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PubMed1997

Family history of cancer and risk of lung cancer in lifetime non-smokers and long-term ex-smokers.

BACKGROUND: Genetic factors appear to play a role in the aetiology of lung cancer. METHODS: To examine the association between family history of cancer (all types) and risk of lung cancer among non-smokers, we conducted a case-control study. Cases (n = 618) were identified through the Missouri Cancer Registry for the period 1986 through 1991, and included 432 lifetime non-smokers and 186 ex-smokers who had stopped at least 15 years prior to diagnosis or had smoked for less than one pack-year. Controls (n = 1402) were selected through drivers licence and Medicare files. RESULTS: The risk of lung cancer increased directly in relation to the number of family members affected with cancer. The odds ratio (OR) associated with five or more first-degree relatives with cancer was 2.7 (95% confidence interval [CI] 1.2-6.1), with a significant linear trend in risk according to the number of relatives affected (P = 0.03). Increased lung cancer risk was associated with two or more affected siblings (OR = 1.4; 95% CI: 1.0-1.9) and with two or more affected offspring (OR = 3.2: 95% CI: 1.3-8.1). Risk was slightly elevated for family history of lung cancer (OR = 1.3; 95% CI: 1.0-1.8). CONCLUSIONS: Our study identified a slight increase in risk of lung cancer in relation to five or more relatives with cancer. Preventive implications of this increased risk are unclear because the attributable fraction is low in comparison to a variety of other factors.

Adult↗
PubMed1999

Increased urinary excretion of 8-oxo-2'-deoxyguanosine, a biomarker of oxidative DNA damage, in urban bus drivers.

Oxidative damage to DNA could be involved in the increased risk of cancer associated with exposure to polluted urban air, which contains a number of oxidants. CYP1A2 is induced by and metabolizes polyaromatic hydrocarbons (PAH) and aromatic amines and could modify effects of exposure to ambient air pollution. Similarly, DNA repair may be influenced by occupational and other exposures as well as modify the effect of DNA damaging agents. As part of a large investigation of the genotoxic burden to diesel exposed workers in transport sectors we studied oxidative DNA damage in 57 non-smoking bus drivers from the greater Copenhagen area. The drivers were studied on a workday and on a day off work. Comparisons were made between drivers from the central (n=30) and rural/suburban (n=27) areas of Copenhagen. The rate of oxidative DNA damage was estimated from 24 h urinary excretion of 8-oxo-2'-deoxyguanosine (8-oxodG), a repair product of the highly mutagenic oxidation of guanine in DNA or the cellular pool of GTP. CYP1A2 activity was estimated from the urinary excretion of metabolites of dietary caffeine. The DNA repair was estimated by unscheduled DNA synthesis (UDS) in mononuclear cells isolated on the workday. Repeated measures ANOVA and multifactorial ANCOVA with CYP1A2 activity, age and UDS as covariates were used for statistical evaluation. On the workday, the 8-oxodG excretion was 190+/-108 and 146+/-89 pmol/kg 24 h in the bus drivers from central and the suburban/rural areas Copenhagen, respectively (p<0.05). The 8-oxodG excretion was not significantly different between the workday and the day off. CYP1A2 activity was not affected by driving area but was correlated with the 8-oxodG excretion on the workday (r=0.53; p<0.05). UDS was not significantly affected by driving area or correlated with the 8-oxodG excretion. The increased excretion of 8-oxodG in bus drivers from central Copenhagen as compared with drivers from rural/suburban greater Copenhagen suggests that exposure to ambient air pollution causes oxidative damage to DNA. This effect may be modified by the activity of CYP1A2 or a coregulated enzyme.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2004

A reevaluation of the literature regarding the health assessment of diesel engine exhaust.

