Experimental and observational studies in humans and animals suggest that insulin-like growth factor 1 (IGF1) and its principal binding protein, IGFBP3, may influence breast cancer susceptibility. We have examined the association of nine and four single nucleotide polymorphisms (SNPs) in the IGF1 gene and in the IGFBP3 genes, respectively, with circulating levels of their gene products in a population-based study of 600 middle-aged men and women, and in a breast cancer case-control study, comprised 4647 cases and 4564 controls. All study participants are from the East Anglian region of UK. SNPs were specifically chosen to tag all other known SNPs in each gene. Several SNPs in each gene are associated both with circulating levels of their respective proteins and with risk of breast cancer. In particular, the c allele of IGF1 SNPrs1520220 is associated with increased circulating IGF1 (r2=2.1%, P-trend=0.003) in females and an increased risk of breast cancer: odds ratio (OR) (cc/gg)=1.41; 95% confidence intervals (95% CI) 1.11-1.79, P-trend=0.03. The a allele of IGFBP3 SNP rs2854744 is associated with increased circulating IGFBP3 (r2=9.7%, P<10(-9)) and a decreased risk of breast cancer: OR (aa/cc)=0.87; 95% CI 0.77-0.99, P=0.03. Our data indicate that common variants in the IGF1 and IGFBP3 genes are associated with differences in circulating levels of IGF1 and IGFBP3 and with breast cancer risk. More specifically and consistent with experimental models, our data suggest that higher IGF1 levels may increase the risk of breast cancer but higher IGFBP3 levels may be protective.
Air pollution exposure has been shown to be associated with an increased risk of specific cancers. This study investigated whether the number and incidence of the most common cancers in Saudi Arabia were associated with urban air pollution exposure, specifically NO2. Overall, high model goodness of fit (GOF) was observed in the Eastern, Riyadh and Makkah regions. The significant coefficients of determination (r2) were higher at the regional level (r2 = 0.32–0.71), weaker at the governorate level (r2 = 0.03–0.43), and declined slightly at the city level (r2 = 0.17–0.33), suggesting that an increased aggregated spatial level increased the explained variability and the model GOF. However, the low GOF at the lowest spatial level suggests that additional variation remains unexplained. At different spatial levels, associations between NO2 concentration and the most common cancers were marginally improved in geographically weighted regression (GWR) analysis, which explained both global and local heterogeneity and variations in cancer incidence. High coefficients of determination were observed between NO2 concentration and lung and breast cancer incidences, followed by prostate, bladder, cervical and ovarian cancers, confirming results from other studies. These results could be improved using individual explanatory variables such as environmental, demographic, behavioral, socio-economic, and genetic risk factors.
Little is known about the geographic distribution of common cancers in Saudi Arabia. We explored the spatial incidence patterns of common cancers in Saudi Arabia using spatial autocorrelation analyses, employing the global Moran’s I and Anselin’s local Moran’s I statistics to detect nonrandom incidence patterns. Global ordinary least squares (OLS) regression and local geographically-weighted regression (GWR) were applied to examine the spatial correlation of cancer incidences at the city level. Population-based records of cancers diagnosed between 1998 and 2004 were used. Male lung cancer and female breast cancer exhibited positive statistically significant global Moran’s I index values, indicating a tendency toward clustering. The Anselin’s local Moran’s I analyses revealed small significant clusters of lung cancer, prostate cancer and Hodgkin’s disease among males in the Eastern region and significant clusters of thyroid cancers in females in the Eastern and Riyadh regions. Additionally, both regression methods found significant associations among various cancers. For example, OLS and GWR revealed significant spatial associations among NHL, leukemia and Hodgkin’s disease (r² = 0.49–0.67 using OLS and r² = 0.52–0.68 using GWR) and between breast and prostate cancer (r² = 0.53 OLS and 0.57 GWR) in Saudi Arabian cities. These findings may help to generate etiologic hypotheses of cancer causation and identify spatial anomalies in cancer incidence in Saudi Arabia. Our findings should stimulate further research on the possible causes underlying these clusters and associations.
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