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M R Spitz

Publications and source records attributed to M R Spitz.

At least 19 recordsLinked to original sources
PubMed2000

Epidemiologic determinants of clinically relevant prostate cancer.

While tumor volume and Gleason scores are the best available prognostic indicators for prostate cancer, contemporary predictive methods are unable to identify which men with Gleason scores of 7 have clinically insignificant tumors that will not progress and which men will develop highly aggressive prostate cancer. Our objective was to evaluate potential environmental determinants of significant prostate cancer. Subjects were patients identified from a university-based hospital and tertiary cancer center who had undergone radical prostatectomy for prostate cancer. Cases were 103 patients whose tumor volumes were </=0.5 ml. The comparison group was comprised of 225 men with larger-volume disease or with histologic evidence of extracapsular extension but without lymph node involvement. The matching criteria were ethnicity, age at diagnosis (+/-5 years), and date of diagnosis (+/-1 year). Epidemiologic data, current weight, and height were obtained. The comparison group was significantly more likely than cases to be current smokers (7.6% vs. 3.9%) and to report more pack-years smoked (30.1 vs. 23.0 years, p = 0.06). Cases tended to weigh less (85.2 vs. 87.1 kg, p = 0.1) and have lower body mass indices (26.8 vs. 27.6, p = 0.07). A similar trend was evident for weight at age 40 (79 vs. 81 kg). Cases reported a mean weight gain of 4.9 kg compared with 6. 6 kg in the comparison subjects (p = 0.05) between the ages of 25 and 40. There was no significant difference in weight gain from age 40 to current age. Cases were more likely to report having prostate cancer screening (90% vs. 80%, p = 0.02). Cases with Gleason scores </=7 (3 + 4, with 3 being the dominant grade) were younger at diagnosis than those with scores of 7 (4 + 3, with 4 being the dominant grade), were more likely (93%) to have had prostate screening, were less likely to be current smokers (4%), reported the fewest pack-years smoked (21.5 vs. 28.6 years for high-score cases and 30.1 for comparison subjects), and had the lowest average weight gain from ages 25 to 40 (4.62 vs. 6.31 kg for high-score cases). Weight gain in early adulthood and smoking thus appear to be important predictors of virulent prostate cancer. Our data also suggest that prior screening is associated with diagnosis of lower-volume and lower-score disease.

Age Factors↗
PubMed2000

Joint effect of insulin-like growth factors and mutagen sensitivity in lung cancer risk.

BACKGROUND: We hypothesize that accumulation of genetic damage is dependent on an individual's intrinsic carcinogen sensitivity and on various humoral factors (e.g., insulin-like growth factors [IGFs]) that enhance proliferation, resistance to apoptotic cell death, and clonal outgrowth of genetically damaged cells. We tested this hypothesis by determining whether proliferation potential and genetic instability are associated with the risk of lung cancer. METHODS: In a study of 183 lung cancer patients and 227 matched control subjects, we examined the joint effects of latent genetic instability (measured as mutagen sensitivity) and elevated proliferation potential (assessed by measuring IGFs) in lung cancer risk. Levels of IGF-I, IGF-II, and IGF-binding protein-3 (IGFBP-3) in plasma were measured by use of immunoassay kits. Mutagen sensitivity was assessed by quantitating bleomycin- and benzo[a]pyrene diol epoxide (BPDE)-induced chromatid breaks in peripheral blood lymphocyte cultures. RESULTS: Although not statistically significant, the mean levels of IGF-I and the molar ratio of IGF-I/IGFBP-3 were higher in patients with advanced or poorly differentiated disease than in patients with early or well-differentiated disease. Variation in IGFs was not associated with any specific histologic type or tumor stage. High levels of IGF-I and enhanced mutagen sensitivity were individually associated with increased risk of lung cancer: odds ratio (OR) of 2.13 (95% confidence interval [CI] = 1.20-3.78) for IGF-I, 2.50 (95% CI = 1. 49-4.20) for bleomycin sensitivity, and 2.95 (95% CI = 1.72-5.06) for BPDE sensitivity. The OR was statistically significantly elevated to 8.88 for both higher IGF-I and bleomycin sensitivity (95% CI = 3.67-21.50) and to 13.53 for higher IGF-I and BPDE sensitivity combined (95% CI = 4.48-40.89). With all three risk factors considered together, the OR was 17.09 (95% CI = 4.16-70.27). High levels of IGFBP-3 alone were associated with reduced lung cancer risk: OR = 0.59 (95% CI = 0.33-1.05). CONCLUSIONS: Our data suggest that individuals with genetic instability and higher proliferation potential are at enhanced risk for lung cancer.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed2000

Adenocarcinoma of the lung in young patients: the M. D. Anderson experience.