While the International Agency for Research on Cancer (IARC) classified diesel exhaust (DE) as a"probable"carcinogen in 1989 based primarily on"sufficient"animal data, other investigators have since concluded that the lung tumors found in the rat studies were a result of particle overloading. Subsequent health risk assessments of DE have not used the rat cancer data. The U.S. Environmental Protection Agency (EPA), in developing its 2002 Health Assessment Document (HAD) for DE, primarily considered the epidemiology studies of railroad workers and truck drivers to develop health risk assessments of DE. However, both sets of epidemiology studies have serious weaknesses that make them unsuitable for cancer risk assessment. Major shortcomings were the lack of contemporaneous measurements of exposures to DE, difficulties with exposure history reconstruction, and adequately accounting for other exposures such as gasoline exhaust and cigarette smoke. To compound these problems, there was not, and there is still not, a specific exposure marker for DE. Interestingly, in the underground mining industry, where diesel exposures are much higher than observed in railroad workers and truck drivers, there was no increase in lung cancer. These problems and concerns led the U.S. EPA to conclude that while DE was a"likely"carcinogen, a unit risk value or range of risk cannot be calculated from existing data and that the risk could be zero. In addition, the DE emissions have changed and continue to change with the implementation of new emission control technologies. The HAD recognized this fact and noted that further studies are needed to assess new diesel engine emissions. Recent chemical characterization studies on low-emitting diesel engines with catalyzed particulate filters have shown emissions rates for several chemicals of concern that are even lower than comparable compressed natural gas (CNG)-fueled engines. With lower emissions, better fire safety, and improved cost-effectiveness of new low-emitting diesels compared to CNG, current efforts to restrict use of low-emitting diesels seems misguided.

Air Pollutants↗
PubMed2000

Weight change and risk of postmenopausal breast cancer (United States).

OBJECTIVE: Although many studies have shown that higher weight increases the risk of postmenopausal breast cancer, some aspects of this association are unclear. In order to examine the risk associated with different patterns of weight change, we analyzed data from a large case-control study of postmenopausal breast cancer. METHODS: Participants included women aged 50 79 years (n = 5031) who are newly diagnosed with invasive breast cancer in Massachusetts, New Hampshire, and Wisconsin. Similarly-aged population controls (n = 5255) were selected at random from driver's license files and Medicare beneficiary lists. Height, weight, and information on other breast cancer risk factors were ascertained by structured telephone interviews from 1992 to 1995, and logistic regression was used to estimate multivariable-adjusted odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Women in the top quintile groups for height at age 20, recent weight, and recent body mass index had significantly increased risks of breast cancer. Among women who reached their highest adult weight at younger ages (<45 years), increasing weight loss since that age was associated with a reduced risk of postmenopausal breast cancer (OR 0.90, CI 0.84 0.98, per 5 kg). However, weight loss among women whose highest weight occurred after age 45 was not associated with risk (OR 1.00, CI 0.95 1.05, per 5 kg). Weight gain since the lowest adult weight increased risk by 8% for each 5 kg of gain (OR 1.08, CI 1.06-1. 11). Temporary weight cycling (weight loss followed by weight gain) was not associated with increased risk. CONCLUSIONS: Weight gain clearly increased risk of postmenopausal breast cancer. These data lend further support to efforts aimed at helping women avoid weight gain as they age.

Aged↗
PubMed2026

Integrated multi-omics analysis and functional experiments reveals PPAP2C as a potential prognostic biomarker and therapeutic target in breast cancer.

