GPX Pro198Leu and OGG1 Ser326Cys polymorphisms and risk of development of colorectal adenomas and colorectal cancer

Abstract

Little is known about genetic risk factors for colorectal cancer. We assessed the association between polymorphisms in two genes involved in DNA repair of oxidative stress, GPX and OGG1, and risk of colorectal carcinoma or adenomas. We studied 166 cases with adenocarcinoma, 974 with adenomas and 397 controls recruited from the Norwegian cohort NORCCAP. No associations were found between the polymorphism GPX Pro 198Leu and risk of colorectal adenomas or carcinomas. Carriers of the variant allele OGG1 Ser 326 Cys polymorphism had a lowered risk of colorectal cancer, OR = 0.56 (95% confidence interval 0.33-0.95), while no association were found with risk of adenomas. This indicates that a low repair capacity of oxidative DNA damage may not be a risk factor for development of colorectal adenomas or carcinoma.

The hOGG1 Ser326Cys Polymorphism Is Not Associated with Colorectal Cancer Risk

“…They concluded that the hOGG1 S326C polymorphism may be protective against colorectal cancer development but not carcinogenesis. 15 These findings are not consistent with those of the present study involving over 400 carcinoma cases in the Korean population.…”

“…Of the two similar previous studies, Kim et al 14 also found no association between the Ser326Cys polymorphism and colorectal cancer risk. In contrast to these findings, a study of over 1,000 Norwegians by Hansen et al 15 concluded the hOGG1 Ser326Cys variant was indeed associated with colon cancer. They found that carriers of the rare Cys allele had a lower risk of colorectal cancer, particularly of adenocarcinoma (166 patients), but not a lower risk of adenoma.…”

“…[8][9][10][11][12][13] The issue of whether the hOGG1 Ser326Cys polymorphism is associated with colorectal cancer remains controversial. 14,15 In the present study, we investigated whether the hOGG1 Ser326Cys polymorphism was associated with colorectal cancer risk by genotyping over 1,000 colorectal cancer patients and normal controls from the Korean population. In addition, we investigated whether the Ser326Cys polymorphism and colorectal cancer risk might be modulated by clinico-pathological characteristics such as tumor location, tumor-node-metastasis (TNM) stage or microsatellite instability (MSI) status.…”

“…7,11,18 Consistent with those reports, the present study found a higher proportion of Cys/Cys genotype frequencies in this Korean population (33.0% in controls, 29.2% in cases) compared to that reported for Western populations, in particular Norwegians (12.1% in controls, 7.9% in cases). 15 Thus, it appears the hOGG1 S326C polymorphism may be differently distributed among different ethnic groups. These findings indicate the need for studies examining whether the Ser326Cys polymorphism is associated with colorectal cancer in larger Asian populations such as the Chinese or Japanese.…”

Base Excision Repair Pathways

“…The Ser326Cys homozygous populations were at increased risk for colorectal cancer, only when other incriminating factors (increased meat intake, cigarette smoking) were co-present (Kim et al, 2003). Other studies however have not found a correlation between this polymorphism and colorectal adenomas or carcinomas (Hansen et al, 2005). On the contrary, mutations in the MYH gene (see also subchapter 4) have been proven without doubt to be able to cause an autosomal recessive form of familial adenomatous polyposis (Lindor, 2009).…”