BACKGROUND: Surveillance, Epidemiology, and End Results (SEER) data for the years 1973-1992 documented that patients age < 50 years presented with more advanced disease. Because of the increase in the incidence rate of lung adenocarcinoma in the past few decades and the presentation of more advanced disease in young patients, this study was performed to determine whether differences in survival exist between younger and older patients with this disease. METHODS: The authors reviewed the experience of the University of Texas M. D. Anderson Cancer Center between 1985-1994, encompassing 157 patients age < 40 years of 4097 patients registered with adenocarcinoma of the lung. For comparison, 157 patients age > 50 years with lung adenocarcinoma were selected; these patients were matched for gender, stage of disease at presentation, and definitive therapy modality to assess survival differences more accurately. Data regarding exposure to second-hand smoke were not collected secondary to lack of documentation in the charts reviewed. RESULTS: There were no significant differences between the 2 groups with regard to the overall survival rate (P = 0.34) or time to progression (P = 0.43). Smoking status (current vs. former vs. never-smoker) was not found to be predictive of survival in either the younger group (P = 0.51) or the older group (P = 0.92). CONCLUSIONS: The data from the current study indicate that overall survival and disease free survival rates were not significantly different in these two groups. Thus, the younger patient population should be treated similarly to the older patient population. However, a surprisingly high percentage of younger patients were female (45%) and had never smoked (27%), suggesting that risk factors other than active smoking may be involved in lung carcinogenesis in these patients.

Adenocarcinoma↗
PubMed2000

Analysis of aromatic DNA adducts and 7,8-dihydro-8-oxo- 2'-deoxyguanosine in lymphocyte DNA from a case-control study of lung cancer involving minority populations.

The purpose of this study was to examine the level of smoking-related aromatic DNA adducts and oxidative DNA damage in current smokers from a lung cancer case-control study in African Americans and Mexican Americans. In addition, mutagen sensitivity (bleomycin-induced chromatid breaks), a marker of genetic susceptibility, was assessed in these patients and correlated with the level of DNA damage. Lymphocyte DNA from cases and age-, sex-, and ethnicity-matched controls was analyzed for aromatic DNA adducts (43 cases and 47 controls) and the level of 7, 8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dG) was determined in 46 cases and 48 controls using (32)P-postlabeling. Overall, lung cancer cases had significantly (P < 0.05) higher levels of aromatic DNA adducts and 8-oxo-dG (mean+/-SEM; 6.03+/-1.16/10(8) nucleotides and 5.82+/-0.77/10(5) nucleotides, respectively) compared to the controls (2.80+/-0.36/10(8) nucleotides and 3.65+/-0.56/10(5) nucleotides, respectively). The case-control differences for these two biomarkers were especially evident in current smokers. Both male and female lung cancer cases had higher levels of aromatic DNA adducts compared to the corresponding controls but only in men was the difference statistically significant (P=0.002). Cases who started smoking at earliest age had highest levels of aromatic DNA adducts and 8-oxo-dG. The level of aromatic DNA adducts in lung cancer cases, but not controls, was positively correlated with bleomycin-induced chromatid breaks (P=0.011). In contrast, the level of 8-oxo-dG was not correlated with mutagen sensitivity in either cases or controls or with the level of aromatic DNA adducts. The data suggest that levels of both aromatic DNA adducts and 8-oxo-dG may be useful in predicting risk of lung cancer in these minority populations. The correlation between aromatic DNA adducts and mutagen sensitivity in lung cancer cases and the trend for higher levels of DNA damage in cancer cases who started smoking earliest are particularly interesting and merit further study.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2000

Gender difference in smoking effect on chromosome sensitivity to gamma radiation in a healthy population.