BACKGROUND: This study aims to systematically elucidate the clinical significance and biological function of the phospholipid phosphatase (PLPP) family member (PPAP2C) phosphatidic acid phosphatase type 2C in breast cancer, and to evaluate its potential as a prognostic biomarker and therapeutic target. METHODS: Gene expression data from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Cancer Cell Line Encyclopedia (CCLE) databases were integrated to characterize the expression profile of PLPP family members, focusing on PPAP2C in breast cancer. The prognostic value of PPAP2C, initially identified at the mRNA level (TCGA, (METABRIC) Molecular Taxonomy of Breast Cancer International Consortium, Gene Expression Omnibus (GEO)), was confirmed at the protein level by immunohistochemistry (IHC) on tissue microarrays (TMA). The oncogenic functions of PPAP2C were investigated in triple-negative breast cancer (TNBC) cells through CRISPR-Cas9-mediated knockout and ectopic overexpression, with assessment of key phenotypes including proliferation, colony formation, migration, and invasion. In vivo validation was subsequently performed using an MDA-MB-231 xenograft model. RESULTS: PPAP2C exhibits the most significant overexpression pattern across 33 cancer types (upregulated in 16 cancers, downregulated in only 3). Compared with normal tissues, PPAP2C showed specific overexpression in breast cancer tissues and was significantly associated with advanced clinical stages and aggressive subtypes (HER2+ and TNBC). Survival analysis demonstrated that high PPAP2C expression correlated with significantly shorter overall survival and disease-free survival, which was further validated in METABRIC and GEO cohorts. Tissue microarray analysis confirmed higher PPAP2C protein positivity in tumor tissues (94.7%) than in adjacent normal tissues (59.7%), with worse OS and RFS in high-expression groups. Multivariate analysis identified PPAP2C as an independent prognostic factor for OS. Functional experiments revealed that PPAP2C knockout (via 5-bp/1-bp frameshift mutations) suppressed TNBC cell proliferation, colony formation, migration, and invasion, while overexpression enhanced these phenotypes. In vivo studies further demonstrated complete tumor regression in MDA-MB-231 xenografts upon PPAP2C knockout. CONCLUSION: This study identifies PPAP2C as a key oncogenic driver and a robust independent prognostic biomarker in breast cancer. The findings provide compelling evidence that PPAP2C represents a promising therapeutic target, offering a new strategic avenue for precision therapy, particularly for aggressive breast cancer subtypes.

PLPP2↗
PubMed1997

Breast cancer risk and alcohol consumption: results from a large case-control study.

BACKGROUND: Alcohol use is associated with breast cancer in many epidemiological studies. Most, however, have measured risk from recent consumption patterns, and only a few include analyses for duration of drinking or age that a woman started to drink. The authors studied the effect of these variables, as well as of recent alcohol consumption patterns, on breast cancer risk. METHODS: Data from a large case-control study conducted in Long Island, New York from 1 January 1984 to 31 December 1986 were used. A total of 1214 women aged 20-79 years with incident breast cancer were interviewed. A control was selected for each case from driver's license files, and matched on age and county of residence. Alcohol consumption was measured as: ever versus never, grams of alcohol per day, age started drinking, and total years drinking. RESULTS: After adjustment for breast cancer risk factors, the odds ratio for ever versus never drinking was 1.40 (95% confidence interval [CI] 1.09-1.79); odds ratios for > 0-5 and > or = 5 grams of alcohol use per day, as compared to nondrinkers, were 1.29 (95% CI: 1.00-1.65) and 1.46 (95% CI: 1.13-1.89), respectively. Age when drinking began was not related to breast cancer risk, but the greater the total years of drinking, up to 40 years (odds ratio 1.48, 95% CI: 1.13-1.93), the greater the risk. However, when grams per day and duration of drinking were simultaneously included in the multivariate model, duration was not important as a risk factor. This suggests that intensity of drinking may be the important factor for breast cancer risk. After covariate adjustment, risk from alcohol intake did not differ between pre- and postmenopausal women.

Adult↗
PubMed2025

BOGO: A Proteome-Wide Gene Overexpression Platform for Discovering Rational Cancer Combination Therapies.

