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J F Fraumeni

Publications and source records attributed to J F Fraumeni.

At least 19 recordsLinked to original sources
PubMed2006

Polymorphisms in Th1-type cell-mediated response genes and risk of gastric cancer.

Helicobacter pylori infection, the dominant risk factor for gastric cancers, has been shown to elicit T helper type 1 (Th1) polarized immunological responses. We conducted a population-based study of 305 gastric cancer cases and 427 age- and gender-matched controls in Warsaw, Poland, to evaluate the association with several variants in genes responsible for Th1-cell-mediated response. Genotyping was performed on genomic DNA by TaqMan(TM) assays to determine TNFA (-308 G>A, -417 G>A, -555 G>A, -1036 C>T, -1042 C>A, -1210 T>C), IL1A (-889 C>T), IFNGR2 (Ex7-128 T>C, Ex2-34 C>G and Ex2-16 A>G) and IL12A (IVS2-798 T>A, IVS2-701 C>A and Ex7+277 G>A) polymorphisms. We used unconditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for sex, age, education and smoking status. Out of six single nucleotide polymorphisms (SNPs) tested in TNFA, gastric cancer risk was significantly associated with the TNFA (-308 G>A) polymorphism, with ORs of 1.4 (95% CI: 1.0-2.0) for the G/A and 2.5 (95% CI: 1.3-4.9) for the A/A genotype carriers, when compared with the more frequent genotype (G/G) (P-trend < 0.001). Among the three tested SNPs in the IFNGR2 gene, only the Ex7-128C>T polymorphism was associated with increased risk, with ORs of 1.5 (95% CI: 1.0-2.3) for T/C and 1.7 (95% CI: 1.1-2.7) for C/C carriers when compared with T/T carriers (P-trend = 0.01). Subjects carrying both IFNGR2 Ex7-128 C/C and TNFA -308 A/A genotypes had the highest risk (OR = 5.5, 95% CI: 1.5-19.4), although the interaction was not statistically significant. IL1A (-889 C>T) and the three examined IL12A variants were unrelated to gastric cancer risk. Our findings suggest that two Th1-related polymorphisms (TNFA -308 A>G and IFNGR2 Ex7-128 C>T) may increase the risk of gastric cancer.

Adult↗
PubMed2005

Risk of prostate cancer and family history of cancer: a population-based study in China.

We evaluated prostate cancer risk and family history of cancers using data from a case-control study in China. Cancer information among first-degree relatives was collected from 709 subjects (238 cases and 471 controls). None of the subjects reported a family history of prostate cancer. However, excess prostate cancer risk was associated with a family history of any cancer (OR = 1.79, 95% CI: 1.21-2.63) and esophageal cancer (OR = 2.39, 95% CI: 1.15-5.00). Nonsignificant risk was seen for family history of cancers of the stomach, lung, and female breast. Our results did not confirm the familial tendency toward prostate cancer but other cancers prevalent in China appeared to be aggregate, particularly esophageal cancer. Larger studies are needed to confirm these findings, and to clarify the genetic and lifestyle factors that may be involved.

Aged↗
PubMed2003

Lung cancer after treatment for Hodgkin's disease: focus on radiation effects.

Aspects of radiation-induced lung cancer were evaluated in an international study of Hodgkin's disease. The study population consisted of 227 patients with lung cancer and 455 matched controls. Unique features included dose determinations to the specific location in the lung where each cancer developed and quantitative data on both chemotherapy and tobacco use obtained from medical records. The estimated excess relative risk (ERR) per Gy was 0.15 (95% CI: 0.06-0.39), and there was little evidence of departure from linearity even though lung doses for the majority of Hodgkin's disease patients treated with radiotherapy exceeded 30 Gy. The interaction of radiation and chemotherapy that included alkylating agents was almost exactly additive, and a multiplicative relationship could be rejected (P = 0.017). Conversely, the interaction of radiation and smoking was consistent with a multiplicative relationship, but not with an additive relationship (P < 0.001). The ERR/Gy for males was about four times that for females, although the difference was not statistically significant. There was little evidence of modification of the ERR/Gy by time since exposure (after a 5-year minimum latent period), age at exposure, or attained age. Because of the very high radiation doses received by Hodgkin's disease patients and the immunodeficiency inherent to this lymphoma and that associated with chemotherapy, generalizing these findings to other populations receiving considerably lower doses of radiation should be done cautiously.

