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Case-control analysis of nucleotide excision repair pathway and the risk of renal cell carcinoma.

ABSTRACT: In this population-based case-control study with 325 Caucasian renal cell carcinoma (RCC) patients and 335 controls matched to cases by age, gender and county of residence, we evaluated the associations between 13 potential functional polymorphisms in nine major nucleotide excision repair (NER) genes and RCC risk. In individual single nucleotide polymorphism analysis, after adjustment for multiple comparisons, a significantly decreased RCC risk was observed for the heterozygous genotype of XPD Asp312Asn [odds ratio (OR) = 0.62; 95% confidence interval (CI): 0.43-0.90] and for the heterozygous and homozygous variant genotypes combined in a dominant model (OR = 0.64; 95% CI: 0.46-0.89). The heterozygous AG genotype of XPA 5'untranslated region was at 1.78-fold increased risk (95% CI: 1.18-2.69) and the risk reached 2.43-fold (95% CI: 1.57-3.75) for the homozygous variant GG genotype; the risk was significant both in the dominant model and in the recessive model. In joint analysis, compared with individuals with fewer than five adverse alleles, individuals with five (OR = 1.17; 95% CI: 0.71-1.93), six (OR = 1.66; 95% CI: 1.03-2.67), seven or more (OR = 1.85; 95% CI: 1.16-2.95) exhibited a progressively increased risk of RCC (P for trend = 0.004). Further, there were significant interactions between NER pathway genes and sex, hypertension and obesity (all P for interaction <0.05). Our results strongly support that common sequence variants of the NER pathway genes predispose susceptible individuals to increased risk of RCC and that the association may be modified by gender, history of hypertension and obesity. These results need to be replicated in larger studies.

SUBMITTER: Lin J

PROVIDER: S-EPMC2722861 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature

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Case-control analysis of nucleotide excision repair pathway and the risk of renal cell carcinoma.

Lin Jie J Pu Xia X Wang Wei W Matin Surena S Tannir Nizar M NM Wood Christopher G CG Wu Xifeng X

Carcinogenesis 20080818 11

In this population-based case-control study with 325 Caucasian renal cell carcinoma (RCC) patients and 335 controls matched to cases by age, gender and county of residence, we evaluated the associations between 13 potential functional polymorphisms in nine major nucleotide excision repair (NER) genes and RCC risk. In individual single nucleotide polymorphism analysis, after adjustment for multiple comparisons, a significantly decreased RCC risk was observed for the heterozygous genotype of XPD A ...[more]

PMID: 18711149

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Project description:The role of occupation in the etiology of renal cell carcinoma (RCC) is unclear. Here, we investigated associations between employment in specific occupations and industries and RCC, and its most common histologic subtype, clear cell RCC (ccRCC).Between 2002 and 2007, a population-based case-control study of Caucasians and African Americans (1,217 cases; 1,235 controls) was conducted within the Detroit and Chicago metropolitan areas to investigate risk factors for RCC. As part of this study, occupational histories were ascertained through in-person interviews. We computed odds ratios (ORs) and 95% confidence intervals (CIs) relating occupation and industry to RCC risk using adjusted unconditional logistic regression models.Employment in the agricultural crop production industry for five years or more was associated with RCC (OR?=?3.3 [95% CI?=?1.0-11.5]) and ccRCC in particular (OR?=?6.3 [95% CI?=?1.7-23.3], P for trend with duration of employment?=?0.0050). Similarly, RCC risk was elevated for employment of five years or longer in non-managerial agricultural and related occupations (ORRCC?=?2.1 [95% CI?=?1.0-4.5]; ORccRCC?=?3.1 [95% CI?=?1.4-6.8]). Employment in the dry-cleaning industry was also associated with elevated risk (ORRCC?=?2.0 [95% CI?=?0.9-4.4], P for trend?=?0.093; ORccRCC?=?3.0 [95% CI?=?1.2-7.4], P for trend?=?0.031). Suggestive elevated associations were observed for police/public safety workers, health care workers and technicians, and employment in the electronics, auto repair, and cleaning/janitorial services industries; protective associations were suggested for many white-collar jobs including computer science and administrative occupations as well employment in the business, legislative, and education industries.Our findings provide support for an elevated risk of RCC in the agricultural and dry-cleaning industries and suggest that these associations may be stronger for the ccRCC subtype. Additional studies are needed to confirm these findings.

Dataset Information

Case-control analysis of nucleotide excision repair pathway and the risk of renal cell carcinoma.

Publications

Case-control analysis of nucleotide excision repair pathway and the risk of renal cell carcinoma.

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