Cancer drug resistance remains a major barrier to durable treatment success, often leading to relapse despite advances in precision oncology. While combination therapies are being increasingly investigated, such as chemotherapy with small molecule inhibitors, predicting drug response and identifying rational drug combinations based on resistance mechanisms remain major challenges. Therefore, a proteome-wide, single-gene overexpression screening platform is essential for guiding rational therapy selection. Here, we present BOGO (Bxb1-landing pad human ORFeome-integrated system for a proteome-wide Gene Overexpression), a robust, scalable, and reproducible screening platform that enables single-copy, site-specific integration and overexpression of ~19,000 human open across cancer cell models. Using BOGO, we identified drug-specific response drivers for 16 chemotherapeutic agents and integrated clinical datasets to uncover proliferation and resistance-associated genes with prognostic potential. Drug response similarity networks revealed both shared and unique mechanisms, highlighting key pathways such as autophagy, apoptosis, and Wnt signaling, and notable resistance-associated genes including BCL2, POLD2, and TRADD. In particular, we proposed a synergistic combination of the BCL2 family inhibitor ABT-263 (Navitoclax&#xae;) and the DNA analog TAS-102 (Lonsurf&#xae;), which revealed that lysosomal modulation is a key mechanism driving DNA analog resistance. This combination therapy selectively enhanced cytotoxicity in colorectal and pancreatic cancer cells in vitro, and demonstrated therapeutic benefit in vivo in both cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models. Together, these findings establish BOGO as a powerful gene overexpression perturbation platform for systematically identifying chemoresistance and chemosensitization drivers, and for discovering rational combination therapies. Its scalability and reproducibility position BOGO as a broadly applicable tool for functional genomics and therapeutic discovery beyond cancer resistance.

Journal Article↗
PubMed1993

Incidence of myocardial infarction and mortality from specific causes among bus drivers in Sweden.

Previous studies have indicated that urban bus drivers have an increased risk of coronary heart disease. In the present investigation two separate studies were carried out. In the first study the mortality from myocardial infarction (MI), as well as from other causes for all male bus drivers in Sweden (9446), was investigated and compared to those of other employed men over a 15-year period. A 50% increase in mortality from MI was observed among drivers in Stockholm and Göteborg and Bohus counties, the two counties where the two largest cities in Sweden are situated. No increased mortality from lung cancer, any cancer (all sites combined), or from all causes combined was observed for these drivers. For bus drivers in the predominantly rural areas no excess mortality from MI, or any other cause, was observed. In the second study the incidence of MI among male bus drivers, as compared with other employed men, was studied in five Swedish counties by case referent methods. An increased incidence of first events of MI, (relative risk = 1.6, 95% confidence interval (CI) 1.1-1.9) was observed for bus drivers in Stockholm county. According to our results, urban bus drivers thus have an increased risk of developing MI. The findings also suggest that factors in the work environment of urban bus drivers may contribute to this increased risk. Factors of possible importance are job strain, irregular working hours, a sedentary job, automobile exhaust fumes, and noise.

Automobile Driving↗
PubMedDate not supplied

Pregnancy termination in relation to risk of breast cancer.

OBJECTIVE: To evaluate the association between pregnancy terminations and risk of breast cancer. DESIGN AND SETTING: Population-based case-control study in Wisconsin, Massachusetts, Maine, and New Hampshire. STUDY PARTICIPANTS: Cases were women younger than 75 years with a new diagnosis of breast cancer (n = 6888), identified from statewide tumor registries. Controls younger than 65 years (n = 9529) were randomly selected from lists of licensed drivers, or for older subjects, from lists of Medicare beneficiaries. EXPOSURES AND OUTCOMES: Breast cancer risk in relation to spontaneous or induced abortions. RESULTS: After adjustment for parity, age at first birth, and other risk factors, pregnancy termination (induced or spontaneous) was associated with a relative risk (RR) of breast cancer of 1.12 (95% confidence interval [CI], 1.04 to 1.21), compared with the risk among women who had never had a termination. Induced terminations were associated with a RR of 1.23 (95% CI, 1.00 to 1.51), which was somewhat greater than the risk associated with spontaneous terminations (RR, 1.11; 95% CI, 1.02 to 1.20). The association with induced abortions was stronger for those performed before legalization of abortion in 1973 (RR, 1.35; 95% CI, 1.01 to 1.80) than after this time (RR, 1.12; 95% CI, 0.84 to 1.49), suggesting a bias in reporting this sensitive procedure. CONCLUSIONS: A weak positive association was observed between abortion--whether induced or spontaneous--and risk of breast cancer. The increase in risk of breast cancer was somewhat greater among women with a history of induced terminations. However, this association may be due to reporting bias and was not significantly different than the slight risk for spontaneous terminations.

