Genetic determinants of childhood and adult height associated with osteosarcoma risk

Abstract

Background: Although increased height has been associated with osteosarcoma risk in previous epidemiologic studies, the relative contribution of stature during different developmental time-points remains unclear. Furthermore, how genetic determinants of height impact osteosarcoma etiology remains unexplored. Genetic variants associated with stature in previous genome-wide association studies may be biomarkers of osteosarcoma risk. Methods: We tested the associations between osteosarcoma risk and polygenic scores for adult height (416 variants), childhood height, (six variants), and birth length (five variants) in 864 osteosarcoma patients and 1879 controls of European ancestry. Results: Each standard deviation increase in the polygenic score for adult height, corresponding to a 1.7-cm increase in stature, was associated with a 1.10-fold increase in risk of osteosarcoma (95% CI: 1.01–1.19, P= 0.027). Each standard deviation increase in the polygenic score for childhood height, corresponding to a 0.5-cm increase in stature, was associated with a 1.10-fold increase in risk of osteosarcoma (95% CI: 1.01–1.20, P= 0.023). The polygenic score for birth length was not associated with osteosarcoma risk (P=0.11). When adult and childhood height scores were modeled together, they were independently associated with osteosarcoma risk (P=0.037 and 0.043, respectively). An eQTL for CILP2 (cartilage intermediate layer protein 2), rs8103992, was significantly associated with osteosarcoma risk after adjustment for multiple comparisons (OR=1.35, 95% CI: 1.16–1.56, P=7.93×10−5, Padjusted=0.034). Conclusions: Genetic propensity to taller adult and childhood height attainments contributed independently to osteosarcoma risk in our data. These results suggest that the biological pathways affecting normal bone growth may be involved in osteosarcoma etiology.

CILP2 overexpression predicts poor prognosis in colorectal cancer

“…was significantly associated with adult height attainment and osteosarcoma risk after adjustment for multiple comparisons in 864 osteosarcoma cases and 1879 controls of European ancestry [15] . To our best acknowledgement, there were no more reports describing relationship between CILP2 and cancers.…”

“…A significant association was also highlighted between polymorphisms in the CILP gene and osteoarthritis progression [14] . But to our best knowledge, few reports have described the relationship between CILP2 and cancers, except one that reported an expression quantitative trait locus, namely rs8103992, was significantly associated with osteosarcoma risk [15] .…”

CILP2 overexpression correlates with tumor progression and poor prognosis in patients with colorectal cancer in the study of The Cancer Genome Atlas (TCGA) and our cohort analysis

“…However, the molecular mechanism on CLIP2 affecting lipid metabolism is still unclear. According to Chenan Zhang et al, an expression quantitative trait locus for the CILP2 gene, rs8103992, was statistically signi cantly associated with adult height attainment and osteosarcoma risk after adjustment for multiple comparisons in 864 osteosarcoma cases and 1879 controls of European ancestry [16] . To our best acknowledgment, no more reports were describing the relationship between CILP2 and cancers.…”

“…In the preliminary study of TCGA and our cohort analysis, we found that CLIP2 gene showed a tendency of up-expression in colorectal cancer tissues compared with other genes screened by bioinformatics from the TCGA colorectal cancer database. Besides, few reports have described the relationship between CILP2 and cancers, except one that reported an expression quantitative trait locus, namely rs8103992, was statistically signi cantly associated with osteosarcoma risk [16] . In this study, we evaluated CILP2 expression and its correlations with clinicopathological characteristics, such as tumor stages, and overall survival of colorectal cancer patients in the Cancer Genome Altas (TCGA), and furtherly veri ed using immunohistochemistry assay within human colorectal cancer tissues, which may provide a new potential molecular marker for prognostic use of colorectal cancer patients.…”

CILP2 overexpression predicts poor prognosis in colorectal cancer

“…According to Chenan Zhang et al, an expression quantitative trait locus for CILP2 gene, rs8103992, was significantly associated with adult height attainment and osteosarcoma risk after adjustment for multiple comparisons in 864 osteosarcoma cases and 1879 controls of European ancestry [15] . To our best acknowledgement, there were no more reports describing relationship between CILP2 and cancers.…”