In the general population, there is variation in radiosensitivity associated with cancer risk. However, data on the role of epigenetic factors in the variation of radiosensitivity are scarce. Thus we investigated the effects of smoking and age on the radiosensitivity of human lymphocytes by measuring the frequency of chromosome aberrations after in vitro exposure to gamma rays in peripheral lymphocytes from 441 healthy subjects (18-95 years old). We analyzed the frequency of both spontaneous (baseline) and in vitro gamma-ray-induced (1.5 Gy) chromatid breaks in 50 well-spread metaphases per subject. The overall mean frequencies of spontaneous and induced breaks were 0.02 and 0.45 per cell, respectively. The mean frequency of induced breaks was significantly higher in men than in women (P = 0.03) but did not differ by age or ethnicity. Donors who had ever smoked showed a small but significantly increased frequency of induced breaks (mean = 0.47) compared to nonsmokers (mean = 0.41; P = 0.005). Further stratification and multivariate analyses revealed that the smoking effect was more pronounced in men than in women. These findings support a smoking effect on radiosensitivity in a healthy population, particularly in men. Therefore, when evaluating the association between radiosensitivity and susceptibility to smoking-related cancers, the effect of smoking should be taken into account.

Adult↗
PubMed2000

Genetic variants of myeloperoxidase and lung cancer risk.

The cytochrome P450 family of enzymes is responsible for many of the initial metabolic conversions of procarcinogenic compounds in tobacco smoke to reactive metabolites. However, other enzyme-based systems such as myeloperoxidase (MPO) may also be involved in this metabolic process. MPO is a phase I metabolic enzyme that has a polymorphic region upstream of the gene that appears to reduce transcriptional activity. The polymorphic G-->A nucleotide base shift negates the binding region for the general transcription factor SP1. Thus, individuals with the variant allele may be provided with a protective effect due to decreased metabolic conversion of carcinogenic compounds in tobacco smoke. This study has investigated the hypothesis that individuals with the variant allele may be at a reduced risk for lung cancer. Our results demonstrate that the protective effects of the MPO variant allele reduced overall lung cancer risk in Caucasians by 48% (OR = 0.52, 95% CI 0.30-0.90, P = 0.02). There was a 72% protective effect (OR = 0.28, 95% CI 0.12-0.61, P < 0.05) evident in men but not in women. Additionally, in younger individuals (<61 years) there was a statistically significant 72% reduction in risk (OR = 0.28, 95% CI 0. 11-0.69, P < 0.05) but not in older individuals. A protective effect was observed for current smokers (OR = 0.24, 95% CI 0.10-0.58, P < 0. 05) but not in former smokers and those who had never smoked. These data demonstrate that there is a reduction in lung cancer risk associated with a variant allele of MPO that is evident in men, younger individuals and current smokers.

Base Sequence↗
PubMed1999

Limiting the location of a putative human prostate cancer tumor suppressor gene at chromosome 13q14.3.

We studied loss of heterozygosity (LOH) on human chromosome 13q in prostate cancer specimens to determine the location of a putative tumor suppressor gene (TSG) and to correlate these losses with the clinicopathological stage of the disease. Overall 13 (21%) of 61 specimens analysed had an allele loss on the long arm of chromosome 13. The most frequent (37%) LOH among the informative cases with allele losses was detected at the D13S284 locus on chromosome 13q14. 3. A portion of the DNA segment that spans this locus and is flanked by the microsatellite loci D13S153 and D13S163 was lost in 85% of the specimens with allele losses and was designated as a LOH cluster region (LCR). The LCR spans more than 6 Mbp of DNA. The results suggest that a TSG relevant for the development of prostate cancer is located telomeric to the RB locus. There was a significant correlation (P=0.0024) between chromosome 13q LOH and advanced metastatic disease, suggesting that loss of 13q14.3 region is associated with prostate cancer progression. However, further research must be conducted to establish the identity and function of this putative TSG.

Chromosome Mapping↗
PubMed1999

Family history of cancer, mutagen sensitivity, and increased risk of head and neck cancer.

