Meta-analysis of studies of the CYP2D6 polymorphism in relation to lung cancer and Parkinson??s disease

Rostami‐Hodjegan, Amin; Ms, Lennard; Hf, Woods; Gt, Tucker

doi:10.1097/00008571-199806000-00005

Cited by 92 publications

(39 citation statements)

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“…PD is known to be associated with polymorphisms of the detoxifying enzyme P450 D6 (CYP2D6) that lead to poor toxin metabolism (26), and this may be the basis for the increased risk of PD in those exposed to certain pesticides (27). Poor metabolism by CYP2D6 is also associated with a decreased risk of lung cancer because there is decreased activation of procarcinogens in cigarette smoke (28). One could hypothesize that poor metabolism of toxins by CYP2D6 might account for an increased risk of toxin-related cancer in the absence of smoking.…”

Section: Discussionmentioning

confidence: 99%

A Prospective Cohort Study of Cancer Incidence Following the Diagnosis of Parkinson's Disease

Driver¹,

Logroscino

Buring

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

144

130

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Background: Prior studies suggest a decreased risk of cancer among patients with Parkinson's disease (PD). Methods: Matched cohort analysis among the 22,071 participants in the Physician's Health Study. A total of 487 incident cases of PD without preceding cancer were identified by self-report. Each PD case was matched by age to a reference participant who was alive and cancer free at the time of PD diagnosis. Both cohorts were followed for incident cancer. We used proportional hazards models to calculate adjusted relative risks (RR) for cancer. Results: A total of 121 cancers were confirmed during a median follow-up of 5.2 years (PD) and 5.9 years (reference). Those with PD developed less cancer (11.0% versus 14.0%), with an adjusted RR of 0.85 [95% confidence interval (95% CI), 0.59-1.22]. Reduced risk was present for smoking-related cancers such as lung (RR, 0.32), colorectal (RR, 0.54), and

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Section: Discussionmentioning

confidence: 99%

A Prospective Cohort Study of Cancer Incidence Following the Diagnosis of Parkinson's Disease

Driver¹,

Logroscino

Buring

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

144

130

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“…Although two meta-analyses 72,74 reported a significant association of the poormetabolizer genotype with PD, the other two did not reveal any significant association. 73,75 In research conducted since the publication of these meta-analyses, no association was found between CYP2D6 polymorphism and the risk of PD. [79][80][81][82][83][84][85][86] CYP2E1 is an ethanol-inducible enzyme apparently involved in the activation of neurotoxicants that increase oxidative stress (OS), a well-known contributory factor in the pathogenesis of PD.…”

Section: Xenobiotic Metabolizing Enzymes Cytochrome P450 System Enzymesmentioning

confidence: 99%

“…70 Several reviews and meta-analysis were performed to determine whether there is an association between cytochrome P450 polymorphisms (CYP2D6, CYP1A1, CYP2C9, CYP2C19, CYP1A2, and CYP2E1) and the risk of PD. [71][72][73][74][75][76] The most studied is the CYP2D6 gene, which encodes for the enzyme debrisoquine 4-hydroxylase that metabolizes a wide range of drugs, including MPTP, and has a number of functional polymorphisms. 77,78 However, the findings were inconclusive.…”

Section: Xenobiotic Metabolizing Enzymes Cytochrome P450 System Enzymesmentioning

confidence: 99%

Polymorphism in candidate genes: implications for the risk and treatment of idiopathic Parkinson's disease

et al. 2004

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Idiopathic Parkinson's disease (IPD) is a progressive neurodegenerative disorder for which no restorative or neuroprotective therapy is available. Interest has recently been directed to association studies on polymorphisms of various genes, mainly those related to dopamine metabolism and transport, and their effect on response to PD, which includes primarily levodopa and dopaminomimetics. Approximately 15-20% of patients with PD do not respond to levodopa, and the majority of those who do respond develop adverse fluctuations in motor response, primarily levodopa-induced dyskinesias. This review summarizes the influence of polymorphisms in various genes on the relative risk of IPD and on levodopa efficacy. It focuses on the importance of well-designed polymorphism studies that include large samples of patients with IPD and tightly matched controls and use identical methodologies. Valid data on such polymorphisms might increase the efficacy of levodopa, decrease its side effects, and reduce the occurrence of levodopa-induced dyskinesias. They might also provide a novel diagnostic tool for PD.

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“…Determined genotypes of some cytochrome P450 enzymes, such as CYP1A1 or CYP2D6, also have been correlated with a decreased risk of lung carcinoma, although meta-analyses have failed to confirm this observation 43,44 or have described only a small protective effect with a nonappreciable relation to individual susceptibility. 45 Two common polymorphisms of the p21WAF1/Cip1 gene have been associated with a potential protective role against ovarian carcinoma. 46 Some genotypes of glutathione S-transferase M1 also have been related to the risk of lung carcinoma and other aerodigestive tract malignancies; although, again, a meta-analysis failed to confirm such results.…”

Section: Studies In Individuals Potentially Protected From Developingmentioning

confidence: 99%

The role of extreme phenotype selection studies in the identification of clinically relevant genotypes in cancer research

Perez-Gracia

Ruiz-Ilundáin

García-Ribas

et al. 2002

Cancer

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The investigation of genetic alterations that may be related to the prognosis of patients with malignant disease has become a frequently used strategy in recent years. Although some conclusions have been reached in certain studies, the complexity and the multifactorial nature of most neoplastic diseases makes it difficult to identify clinically relevant information, and the results of some studies have been of borderline significance or have been conflicting. In contrast, the identification and the study of patients or families with very characteristic phenotypes have yielded outstanding results in the identification of the genetic characteristics underlying such phenotypes. Although, in most cases, the individuals who are selected for these types of studies are characterized by a negative phenotype (i.e., individuals who are at increased risk for developing a specific disease), a few studies have been directed toward individuals with phenotypes that imply an unusually good prognosis (i.e., individuals who present with a decreased risk for developing specific diseases despite an important exposure to well-known risk factors). Therefore, it seems logical to develop this strategy further as a valid methodology for the study of other diseases, such as cancer. The study of individuals with phenotypes that imply an extremely good prognosis, such as long-term survivors of theoretically incurable malignancies or individuals who seem to be protected against a certain neoplastic disorder despite having a markedly increased risk for its development, may unveil genetic alterations that explain such characteristic phenotypes and may provide potentially useful therapeutic targets against these diseases. Cancer 2002;95:1605-10.

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Meta-analysis of studies of the CYP2D6 polymorphism in relation to lung cancer and Parkinson??s disease

Cited by 92 publications

References 0 publications

A Prospective Cohort Study of Cancer Incidence Following the Diagnosis of Parkinson's Disease

A Prospective Cohort Study of Cancer Incidence Following the Diagnosis of Parkinson's Disease

Polymorphism in candidate genes: implications for the risk and treatment of idiopathic Parkinson's disease

The role of extreme phenotype selection studies in the identification of clinically relevant genotypes in cancer research

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