Adult↗
PubMed2002

Acromegaly and cancer risk: a cohort study in Sweden and Denmark.

OBJECTIVE: Several studies have suggested that patients with acromegaly have an increased risk of benign and malignant neoplasms, especially of the colon. To further investigate this relationship we evaluated cancer risk in population-based cohorts of acromegaly patients in Sweden and Denmark. METHODS: Nationwide registry-based cohorts of patients hospitalized for acromegaly (Denmark 1977-1993; Sweden 1965-1993) were linked to tumor registry data for up to 15-28 years of follow-up, respectively. Standardized incidence ratios (SIR) and 95% confidence intervals (CI) were calculated to estimate cancer risk among 1634 patients with acromegaly. RESULTS: The patterns of cancer risk in Sweden and Denmark were similar. After excluding the first year of follow-up, 177 patients with acromegaly had a diagnosis of cancer compared with an expected number of 116.5 (SIR = 1.5. 95% CI = 1.3-1.8). Increased risks were found for digestive system cancers (SIR = 2.1, 95% CI = 1.62.7), notably of the small intestine (SIR = 6.0, 95% CI = 1.2-17.4), colon (SIR = 2.6, 95% CI = 1.6-3.8), and rectum (SIR = 2.5, 95% CI= 1.3-4.2). Risks were also elevated for cancers of the brain (SIR = 2.7, 95% CI= 1.2-5.0). thyroid (SIR = 3.7, 95% CI = 1.8-10.9), kidney (SIR = 3.2, 95% CI = 1.6-5.5), and bone (SIR= 13.8, 95% CI= 1.7-50.0). CONCLUSIONS: The increased risk for several cancer sites among acromegaly patients may be due to the elevated proliferative and anti-apoptotic activity associated with increased circulating levels of insulin-like growth factor-1 (IGF-1). Pituitary irradiation given to some patients may have contributed to the excess risks of brain tumors and thyroid cancer. Our findings indicate the need for close medical surveillance of patients with acromegaly, and further studies of the IGF-I system in the etiology of various cancers.

Acromegaly↗
PubMed2002

Global increases in kidney cancer incidence, 1973-1992.

Reports of increasing rates for kidney cancers in several count prompted this analysis of global incidence trends for total kidney cancers and by subsite. International incidence data for 5-year periods 1973-1977, 1978-1982, 1983-1987 and 1988-1992 were obtained from volumes IV to VII of Cancer Incidence in Five Continents published by the International Agency for Research on Cancer. The USA data for the same 5-year periods were obtained from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute. Percentage changes in incidence rates were computed using the relative difference between the time periods 1973-1977 and 1988-1992, and annual percentage changes in incidence rates were computed using log linear regression. In 1988-1992, kidney cancer incidence rates (age-adjusted to the world-standard population) were highest in France (16.1/100,000 man-years and 7.3/100,000 woman-years) and lowest in India (2.0 and 0.9, respectively). Between 1973-1977 and 1988-1992, incidence rates rose among men and women in all regions and ethnic groups, with a few exceptions, mostly in Scandinavian countries. The largest percentage increase for men was in Japan (171%) and for women in Italy (107%). Rates for renal pelvis cancer were less than 1/100,000 person-years in almost all regions in both sexes, and the temporal trends were inconsistent. Incidence trends for renal parenchyma cancer tracked those for total kidney cancers, and appeared to result from increases in the prevalence of risk factors and in use of diagnostic imaging procedures.

Americas↗
PubMed2002

Cigarette and alcohol consumption and the risk of colorectal cancer in Shanghai, China.