Abortion, Induced↗
PubMed1992

Epidemiology of bladder cancer.

Approximately 49,000 persons in the United States develop bladder cancer each year, and about 9700 die of it. White men face a lifetime risk of almost 3%; white women and black men face a risk of about 1%, and black women, about 0.5%. Cigarette smoking is accepted widely as a cause of bladder cancer. Smoking accounts for about half of bladder cancer diagnosed among men and about one third of that among women. Moderate to heavy smokers typically show a two to five fold risk of bladder cancer, compared with persons who never smoked. When cigarette smokers quit smoking, their bladder cancer risk falls measurably within 2 to 4 years, but probably does not continue to decline with increasing years since quitting and does not appear to return to the baseline level of nonsmokers. Occupational exposure to certain aromatic amines causes human bladder cancer. Clear evidence of bladder cancer risk also is apparent for a small number of occupational groups: dye workers, rubber workers, leather workers, painters, truck drivers, and aluminum workers. Many other occupational groups have been reported to have increased bladder cancer risk, but evidence for these is not as strong. Coffee drinking has been studied extensively as a potential risk factor, but the inconsistency of the observed associations suggests that the relationship is either quite weak, noncausal, or dependent in a complex way on unmeasured factors. Artificial sweeteners confer little or no excess bladder cancer risk. Alcohol consumption apparently does not affect risk either. Consumption of fruits, vegetables, and foods high in vitamin A have been suggested as possible protective factors; consumption of high-fat foods, pork, and beef have been suggested as possible risk factors. Further epidemiologic research is needed to elucidate the role of diet in human bladder carcinogenesis. Less common risk factors for bladder cancer include ionizing radiation, cyclophosphamide use, and abuse of phenacetin-containing analgesics. Schistosomiasis infection may contribute substantially to the bladder cancer burden in Egypt and elsewhere, though not in the United States.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed2004

Diet and alcohol consumption in relation to p53 mutations in breast tumors.

There is evidence linking alcohol consumption to p53 mutations in tumors, considerable evidence linking alcohol consumption with risk of breast cancer and some evidence that alcohol and folate consumption interact to affect risk. Further, while there is some indication that oxidation may play a role in breast cancer etiology, there has been little examination of an association of oxidative stress with p53 mutations. We examined several dietary components related to one-carbon metabolism and antioxidants to determine if these factors were related to the prevalence of p53 mutations in breast tumors. We conducted a case-control study of primary, histologically confirmed breast cancer in western New York. Controls <65 were selected from drivers license lists; those > or =65 were selected from Health Care Finance Administration lists. p53 mutations in archived tumor blocks were identified in exons 2-11 and flanking intron sequences. Usual dietary intake was assessed by interview regarding intake in the previous 2 years; alcohol consumption was queried for 2, 10 and 20 years in the past. Our data were consistent with increased likelihood of tumors with p53 mutations for premenopausal breast cancer with increased alcohol intake 10 or 20 years previous; for intake of 16 or more drinks per month in the period 20 years before the interview compared with non-drinkers, the OR was 5.25, 95% CI 1.48-18.58. For postmenopausal women, there was increased likelihood of tumors with p53 mutations among women with higher folate. Antioxidant nutrients were not differentially related to p53 mutations. These results indicate that there may be heterogeneity in breast tumors, as indicated by differences in associations for those with or without p53 mutations, and that causal pathways for these nutrients may vary for pre- and postmenopausal women. For premenopausal women, alcohol consumption in the past was associated with p53 mutations.

