Analysis and Estimates of the Attributable Risk for Environmental and Genetic Risk Factors in Gastric Cancer in a Chinese Population

Abstract

Development of gastric cancer is a multistage, multifactorial process. This study determined the population attributable risk for environmental and genetic risk factors in development of gastric cancer. A 1:1 cancer case-control study was undertaken in Nanjing, Jiangsu Province, China. A conditional-logistic regression model was used to determine environmental and genetic risk factors and calculate attributable risk (AR%) for each environmental and genetic risk factor in gastric cancer. In addition, the summary attributable risk (sAR) for all of the risk factors among 503 cases of gastric cancer patients and controls was determined. The environmental risk factors for gastric cancer in the Nanjing area were family history of tumor, consumption of pickled food, engorgement after hunger, irregular dietary habits, and lack of fruit intake. The genetic risk factors included the following genotypes: CYP2E1 wild, NAT2 M1 mutation, NAT2 slow-acetylators, XRCC1 194 mutation, MTHFR A1298C mutation, and IL-1B mutation. Combining environmental and genetic risk factors, sAR was 76.34%. Data suggest that genetic polymorphisms and environmental risk factors play concurrent roles in the development of gastric cancer. The results of this study indicate preventive strategies to avoid development of gastric cancer based on identified genetic polymorphisms and control of environmental risk factors.

Polymorphisms of XRCC1 and ADPRT Genes and Risk of Noncardia Gastric Cancer in a Chinese Population: a Case-control Study

“…In a recent study, we noted that XRCC1 Arg194Trp was associated with GC risk in Sichuan, a western province in China (Wen et al, 2012). This is consistent with findings in two other studies for overall GC risk in Southwestern and Southeastern China (Shen et al, 2009;Yuan et al, 2010). However, contradictory results have been obtained in three Chinese studies focusing on association of XRCC1 Arg194Trp with cardia GC.…”

“…X-ray repair cross-complementing group 1 (XRCC1) and adenosine diphosphate ribosyl transferase (ADPRT) are two of many proteins involved in the BER pathway. Several genetic polymorphisms have been identified in both ADPRT and XRCC1 genes, of which XRCC1 Arg194Trp (C26304T) (Shen et al, 2000;Ratnasinghe et al, 2004;Liu et al, 2009;Shen et al, 2009;Yan et al, 2009;Yuan et al, 2010) and ADPRT Val762Ala (T2446C) Zhang et al, 2006;Zhang et al, 2009) have been widely studied for association with cardia and/or noncardia GC in the Chinese population, albeit with conflicting results reported.…”

ADPRT Val762Ala and XRCC1 Arg194Trp Polymorphisms and Risk of Gastric Cancer in Sichuan of China

“…The XRCC1 Arg194Trp polymorphism with C to T transition at codon 194 is located at a conserved residue in humans (Lamerdin et al, 1995;Shen et al, 1998), and individuals with Arg/ Arg genotype exhibited highly increased chromosomal breaks (Vodicka et al, 2007). Since Shen et al (2000) suggested that XRCC1 Arg194Trp may be associated with risk of developing gastric cancer in a Chinese population, the association between XRCC1 Arg194Trp and gastric cancer (cardia and/or non-cardia cancers) has been investigated in different ethnicities (Shen et al, 2000;Lee et al, 2002;Ratnasinghe et al, 2004;Duarte et al, 2005;Hong et al, 2009;Liu et al, 2009;Shen et al, 2009;Yan et al, 2009;Palli et al, 2010;Yuan et al, 2010), though the results are conflicting. The ADPRT Val762Ala polymorphism with T to C transition at codon 762 is located in the sixth helix of catalytic domain that causes Val-to-Ala amino acid substitution.…”

Association of NAT2 phenotype with risk of head and neck carcinoma: A meta-analysis

“…However, the carcinogenesis of tobacco is relatively complex and the role of NAT2 described in different studies is not entirely consistent. In the studies concerning the association of NAT2 polymorphisms with the increased risk of gastric cancer, Shen et al (37) indicated that the rapid acetylator was the protective factor for the development of gastric cancer, whereas Ladero et al (38) suggested that it was regarded as a risk factor. However, results in other relevant studies demonstrated that no significant association between NAT2 polymorphisms and gastric cancer was found (37,39,40).…”

“…In the studies concerning the association of NAT2 polymorphisms with the increased risk of gastric cancer, Shen et al (37) indicated that the rapid acetylator was the protective factor for the development of gastric cancer, whereas Ladero et al (38) suggested that it was regarded as a risk factor. However, results in other relevant studies demonstrated that no significant association between NAT2 polymorphisms and gastric cancer was found (37,39,40). This discrepancy has also existed in the studies of other tobacco-associated cancers, including lung cancer (41)(42)(43) and prostate cancer (44)(45)(46).…”