To evaluate individual cancer susceptibility, 170 previously untreated patients with pathologically-confirmed squamous cell carcinoma of the oral cavity, pharynx, and larynx, and 175 age- and sex-matched health controls were investigated for the occurrence of cancer in first-degree relatives along with other established risk factors for head and neck cancer. More than 54% of these subjects were assayed for mutagen sensitivity by quantifying in-vitro bleomycin-induced chromosomal breaks within peripheral blood lymphocytes. After adjusting for age, gender, education, family income, tobacco and alcohol consumption, the odds ratio associated with three or more first-degree relatives with cancer at any site was 3.79 (95% CI 0.9-15.9) with a linearly-increased trend in risk (P = 0.040). Significantly elevated risk was found to be associated with a history of cancer within siblings (OR = 2.61, 1.2-5.6, P = 0.014). Patients with a family cancer history and mutagen sensitivity were at greatest risk (OR = 7.88, 2.5-25.3, P = 0.005), indicating an additive interactive effect. The findings suggested that genetic familial influence is important in the causation of head and neck cancer.

Aged↗
PubMed1999

Glutathione-S-transferase polymorphisms and risk of squamous-cell carcinoma of the head and neck.

Differences in genetic susceptibility to tobacco-induced carcinogenesis appear to modulate an individual's risk of squamous-cell carcinoma of the head and neck (SCCHN). Risk for SCCHN may be associated with the null alleles of the carcinogen-metabolizing genes glutathione-S-transferase (GST) T1 and GSTM1. In this study, we evaluated the association between GSTM1 and GSTT1 null genotypes and risk of SCCHN in a matched case-control study of 162 patients with SCCHN and 315 healthy controls. Our results showed that 53.1% of cases and 42.9% of controls were null for GSTM1, whereas 32.7% of cases and 17.5% of controls were null for GSTT1 (p < 0.05 and p < 0.001, respectively). Furthermore, 19.8% of cases but only 7.9% of controls were null for both genes (p < 0.001). Multivariate analysis using logistic regression models, including age, sex, ethnicity, smoking status, alcohol status and GST genotypes, showed that both of these genotypes remained independent risk factors for disease [adjusted odds ratios (ORs) = 1.50 and 2.27, respectively; 95% confidence intervals (CIs) = 1.01-2.23 and 1.43-3.60, respectively). When the genotypes were divided into neither null, either null or both null, there was a dose-response relationship (adjusted OR = 1.50, 95% CI = 0.98-2.30) for the either-null group and (adjusted OR = 3.64, 95% CI = 1.94-6.84) for the both-null group (p < 0.001, trend test). Our findings suggest that the GSTM1 and GSTT1 null genotypes are independent risk factors for SCCHN and markers for genetic susceptibility to tobacco-induced carcinogenesis.

Adult↗
PubMed1999

Plasma levels of insulin-like growth factor-I and lung cancer risk: a case-control analysis.

BACKGROUND: Insulin-like growth factors (IGFs), in particular IGF-I and IGF-II, strongly stimulate the proliferation of a variety of cancer cells, including those from lung cancer. To examine the possible causal role of IGFs in lung cancer development, we compared plasma levels of IGF-I, IGF-II, and an IGF-binding protein (IGFBP-3) in patients with newly diagnosed lung cancer and in control subjects. METHODS: From an ongoing hospital-based, case-control study, we selected 204 consecutive patients with histologically confirmed, primary lung cancer and 218 control subjects who were matched to the case patients by age, sex, race, and smoking status. IGF-I, IGF-II, and IGFBP-3 plasma levels were measured by enzyme-linked immunosorbent assay and then divided into quartiles, based on their distribution in the control subjects. Associations between the IGF variables and lung cancer risk were estimated by use of odds ratios (ORs). Reported P values are two-sided. RESULTS: IGF and IGFBP-3 levels were positively correlated (all r>.27; all P<.001). High plasma levels of IGF-I were associated with an increased risk of lung cancer (OR = 2.06; 95% confidence interval [CI] = 1.19-3.56; P = .01), and this association was dose dependent in both univariate and multivariate analyses. Plasma IGFBP-3 showed no association with lung cancer risk unless adjusted for IGF-I level; when both of these variables were analyzed together, high plasma levels of IGFBP-3 were associated with reduced risk of lung cancer (OR = 0.48; 95% CI = 0.25-0.92; P = .03). IGF-II was not associated with lung cancer risk. CONCLUSIONS: Plasma levels of IGF-I are higher and plasma levels of IGFBP-3 are lower in patients with lung cancer than in control subjects. If these findings can be confirmed in prospective studies, measuring levels of IGF-I and IGFBP-3 in blood may prove useful in assessing lung cancer risk.

