Association Between XRCC1 ARG399GLN and P53 ARG72PRO Polymorphisms and the Risk of Gastric and Colorectal Cancer in Turkish Population

Abstract

Gastric cancer is one of the most common cancers of the gastrointestinal system, and its overall fi ve-year survival rate is still 15 % to 20 %, as it can mostly be diagnosed at an advanced stage. On the other hand, although colorectal cancer has a rather good prognosis, mortality is one half that of the incidence. As carcinogenesis is believed to involve reactive radicals that cause DNA adduct formation, impaired repair activity, and weakened tumour suppression, it would help to understand the role of the polymorphisms of nucleotide excision repair enzyme XRCC1 and of tumour suppressor gene p53 in gastric and colorectal cancers. Our study included 94 gastric cancer patients, 96 colorectal cancer patients, and 108 cancer-free individuals as control with the aim to see if there was an association between XRCC1 Arg399Gln and p53 Arg72Pro polymorphisms and cancer susceptibility. DNA was extracted from peripheral blood cells and genotypes were determined using the polymerase chain reaction-restriction fragment length polymorphism. Polymorphism p53 Arg72Pro was not associated with either gastric or colorectal carcinoma, while XRCC1 Arg399Gln was not associated with the increased risk of colorectal cancer. However, XRCC1 homozygous Gln allele at codon 399 was associated with 2.54 times higher risk of gastric cancer.

XRCC1 and ADPRT Polymorphisms Associated with Survival in Breast Cancer Cases Treated with Chemotherapy

“…One study conducted in Canada reported XRCC1 Arg399Gln was an independent predictor for progression (Bewick et al, 2009), and another study showed a nonsignificant decreased risk of survival for breast cancer (Rodrigues et al, 2011). Similar results were found for the survival of non-small-cell lung cancer, colorectal cancer, gastric cancer and ovarian cancer (Khrunin et al, 2010;Engin et al, 2011;Tahara et al, 2011;Liao et al, 2012).…”

“…The gene polymorphism in codon 399 may be related to DNA repair, and likely has an effect on protein function (Savas et al, 2004). Several studies have found an association of XRCC1-399 with the risk of various cancers, such as breast cancer, colorectal cancer, lung cancer, thyroid carcinoma, gastric cancer and breast cancer (Engin et al, 2011;Fard-Esfahani et al, 2011;Xu et al, 2011;Raabe et al, 2012;Zhao et al, 2012). Previous study showed an improved survival rate for breast cancer patients with XRCC1-399 Gln/Gln receiving chemotherapy (Bewick et al, 2009;Rodrigues et al, 2011).…”

The Codon 399 Arg/Gln XRCC1 Polymorphism is Associated with Lung Cancer in Indians

“…A recent study by Karkucak et al (2012) reported no association of XRCC1 gene Arg399Gln polymorphism in lung cancer risk. But variations between individuals, lacking DNA repair capacity in humans may be prone to risk of various cancers as reported by Hu et al (2011) in Glioma, gastric cancer by Engin et al (2011) and Kumar et al (2012) reported risk in Head and neck cancers.…”

Investigating the association between XRCC1 gene polymorphisms and susceptibility to gastric cancer

“…However, Hsu et al (2015) found no significant association between XRCC1 gene polymorphisms and skin cancer risk, although in a case-control study, Zhu et al (2015) demonstrated that individuals carrying the Arg194Trp variation in this gene are more susceptible to prostate cancer. Several investigators have scrutinized the association between XRCC1 gene polymorphisms and gastric cancer risk, but their results have been inconsistent (Yan et al, 2009;Engin et al, 2011;Yuan et al, 2011;Karahalil et al, 2012;Pan et al, 2012;Wen et al, 2012). In Turkish populations, Engin et al (2011) and Karahalil et al (2012) found a statistically significant association between the XRCC1 Arg399Gln gene polymorphism and gastric cancer risk in Turkish populations.…”

“…Several investigators have scrutinized the association between XRCC1 gene polymorphisms and gastric cancer risk, but their results have been inconsistent (Yan et al, 2009;Engin et al, 2011;Yuan et al, 2011;Karahalil et al, 2012;Pan et al, 2012;Wen et al, 2012). In Turkish populations, Engin et al (2011) and Karahalil et al (2012) found a statistically significant association between the XRCC1 Arg399Gln gene polymorphism and gastric cancer risk in Turkish populations. Wen et al (2012), Pan et al (2012), andYuan et al (2011) revealed a significant relationship between the Arg194Trp variant and susceptibility to this disease among Chinese individuals, while Yan et al (2009) reported that Arg399Gln and Arg194Trp sequence alterations have no effect, but the Arg280His polymorphism significantly increases gastric cancer risk.…”