The relation of cigarette smoking and alcohol drinking to colorectal cancer risk has been inconsistent in the epidemiological literature. In a population-based case-control study of colorectal cancer in Shanghai, China, where the incidence rates are rising sharply, we examined the association with tobacco and alcohol use. Cases were aged 30-74 years and newly diagnosed with cancers of the colon (N = 931) or rectum (N = 874) between 1990 and 1992. Controls (N = 1552) were randomly selected among Shanghai residents, frequency-matched to cases by gender and age. Information on lifetime consumption of tobacco and alcohol, as well as demographic and other risk factors, was obtained through in-person interviews. Associations with cigarette smoking and alcohol use were estimated by odds ratios (ORs) and 95% confidence intervals (CIs). Among women, the prevalence of smoking and alcohol drinking was low, and no significant association with colon or rectal cancer was observed. Although cigarette smoking among men was not related overall to colon or rectal cancer risk, there was a 50% excess risk of rectal cancer (OR 1.5, 95% CI 0.9-2.5) among those who smoked 55 or more pack-years. Among men, former alcohol drinkers had an increased risk of colon cancer (OR 2.3, 95% CI 1.4-3.7) but not rectal cancer, while current drinkers had a 30-50% excess risk of colon cancer only among those with long-term (30+ years) and heavy (>560 g ethanol/week) consumption. The excess risks were mainly associated with hard liquor consumption, with no material difference in risk between proximal and distal colon cancer. Although cigarette smoking and alcohol drinking in general were not risk factors for colorectal cancers in Shanghai, there were small excess risks for rectal cancer among heavy smokers and colon cancer among heavy drinkers.

Adult↗
PubMed2001

Family cancer history and susceptibility to oral carcinoma in Puerto Rico.

BACKGROUND: Use of alcohol and tobacco are the major risk factors for cancers of the oral cavity and pharynx in most of the world. A heritable component to oral carcinoma risk also has been suggested, although only limited data are available on familial aggregation of this disease. METHODS: A population-based case-control study of 342 subjects with carcinomas of the oral cavity and pharynx (oral carcinoma) and 521 controls was conducted in Puerto Rico. The relation between family history of carcinomas of the oral cavity, the upper aerodigestive tract (UADT), and other selected sites with risk of oral carcinoma was explored using logistic regression modeling techniques. RESULTS: Risk of oral carcinoma was elevated for subjects reporting a first-degree relative with carcinoma of the oral cavity (odds ratio [OR], 2.5; 95% confidence interval [CI], 0.8-8.0) or any UADT carcinoma (OR, 2.6; 95% CI, 1.4-4.8). The increased risk associated with family history of UADT carcinoma tended to be greatest for subjects with known risk factors (i.e., heavy consumption of alcohol and/or tobacco and infrequent intake of raw fruits and vegetables) and with oral carcinoma diagnoses at ages younger than 65 years. CONCLUSIONS: These findings are consistent with a heritable component to oral carcinoma, although shared lifestyle risk factors may be partially involved.

Adult↗
PubMed2001

International trends and patterns of primary liver cancer.

Primary liver cancer (PLC) is common in many areas of the developing world, but uncommon in most of the developed world. Some evidence suggests, however, that the global pattern of PLC may be changing. To clarify this issue, we examined incidence rates for PLC over the 15-year time period, 1978-92, in selected cancer registries around the world. With some exceptions, developed countries have experienced PLC increases in incidence whereas developing countries have experienced declines. Although the reasons for the trends are not entirely clear, the increased seroprevalence of HCV in the developed world and the elimination of HBV-cofactors in the developing world are likely to have contributed to the patterns. Further progress against PLC may be seen in the developing world once the HBV-vaccinated segment of the population reaches adulthood. Published 2001 Wiley-Liss, Inc.

Aflatoxin B1↗
PubMed2001

Nationwide study of cancer risk among hip replacement patients in Sweden.