Analysis of Variance↗
PubMed1999

Is there a genetic basis for lung cancer susceptibility?

The major risk factor for lung cancer is exposure to tobacco smoke. Exposure to radon, heavy metals used in smelting, and asbestos also greatly increase risks for lung cancer. However, only about 11% of tobacco smokers ultimately develop lung cancer, suggesting that genetic factors may influence the risk for lung cancer among those who are exposed to carcinogens. Further support for this hypothesis is provided by several epidemiological studies and also from molecular epidemiological studies. Epidemiological studies show approximately 14-fold increased risks for lung cancer among average tobacco smokers and approximately 2.5-fold increased risks attributable to a family history of lung cancer after controlling for tobacco smoke. Segregation analyses suggest that a rare autosomal dominant gene may explain susceptibility to early-onset lung cancer, but these results explain a minority of lung cancer cases, which include a family history. Therefore, more common genetic variants or polymorphisms are hypothesized to affect lung cancer risk. Environmental carcinogenesis resulting from tobacco smoke exposure is a complex process that can involve activation of procarcinogens that lead to adduct formation and subsequent failure of DNA repair, which should normally remove these adducts. Studies comparing DNA repair capacity among newly diagnosed lung cancer patients and age-matched controls indicate significant differences between the two groups. On culturing with bleomycin lymphocytes from lung cancer patients and age- and ethnicity-matched controls, the lymphocytes from lung cancer cases have been consistently observed to show higher levels of chromatid breaks than the control lymphocytes. A similar assay has been developed using benzo-[alpha]pyrene diol-epoxide (BPDE), a reactive substrate that is derived by in vitro processes from benzo[alpha]pyrene, a major carcinogen in tobacco smoke. Results from this assay show an even more significantly higher level of damaged chromatids in lung cancer patients than in controls. Poor DNA repair is independent of tobacco smoking status. The cellular processes involved in DNA repair of bleomycin and BPDE have not yet been fully elaborated. However, the consistency of findings with these two carcinogens indicates that DNA repair capacity influences risk for lung cancer among individuals.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1999

Three measures of mutagen sensitivity in a cancer-free population.

Different individuals appear to respond differently to the same carcinogen, and different mutagens act differently on cells. We conducted mutagen sensitivity assays by using three mutagens (bleomycin, a radiomimetic agent; 4-nitroquinoline-1-oxide [4-NQO], an ultraviolet light mimetic agent; and benzo[a]pyrene diol epoxide [BPDE], a tobacco mutagen) in parallel in healthy human subjects to determine the relationships among these assays. Our results showed that the mean breaks per cell values (b/c) (+/- SD) for bleomycin, 4-NQO, and BPDE sensitivity were 0.49 (+/- 0.26), 0.53 (+/- 0.30), and 0.66 (+/- 0.41), respectively. Age, sex, smoking status, and family history of cancer were not correlated with any of these mutagen sensitivities. Also, there was no correlation between bleomycin and 4-NQO or 4-NQO and BPDE sensitivity, but a weak correlation between bleomycin and BPDE was observed (correlation coefficient = 0.289; P = 0.001). When the 75th percentile of b/c was used as a cutoff point in each assay, only one individual (1.8%) was sensitive to all three mutagens. Ten individuals (17.9%) were sensitive to two mutagens, 20 (35.7%) to one mutagen, and 25 (44.6%) to none of three mutagens. Our study suggests that these three mutagens may involve different DNA damage and repair pathways. The lack of correlation between the assay results may indicate the necessity of using a battery of mutagen sensitivity tests to refine our ability to identify a subpopulation at high cancer risk.

