Table 3.

Genetic polymorphisms affecting the genes related to changing the risk of developing esophageal cancer in South Africa and China

Country and polymorphism	OR	Environmental factors	Postulated mechanisms/effect
PLCE1 is involved in the regulation of cell growth, differentiation, apoptosis and angiogenesis
China
rs10882379196 GG => GA GG => AA GG => A/AA	At 95% CI 0.68 0.69 0.75	No association with smoking and alcohol use	SNP is in the promoter region/decreased ESCC risk
rs829232196 GG => GA GG => AA GG => GA/AA	At 95% CI 1.32 1.88 1.42	No association with smoking and alcohol use.	SNP is in the promoter/increased ESCC risk
rs2274223 at 10q2343 AA => AG AA => GG AA => AG/GG	At 95% CI 1.27 1.47 1.30	No association with environmental factors	SNP in exon 26 of PLCE1 gene is associated with increased risk of ESCC. AG and GG genotypes lead to lower PLCE1 mRNA and protein levels
rs11187870197 GG => CG GG => CC GG => CG/CC	At 95% CI 1.1 1.54 1.21	No association with environmental factors	SNP is in the 3′UTR. Associated with increased risk of ESCC
South Africa
Arg548Leu (rs17417407)198	0.75 at 95% CI	No evidence for an association with smoking or alcohol	Associated with a reduced risk of ESCC in the black population
NAT1 and NAT2 are the main Phase II xenobiotic metabolizing enzymes involved in either detoxification or activation of carcinogenic arylamines
China
NAT2 rs1565684199 T > C SNP CC = TC/CC	At 95% CI 1.14 1.77	Alcohol consumption had no effect on ESCC risk	Genotype was associated with an increased risk for ESCC
South Africa
NAT2 341 CC (rs1801280)200 Mixed ancestry black	At 95% CI 0.31 0.55	In the black population group, smokers with this mutation had a higher risk of ESCC	Mutation resulted in decreased acetylation activity and reduced the risk for EC in mixed ancestry group
NAT1 and NAT2 slow/intermediate acetylation phenotype200	0.44 at 95% CI		NAT2 slow/intermediate acetylation/reduced risk of ESCC in mixed ancestry group
CASP8 is an initiator of CASP3, a key regulator of apoptosis, and is important in cancer development and progression
China
rs1035142 G>T201 Heterozygote Homozygote	At 95% CI 1.55 2.34		Associated with an increased risk of ESCC by negatively affecting the cells’ ability to undergo apoptosis
South Africa
(−652 6Ndel:302His)90	2.37 at 95% CI	Associated with ESCC in current smokers, but not in former smokers	Haplotype associated with ESCC in mixed ancestry population
Asp302His (rs1045485)90	1.42 at 95% CI		Suggestive association with increased ESCC risk in mixed ancestry population
p53 can induce cell cycle arrest for DNA repair and/or apoptosis in response to cellular stress such as DNA damage or hypoxia
China
Arg72Pro (rs1042522)6,9,97,202 Pro/Arg vs Pro/Pro Pro vs Arg Pro/Pro vs Arg/Arg + Arg/Pro Pro/Pro vs Arg/Arg Pro/Pro vs Arg/Pro	At 95% CI 1.01 1.83 1.17 1.32 1.35	No significant association with tobacco use	Increased risk of EC in Han Province. Associated with Burkitt’s lymphoma
rs2909430203	1.94 at 95% CI		Commonly observed in ESCC patients in high-risk area of China
rs78378222 A => C203	3.22 at 95% CI
Polymorphisms in exon 4204 C => A, codon 34 G => C, codon 36 G => C, codon 72	At 95% CI 1.03 1.86 0.8	Reactive mutagenic compounds form DNA adducts, which can cause nucleotide changes. TP53 plays an important role responding to DNA damage. Loss of function mutations will increase the threat posed by carcinogens	Strongly associated with EC
Small deletions, insertions and point mutations resulting in frame shifts or amino acid changes in exons 5–8204			Commonly observed in ESCC patients
16 bp duplication in intron 3 resulting in loss of heterozygosity204	14 at 95% CI		Commonly observed in ESCC patients

Abbreviations: EC, esophageal cancer; ESCC, esophageal squamous cell carcinoma; rs, reference SNP cluster ID; SNP, single-nucleotide polymorphism.