BACKGROUND: Orthopedic implants and their fixatives contain materials with carcinogenic potential. Whether these implants are linked to subsequent cancer development remains unknown, mainly because large-scale, long-term follow-up data are scarce. METHODS: We conducted a nationwide cohort study in Sweden to examine cancer incidence among 116,727 patients who underwent hip replacement surgery during the period from 1965 through 1994. Through record linkage to the Swedish Cancer Register, we identified all incident cancers through 1995 in this population (693,954 person-years of observation). For each cancer type, the observed number of cases was divided by that expected in the general Swedish population to produce standardized incidence ratios (SIRs). RESULTS: Relative to the general population, the cohort had no overall cancer excess (SIR = 1.01; 95% confidence interval [CI] = 0.99 to 1.03). However, we observed elevated SIRs for prostate cancer (SIR = 1.16; 95% CI = 1.11 to 1.22) and melanoma (SIR = 1.15; 95% CI = 1.01 to 1.30) and a reduction in stomach cancer risk (SIR = 0.83; 95% CI = 0.75 to 0.92). Long-term follow-up (>or=15 years) revealed an excess of multiple myeloma (SIR = 1.86; 95% CI = 1.01 to 3.11) and a statistically nonsignificant increase in bladder cancer (SIR = 1.42; 95% CI = 0.98 to 1.99). There was no material increase in risk for bone or connective tissue cancer for either men or women in any follow-up period. CONCLUSIONS: In this, the largest study to date, hip implant patients had similar rates of most types of cancer to those in the general population. Although the excesses of melanoma, multiple myeloma, and prostate and bladder cancers may be due to chance, confounding, or detection bias and should be interpreted cautiously, they warrant further investigation because of the ever-increasing use of hip implants at younger ages.

Aged↗
PubMed2001

Solid tumors after chronic lymphocytic leukemia.

Prior reports indicate that patients with chronic lymphocytic leukemia (CLL) may be at increased risk of subsequent neoplasms. This study quantified the risk of second cancers among 16 367 patients with CLL in the population-based Surveillance, Epidemiology and End Results Program. Overall, the observed/expected ratio (O/E) was 1.20 (95% confidence interval [CI], 1.15-1.26). Second cancer risks for patients who received chemotherapy only as the first course of treatment (O/E = 1.21) were similar to risks for those who received no treatment initially (O/E = 1.19). Significant excesses were found for Kaposi sarcoma (O/E = 5.09), malignant melanoma (O/E = 3.18), and cancers of the larynx (O/E = 1.72) and the lung (O/E = 1.66). Increased risks were also found for brain cancer among men (O/E =1.91) and for cancers of the stomach (O/E = 1.76) and bladder (O/E = 1.52) among women. Additional investigations of cancers after CLL are needed to explore the role of immunologic impairment and/or other etiologic influences.

Aged↗
PubMed2001

Red meat, family history, and increased risk of gastric cancer with microsatellite instability.

Microsatellite instability (MSI) occurs frequently in sporadic gastric cancer (GC) and may define a distinctive molecular pathway of carcinogenesis. We evaluated the role of dietary risk factors in GC according to MSI status. A large series of 382 GC cases and 561 controls were originally identified in a population-based case-control study carried out in the high-risk area around Florence, Italy; 126 GC patients were typed for MSI status. A MSI+ phenotype was detected in 43 of 126 cases (34.1%), whereas 83 cases were classified as MSI-. A multinomial logistic regression model was used to compare the two subgroups of GC classified according to MSI status in the same analysis, with all of the available population controls. A case-case approach was also used. The risk of MSI+ tumors was positively associated with high consumption of red meat and meat sauce and negatively associated with consumption of white meat. A positive association was also seen with total protein and nitrite intake, whereas no relation was found with micronutrient intake. Risk was especially high among subjects reporting both a positive GC family history and a high consumption of red meat (odds ratio, 25.7; 95% confidence interval, 6.4-102.8). For MSI- tumors, a significant protective effect was associated with frequent consumption of citrus and other fresh fruit, garlic, legumes, vegetables, and olive oil and with high intake of beta-carotene and other antioxidants and sugar, whereas positive associations were seen with protein and sodium intake. In summary, a specific dietary pattern emerged for MSI+ gastric tumors, suggesting that factors related to red meat consumption are involved in this pathway, particularly among individuals with a positive family history. In contrast, the risk of MSI- tumors was strongly reduced by the frequent consumption of fresh fruit and vegetables.

Aged↗
PubMed2001

Family history of cancer and risk of esophageal and gastric cancers in the United States.

