Polymorphisms in DNA repair genes and associations with cancer risk.

TLDR

Common polymorphisms in DNA repair genes may alter protein function and reduce DNA repair capacity, potentially leading to genetic instability and carcinogenesis. The study reviews epidemiological evidence linking DNA repair polymorphisms to cancer risk and highlights the need for large, multi‑gene analyses that consider relevant exposures. The authors conducted a MEDLINE search that identified 30 studies on polymorphisms in genes such as OGG1, XRCC1, ERCC1, XPC, XPD, XPF, BRCA2, and XRCC3, covering cancers including glioma, bladder, breast, esophageal, lung, prostate, skin, head and neck, and stomach. The review found that most studies were small, but consistent evidence links the OGG1 S326C variant to higher cancer risk, the XRCC1 R194W variant to lower risk, and the BRCA2 N372H variant to increased breast cancer risk, underscoring the need for larger, well‑designed studies. PubMed Database: http://www.ncbi.nlm.nih.gov/entrez.

Abstract

Common polymorphisms in DNA repair genes may alter protein function and an individual's capacity to repair damaged DNA; deficits in repair capacity may lead to genetic instability and carcinogenesis. To establish our overall understanding of possible in vivo relationships between DNA repair polymorphisms and the development of cancer, we performed a literature review of epidemiological studies that assessed associations between such polymorphisms and risk of cancer. Thirty studies of polymorphisms in OGG1, XRCC1, ERCC1, XPC, XPD, XPF, BRCA2, and XRCC3 were identified in the April 30, 2002 MEDLINE database (National Center for Biotechnology Information. PubMed Database: http://www.ncbi.nlm.nih.gov/entrez). These studies focused on adult glioma, bladder cancer, breast cancer, esophageal cancer, lung cancer, prostate cancer, skin cancer (melanoma and nonmelanoma), squamous cell carcinoma of the head and neck, and stomach cancer. We found that a small proportion of the published studies were large and population-based. Nonetheless, published data were consistent with associations between: (a) the OGG1 S326C variant and increased risk of various types of cancer; (b) the XRCC1 R194W variant and reduced risk of various types of cancer; and (c) the BRCA2 N372H variant and increased risk of breast cancer. Suggestive results were seen for polymorphisms in other genes; however, small sample sizes may have contributed to false-positive or false-negative findings. We conclude that large, well-designed studies of common polymorphisms in DNA repair genes are needed. Such studies may benefit from analysis of multiple genes or polymorphisms and from the consideration of relevant exposures that may influence the likelihood of cancer in the presence of reduced DNA repair capacity.