4-Nitroquinoline-1-oxide↗
PubMed1999

Associations among telomerase activity, p53 protein overexpression, and genetic instability in lung cancer.

Genomic instability is a driving force for tumorigenesis. p53 and telomerase play central roles in maintaining genomic integrity. The purpose of this study was to assess the associations among p53 protein overexpression, telomerase activity and genetic instability in lung cancer. We found that telomerase activity was detectable in 80% of 100 lung tumours, but only 7.7% of 91 paired adjacent normal tissues. p53 protein was overexpressed in 63% of the tumours but only 2% of the normal tissues. p53 was overexpressed in 56 of the 80 (70%) tumour tissues with telomerase activity but only seven of the 20 (35%) without telomerase activity. p53 protein overexpression carried a 6.7-fold (95% confidence interval, 1.7-27.7) increased risk for positive telomerase activity after adjustment by age, sex, ethnicity, smoking status and family history of lung cancer. The mean in vitro bleomycin-induced breaks per cell (a marker of cancer susceptibility) was significantly higher (0.92) for patients who overexpressed p53 in lung tumour tissue than that for patients with no detectable p53 expression in lung tumour tissue (0.65). Our data suggest that p53 protein overexpression may be common in individuals genetically susceptible to carcinogen exposure. p53 status may be related to telomerase expression.

Adult↗
PubMed1999

Development of a database for assessing dietary phytoestrogen intake.

For the past two decades, epidemiologists have observed lower risks of lung, breast, prostate, colon, and other cancers in populations that frequently consume fruits and vegetables. Numerous phytoestrogens have been shown to be anticarcinogenic under experimental conditions and may account for at least part of the cancer-prevention effects of fruit and vegetable consumption. These plant constituents include isoflavonoids, coumestans, lignans, phytosterols, and flavonoids. DietSys, the nutrient analysis program associated with the National Cancer Institute Health Habits and History Questionnaire (HHHQ), and other nationally available nutrient analysis databases do not fully assess these constituents. Therefore, we modified DietSys to include these components in foods on the basis of published values. In addition, as part of an epidemiological study of prostate cancer, we modified the food-frequency component of the HHHQ to include the main foods contributing to phytoestrogen intake. Although there are limitations to the consistency and quality of many of the values because they were gathered from a variety of sources, our approach should provide a useful first tool for assessing the epidemiological association between phytoestrogen consumption and cancer risk. Furthermore, this work has already facilitated the identification of the major dietary contributors with phytoestrogen activity and prioritized future laboratory analyses of specific foods toward the development of a more complete and accurate database.

Anticarcinogenic Agents↗
PubMed1999

Phytoestrogen intake and prostate cancer: a case-control study using a new database.

In the last several years, attention has been focused on comparing the Western diet, which is rich in fat, protein, and refined carbohydrates, with the Asian diet, which is rich in phytoestrogens, as a possible explanation for the contrasting rates of clinically relevant prostate cancer. Phytoestrogens, plant-derived nutrients, include several isoflavones, flavonoids, lignans, phytosterols, and coumestans, some of which have been postulated as having anticarcinogenic properties. Using a new database, we examined the role of phytoestrogen intake and prostate cancer risk in 83 Caucasian cases and 107 controls. Controls reported consuming higher amounts of foods containing genistein, daidzein, and coumestrol and lower amounts of foods containing campesterol and stigmasterol. Multivariate analysis, after adjustment for age, family history of prostate cancer, alcohol consumption, and total calorie intake, showed an inverse association between coumestrol (p = 0.03) and daidzein (p = 0.07) and prostate cancer risk. Genistein, the most studied phytoestrogen, showed a slight protective effect (p = 0.26). However, a positive association was found between campesterol (p = 0.08) and stigmasterol (p = 0.03) and risk of prostate cancer. These results are suggestive of a possible relationship between phytoestrogen intake and prostate cancer risk. Larger comprehensive studies are needed to further refine the role of phytoestrogen intake in prostate cancer risk.

Anticarcinogenic Agents↗
PubMed1999

Polymorphisms of DNA repair gene XRCC1 in squamous cell carcinoma of the head and neck.

