification of
the variants by non-genetic factors is required. |