The worldwide rates for histology- and subsite-specific types of esophageal and gastric cancer reveal strikingly divergent patterns. The contribution of environmental and genetic factors has been explored in several high-incidence areas, but data on genetic influences are scarce for Western countries. Using data from a multicenter, population-based, case-control study on 1,143 cases and 695 controls in the United States, we evaluated whether a family history of digestive or other cancers was associated with an increased risk of esophageal adenocarcinoma (n = 293), esophageal squamous cell carcinoma (n = 221), gastric cardia adenocarcinoma (n = 261) or non-cardia gastric adenocarcinoma (n = 368). After adjusting for other risk factors, individuals reporting a family history of digestive cancers experienced no increased risk of either type of esophageal cancer but they were prone to adenocarcinomas of the gastric cardia [odds ratio (OR) = 1.34, 95% confidence interval (CI) 0.91-1.97] and non-cardia segments (OR =1.46, 95% CI 1.03-2.08). This familial tendency, particularly for non-cardia gastric tumors, was largely explained by an association with family history of stomach cancer (OR = 2.52, 95% CI 1.50-4.23). In addition, family history of breast cancer was associated with increased risks of esophageal adenocarcinoma (OR = 1.74, 95% CI 1.07-2.83) and non-cardia gastric adenocarcinoma (OR = 1.76, 95% CI 1.09-2.82). Also seen were non-significant familial associations of esophageal squamous-cell cancer with prostate cancer as well as non-cardia gastric cancer with leukemia and brain tumors, though these relationships must be interpreted with caution. Our data point to the role of familial susceptibility to gastric cancer, but not to any form of esophageal cancer, in the United States.

Adenocarcinoma↗
PubMed2001

Vitamin D receptor gene polymorphisms, insulin-like growth factors, and prostate cancer risk: a population-based case-control study in China.

Operating through the vitamin D receptor (VDR), vitamin D inhibits prostate cancer growth and increases insulin-like growth factor binding protein (IGFBP) expression, suggesting that the vitamin D and insulin-like growth factor (IGF) regulatory systems may operate together to affect prostate cancer. Among 191 newly diagnosed prostate cancer cases and 304 randomly selected population controls in Shanghai, China, we found no significant association between the BsmI or FokI VDR gene polymorphisms and prostate cancer risk. However, we found that among men with the ff FokI genotype, those in the highest tertile of plasma IGFBP-3 had a decreased risk versus those in the lowest tertile (odds ratio, 0.14; 95% confidence interval, 0.04-0.56; P(trend) < 0.01), whereas among men with the FF and Ff genotypes, IGFBP-3 was not associated with risk. Similarly, IGFBP-1 was inversely associated with prostate cancer risk only among men with the ff FokI genotype (odds ratio, 0.25; 95% confidence interval, 0.07-0.85; P(trend) = 0.02). No such FokI genotype-specific effects were observed for IGF-I or IGF-II. Our findings in a low-risk population suggest that the IGF and vitamin D regulatory systems may interact to affect prostate cancer risk. Larger studies are needed to confirm these findings and clarify the underlying mechanisms.

Adolescent↗
PubMed2001

Beta-catenin mutations in biliary tract cancers: a population-based study in China.

beta-Catenin is an ubiquitously expressed cytoplasmic protein that has a crucial role in both cadherin-mediated cell-cell adhesion and as a downstream signaling molecule in the wingless/Wnt pathway. Activating mutations in exon 3 of the beta-catenin gene, at the phosphorylation sites for ubiquitination and degradation of beta-catenin, are present in a variety of cancers. Because alterations of the adenomatous polyposis coli (APC) gene are present in biliary tract cancers and the APC protein modulates levels of beta-catenin, we evaluated the role of beta-catenin in biliary tract cancer by sequencing the third exon of the beta-catenin gene among 107 biliary tract cancers and 7 gallbladder adenomas from a population-based study in CHINA: Point mutations of serine or threonine phosphorylation sites in exon 3 of beta-catenin were present in 8 of 107 (7.5%) biliary tract cancers and 4 of 7 (57.1%) gallbladder adenomas. Mutations of beta-catenin were more frequent in ampullary and gallbladder carcinomas than in bile duct carcinomas (P = 0.04) and in papillary adenocarcinomas than other histological types of carcinomas (P = 0.02). These results suggest that the molecular pathways of biliary tract neoplasms vary by anatomical subsite and histological subtype.