Because reduced DNA repair capacity (phenotype) has been suggested as a risk factor for squamous cell carcinoma of the head and neck (SCCHN), newly-identified DNA repair gene polymorphisms (genotype) may also be implicated in risk. To test this hypothesis, we conducted a case-control study of 203 SCCHN patients and 424 control subjects (matched for age, sex and ethnicity) to investigate the role of two XRCC1 polymorphisms (XRCC1 26304 T and XRCC1 28152 A, respectively) in SCCHN. Multivariate logistic regression analysis was performed to calculate the adjusted odds ratio (OR) and 95% confidence interval (CI). A total of 180 cases (88.7%) and 363 controls (85.6%) lacked the XRCC1 26304 T allele [adjusted OR = 1.34 (CI, 0.80-2.25)]. Lack of this polymorphism was a significant risk factor specifically for cancers of the oral cavity and pharynx [adjusted OR = 2.46 (CI, 1.22-4.97)]. Thirty-two cases (15.8%) and 46 controls (10.8%) were homozygous for the XRCC1 28152 A allele [adjusted OR = 1.59 (CI, 0.97-2.61) for all cases, and 1.41 (CI, 0. 80-2.48) for oral and pharyngeal cancer only]. Furthermore, when the two genotypes were combined into a three-level model of risk, a polymorphism-polymorphism interaction of increasing risk (trend test, P = 0.049) was evident: OR = 1.0 for those with neither risk genotype (referent group), adjusted OR = 1.51 (CI, 0.87-2.61) for those with either risk genotype, and 2.02 (CI, 1.00-4.05) for those with both risk genotypes. For oral and pharyngeal cancer, this trend was even more pronounced with the adjusted OR = 2.68 (CI, 1.28-5.61) for those with either risk genotype, and 3.22 (CI, 1.33-7.81) for those with both risk genotypes. The findings support the hypothesis that a polymorphic XRCC1 DNA repair gene contributes to risk of developing SCCHN.

Base Sequence↗
PubMed1999

Ethnic differences in poly(ADP-ribose) polymerase pseudogene genotype distribution and association with lung cancer risk.

Poly(ADP-ribose) polymerase (PADPRP) is a nuclear DNA-binding enzyme that can modulate chromatin structure close to DNA replication, recombination and repair regions. Two-allele polymorphism on the PADPRP chromosome 13 pseudogene has been studied in several ethnic subpopulations, and the association of each allele with different types of cancer has been investigated. To study the frequency of the allele in the context of lung cancer, we performed a PCR assay for the PADPRP polymorphism in 288 lung cancer patients and 292 matched controls and examined the frequency of the alleles in different ethnic groups. Our results showed that the allele distribution was significantly different among members of different ethnic groups. Specifically, the A allele was dominant in Mexican-American and Caucasian groups but not in the African-American group. The frequencies of the B allele in Mexican-American, Caucasian and African-American controls were 0.184, 0.218 and 0.606, respectively, with the Caucasian cases and controls showing an almost identical lower B allele frequency (0.199 in cases versus 0.218 in controls), and the African-American cases and controls showing an almost identical but considerably higher frequency (0.578 in cases versus 0. 606 in controls). In contrast, the Mexican-American cases and controls exhibited a considerable difference in the B allele frequency (0.306 in cases versus 0.184 in controls). When we combined subjects with the AB or BB genotype into a susceptible genotype group and compared them with the AA group using univariate analysis, the susceptible genotype was not shown to be associated with a risk of lung cancer in either the Caucasian or African-American subpopulation but was significantly associated with an increased risk (2.29-fold) of lung cancer in the Mexican-American group. When lung cancer was categorized by histologic type, no elevated risk was noted for squamous cell carcinoma in any ethnicity. However, in Mexican-Americans, susceptible genotypes were associated with significantly increased risks of adenocarcinoma (3. 21-fold) and large cell carcinoma (10.79). Our study and others have demonstrated that the PADPRP polymorphism may modify an individual's susceptibility to certain cancers. Assessment of the interaction between genetic constitution and environmental exposure might expand our understanding of carcinogenesis and enhance our ability to evaluate the populational cancer risk.

Adenocarcinoma↗