DNA Repair Single-Nucleotide Polymorphisms in Colorectal Cancer and their Role as Modifiers of the Effect of Cigarette Smoking and Alcohol in the Singapore Chinese Health Study

Abstract

Recently, we reported that among Singapore Chinese, cigarette smoking and alcohol drinking were independent risk factors for colorectal cancer. Both tobacco smoking and alcohol use are plausible colorectal cancer risk factors, partly due to their ability to induce mutations in the colorectal lumen. . We conducted this study within the Singapore Chinese Health Study, a population-based cohort of 63,257 middle-aged and older Singapore Chinese men and women enrolled between 1993 and 1998. Our study included 1,176 controls and 310 cases (180 colon and 130 rectum cancer). We observed a positive association between the PARP codon 940 Lys/Arg and Arg/Arg genotypes and colorectal cancer risk [odds ratio (OR), 1.8; 95% confidence interval (95% CI), 1.1-3.1], and an inverse association between the MGMT codon 84 Leu/Phe or Phe/Phe genotypes and colon cancer risk (OR, 0.6; 95% CI, 0.3-0.9), but not rectal cancer (test of heterogeneity by tumor site, P = 0.027). We observed evidence that XRCC1 may modify the effects of smoking (interaction P = 0.012). The effect of smoking among carriers of the Arg 194 -Gln 399 haplotype was OR = 0.7 (95% CI, 0.4-1.1), whereas, among carriers of the Trp 194 -Arg 399 haplotype, it was OR = 1.6 (95% CI, 1.1-2.5). We also observed a nonstatistically significant modification of XRCC1 on the effects of alcohol (P = 0.245). Whereas alcohol had no effect among carriers of the codon 194 Arg/Arg (OR, 1.0; 95% CI, 0.6-1.7) or Arg/Trp genotypes (OR, 1.1; 95% CI, 0.6-1.9), there was a positive association among carriers of the Trp/Trp genotype (OR, 2.8; 95% CI, 1.0-8.1). Our results support a role for reactive oxygen species as relevant genotoxins that may account for the effects of both smoking and alcohol on colorectal cancer risk. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2363 -72)

Novel Mutations of the PARP-1 Gene Associated with Colorectal Cancer in the Saudi Population

“…However, previous studies have reviled that Val762Ala SNP was associated with increased overall cancer risk only in Chinese population and was associated with decreased risk among Caucasians (Yu et al, 2012). In our study we found no significant association between PARP-1 Val762Ala SNP and risk of CRC in Saudi population, the same result was also found in Singapore Chinese population (Stern et al, 2007). Although PARP-1 Val762Ala SNP has been suggested to contribute in cancer development (Wang et al, 2007), to our knowledge, no previous studies have investigated the association between PARP-1 Val762Ala SNP and risk of CRC in Middle Eastern countries, particularly in Saudi Arabia.…”

“…As we mentioned above this polymorphism was associated with increased risk of CRC only in Singapore Chinese population (Stern et al, 2007) and that was the only study done to associate between the PARP-1 Lys940Arg SNP and CRC susceptibility; therefore, it is unknown whether this SNP is or is not associated with CRC risk in other populations. Instead of Lys940Arg polymorphism, we found another alteration, with a heterozygous A/C allele, in 16% of the CRC patients and 12% of the control subjects.…”

“…Previous study suggested that Lys940Arg SNP may affect the response to chemotherapeutic agents in particular to DNA-damaging agents in patients with lung cancer (Shiraishi et al, 2010). However, this SNP was associated with increased risk of gastric cancer in Chinese population (He et al, 2012) and CRC in Singapore Chinese (Stern et al, 2007). Also it can contribute in the development of human germ cell tumors (Shiokawa et al, 2005).…”

Association Between Six Genetic Polymorphisms and Colorectal Cancer: A Meta-Analysis

“…Associations between six single-nucleotide polymorphisms (SNPs) of the earlier-mentioned five genes and CRC have been reported in different ethnic groups (Smith et al, 2001;Landi et al, 2003Landi et al, , 2005Krzesniak et al, 2004;Jiang et al, 2005;McGreavey et al, 2005;Murtaugh et al, 2005;Slattery et al, 2005Slattery et al, , 2006Berndt et al, 2006;Huang et al, 2006;Koh et al, 2006;Kuriki et al, 2006;Matsuo et al, 2006;Moreno et al, 2006;Theodoropoulos et al, 2006;Tranah et al, 2006;Hansen et al, 2007;Kang et al, 2007;Stern et al, 2007;Vogel et al, 2007;Yin et al, 2007;Kury et al, 2008;Funke et al, 2009;Khatami et al, 2009;Tsilidis et al, 2009;Yang et al, 2009;Engin et al, 2010;Meplan et al, 2010;Loh et al, 2011;Wu et al, 2011;Crous-Bou et al, 2012;Gil et al, 2012). These six variants comprised rs12917 and rs2308321 of MGMT, rs1229984 of ADH1B, rs4880 of SOD2, rs2228001 of XPC, and rs1801282 of PPARG.…”

Polymorphisms in XRCC1 Gene, Alcohol drinking, and Risk of Colorectal Cancer: a Case-control Study in Jiangsu Province of China

“…These coding polymorphisms, resulting in amino acid substitutions, were detected at codons 194 (Arg-Trp, rs1799782), 399 (Arg-Gln, rs25487) and 280 (Arg-His). Many authors have analysed relationship between the XRCC1 polymorphisms and the risk of several cancers, including colorectal cancer, however study findings have been inconsistent (Abdel-Rahman et al, 2000;Yeh et al, 2005;Stern et al, 2007;Jin et al, 2007Jin et al, , 2008Improta et al, 2008;Curtin et al, 2009;Wang et Canbay et al, 2011;Gsur et al, 2011;Reeves et al, 2012;Jelonek et al, 2012;Karahalil et al, 2012). Hong et al (2005) in South Korean and Yin et al (2012) in Japanese observed an increased risk of colorectal cancer associated with the XRCC1 Arg399Gln polymorphism and high alcohol intake.…”