Adenoma↗
PubMed2001

Breast cancer risk in relation to amount of tissue removed during breast reduction operations in Sweden.

BACKGROUND: Women who undergo breast reduction operations have substantially lowered risks of breast cancer, and the reasons remain unclear. The current investigation attempted to assess whether the reduction in breast cancer risk was related directly to the amount of breast tissue removed. METHODS: Medical record retrieval was attempted for 161 breast cancer patients in a Swedish cohort of 31,910 women who had had breast reduction surgery and for 483 women who had not developed breast cancer. Information on amount of breast tissue removed was abstracted along with other factors that influence breast cancer risk. Odds ratios of developing breast cancer were calculated based on amount of breast tissue removed. RESULTS: The amount of tissue removed was a significant predictor of risk, as subjects in the highest quartile of tissue removal had a significantly lower risk than those in the lowest quartile. Considering the total amount of tissue removed (both breasts), subjects with > or = 1600 versus < 800 grams removed had an odds ratio (OR) of 0.24 [95% confidence interval (CI) 0.1-0.5]. This relation persisted after adjustment for other breast cancer risk factors and was apparent within every subgroup examined. CONCLUSIONS: The finding that breast cancer risk was reduced in proportion to the amount of tissue removed should be reassuring to women who are considering breast reduction procedures and to women who are electing to have bilateral total prophylactic mastectomies because of a strong genetic predisposition.

Adolescent↗
PubMed2001

Excess incidence of squamous cell esophageal cancer among US Black men: role of social class and other risk factors.

Data from a population-based case-control study were used to evaluate the relation between social class factors and squamous cell esophageal cancer and the extent to which alcohol, tobacco, diet, and low income contribute to the higher incidence among Black men than among White men in the United States. A total of 347 male cases (119 White, 228 Black) and 1,354 male controls (743 White, 611 Black) were selected from three US geographic areas (Atlanta, Georgia, Detroit, Michigan, and New Jersey). Cases were residents of the study areas aged 30-79 years who had been diagnosed with histologically confirmed esophageal cancer between 1986 and 1989. The adjusted odds ratios for subjects with annual incomes less than $10,000 versus incomes of $25,000 or more were 4.3 (95% confidence interval: 2.1, 8.7) for Whites and 8.0 (95% confidence interval: 4.3, 15.0) for Blacks. The combination of all four major risk factors-low income, moderate/heavy alcohol intake, tobacco use, and infrequent consumption of raw fruits and vegetables-accounted for almost all of the squamous cell esophageal cancers in Whites (98%) and Blacks (99%) and for 99% of the excess incidence among Black men. Thus, lifestyle modifications, especially a lowered intake of alcoholic beverages, would markedly decrease the incidence of squamous cell esophageal cancer in both racial groups and would narrow the racial disparity in risk. Further studies on the determinants of social class may help to identify a new set of exposures for this tumor that are amenable to intervention.

Adult↗
PubMed2001

The use of common genetic polymorphisms to enhance the epidemiologic study of environmental carcinogens.

Overwhelming evidence indicates that environmental exposures, broadly defined, are responsible for most cancer. There is reason to believe, however, that relatively common polymorphisms in a wide spectrum of genes may modify the effect of these exposures. We discuss the rationale for using common polymorphisms to enhance our understanding of how environmental exposures cause cancer and comment on epidemiologic strategies to assess these effects, including study design, genetic and statistical analysis, and sample size requirements. Special attention is given to sources of potential bias in population studies of gene--environment interactions, including exposure and genotype misclassification and population stratification (i.e., confounding by ethnicity). Nevertheless, by merging epidemiologic and molecular approaches in the twenty-first century, there will be enormous opportunities for unraveling the environmental determinants of cancer. In particular, studies of genetically susceptible subgroups may enable the detection of low levels of risk due to certain common exposures that have eluded traditional epidemiologic methods. Further, by identifying susceptibility genes and their pathways of action, it may be possible to identify previously unsuspected carcinogens. Finally, by gaining a more comprehensive understanding of environmental and genetic risk factors, there should emerge new clinical and public health strategies aimed at preventing and controlling cancer.

Animals↗