Multi-institutional prostate cancer study of genetic susceptibility in populations of African descent

Abstract

Prostate cancer disparities have been reported in men of African descent who show the highest incidence, mortality, compared with other ethnic groups. Few studies have explored the genetic and environmental factors for prostate cancer in men of African ancestry. The glutathione-S-transferases family conjugates carcinogens before their excretion and is expressed in prostate tissue. This study addressed the role of GSTM1 and GSTT1 deletions on prostate cancer risk in populations of African descent. This multi-institutional case-control study gathered data from the Genetic Susceptibility to Environmental Carcinogens (GSEC) database, the African-Caribbean Cancer Consortium (AC3) and Men of African Descent and Carcinoma of the Prostate Consortium (MADCaP). The analysis included 10 studies (1715 cases and 2363 controls), five in African-Americans, three in African-Caribbean and two in African men. Both the GSTM1 and the GSTT1 deletions showed significant inverse associations with prostate cancer [odds ratio (OR): 0.90, 95% confidence interval (CI) 0.83-0.97 and OR 0.88, 95% CI: 0.82-0.96, respectively]. The association was restricted to Caribbean and African populations. A significant positive association was observed between GSTM1 deletion and prostate cancer in smokers in African-American studies (OR: 1.28, 95% CI: 1.01-1.56), whereas a reduced risk was observed in never-smokers (OR: 0.66, 95% CI: 0.46-0.95). The risk of prostate cancer increased across quartiles of pack-years among subjects carrying the deletion of GSTM1 but not among subjects carrying a functional GSTM1. Gene-environment interaction between smoking and GSTM1 may be involved in the etiology of prostate cancer in populations of African descent.

Copy Number Variation of GSTT1 and GSTM1 and the Risk of Prostate Cancer in a Caribbean Population of African Descent

“…This finding is consistent with a previous observation of an association between homozygous GSTT1 deletion and a lower risk of prostate cancer in Caribbean men who had never smoked [14]. Such observations contrast with those reported for African-American men, in whom homozygous GSTM1 deletion was associated with an increase in the risk of prostate cancer among smokers, whereas homozygous GSTT1 deletion was not [14]. The observed differences in such associations between Caribbean and African-American men suggest possible differences in various factors between these populations, including lifetime exposure to other carcinogens that saturate the GST system, different levels of tobacco consumption and possible differences in the composition of cigarettes between countries.…”

Interaction between GSTT1 and GSTP1 allele variants as a risk modulating-factor for autism spectrum disorders

“…Several of the GST family subgroup genes, including GST mu 1 ( GSTM1 ), GST pi 1 ( GSTP1 ), and GST theta 1 ( GSTT1 ), are highly polymorphic (Loktionov et al, 2001). Sequence variation in these genes has also been associated with an increased or decreased risk for several cancers and chronic diseases, including colorectal cancer (Loktionov et al, 2001), esophageal cancer (Sharma et al, 2013), renal cell carcinoma (Cheng, You, & Zhou, 2012; Yang et al, 2013), acute leukemia (Ye & Song, 2005), prostate cancer (Harries, Stubbins, Forman, Howard, & Wolf, 1997; Kote-Jarai et al, 2001; Liu, Liu, Ran, Shang, & Li, 2013; Safarinejad, Shafiei, & Safarinejad, 2011; Taioli et al, 2011; Wei et al, 2013), type-2 diabetes mellitus (Dadbinpour, Sheikhha, Darbouy, & Afkhami-Ardekani, 2013; Ramprasath et al, 2011), asthma (Tamer et al, 2004), and neurodevelopmental disorders such as ASD (Buyske et al, 2006). The variants in GSTM1 and GSTT1 examined here are insertion-deletion polymorphisms, and the homozygous deletions or null genotypes indicate that activities or functionality of these genes are reduced or interrupted completely (Ye, Song, Higgins, Pharoah, & Danesh, 2006).…”

Quantitative assessment of the association between glutathione S-transferase M1 polymorphism and the risk of developing nasopharyngeal cancer

“…GSTM1, one of the main subtypes of GSTs, participates in the protection of the host against cancer (4). The GSTM1 gene displays several polymorphisms, among which, the null variant is the most common one, and it has been widely investigated as a risk biomarker for various types of cancer (7,8). The GSTM1 null variant may result in the absence of enzymatic activity, and individuals who carry the null variant are thought to be at increased risk of developing cancer, since the polymorphic deletions of GSTs may affect their ability to detoxify electrophilic carcinogens, which may lead to an increase in the host's susceptibility to environmental toxins and carcinogens (6,33).…”

“…The GSTM1 gene is located on the short arm of chromosome 1 (1p13.3), and displays several polymorphisms (6). The most common polymorphism in the GSTM1 gene is a null variant, which has been widely investigated as a risk biomarker for various types of cancer (7,8). The GSTM1 null variant may lead to the absence of enzymatic activity, and individuals who carry this variant are thought to be at increased risk of developing cancer (6).…”