Adult↗
PubMed2003

Occupations with increased risk of pancreatic cancer in the Swedish population.

AIMS: To identify occupations with increased risk of pancreatic cancer in the Swedish population gainfully employed in 1970 over the period 1971-89. METHODS: The base population was made up of Swedish men (1 779 646) and Swedish women (1 101 669) gainfully employed at the time of the 1970 census and were still alive and over age 24 on 1 January 1971. Information was drawn from two data sets: the Swedish cancer environment register and a background population register. After 19 years of follow up, 4420 men and 2143 women were diagnosed with histologically confirmed incident pancreatic adenocarcinoma. Log linear Poisson models were fitted, allowing for geographical area and town size. Risk estimators were also calculated for workers reporting the same occupation in 1960 and 1970. RESULTS: Among women, a statistically significant risk excess of pancreatic cancer was observed for "educational methods advisors", "librarian, archivist, curator", "motor vehicle driver", "typographer, lithographer", "purser, steward, stewardess", "other housekeeping and related workers", and the groups of occupations of "electrical, electronic, and related" and "glass, pottery, and tile workers". Men showed a higher incidence of pancreatic cancer among "technical assistants", "travelling agents", "other metal processing workers", "baker and pastry cook", "docker and freight handler", and "waiters". CONCLUSIONS: This study does not indicate that occupational factors play an important role in the aetiology of pancreatic cancer in Sweden. Few occupations were at increased risk of pancreatic cancer in both men and women, and the associations observed are in accordance with some previous studies from Western countries.

Adult↗
PubMed1987

Sequential histological studies of rat oesophagus during the rapid initiation of cancer by repeated injection of N-methyl-N-benzylnitrosamine.

The sequence of histological changes leading to oesophageal cancer in animals after treatment with various nitrosamines has been studied previously using systems which induced cancer relatively slowly. The more potent carcinogen, N-methyl-N-benzylnitrosamine (MBzN), has been employed to induce cancer in a very much shorter time in experiments designed to detect factors which may potentiate oesophageal cancer. MBzN injected twice weekly for 4 weeks induces papillomas by 4 weeks and carcinomas by 9 weeks. The histological events occurring during the 4-week treatment period have been studied. Initially there was an increase in mitosis. After the second injection, destruction of basal cells occurred, with their complete disappearance from stretches of the epithelium, accompanied by a massive influx of inflammatory cells, and disruption of the normal architecture of the oesophageal epithelium. After 1-2 weeks the numbers of inflammatory cells decreased, concurrently with basal cell hyperplasia and dysplasia, where replicating basal cells penetrated down into the submucosa and upwards towards the lumen. Thickening of the spinous and granular layers of the epithelium and hyperkeratosis were evident, and after 30 days a macroscopically visible papilloma was present. It therefore appears that resistance develops to the toxic inhibitory effect of the carcinogen, and this allows the abnormal replication of basal cells to occur even in the continued presence of the carcinogen. The biochemical processes underlying this development of resistance are being studied, and the effects of possible potentiating factors on the sequence of events occurring during carcinogenesis are being used to test for dietary factors which may enhance oesophageal cancer.

Animals↗
PubMed2001

Fracture history and risk of breast and endometrial cancer.

Fractures in postmenopausal women may serve as a surrogate measure of bone density, reflecting long-term lower estrogen levels, and lower estrogen levels appear to be inversely associated with breast and endometrial cancer. Breast cancer cases aged 50-79 years (n = 5,559) and endometrial cancer cases aged 40-79 years (n = 739) were enrolled in a US case-control study in 1992-1994 to evaluate the relation between fractures and risk of breast and endometrial cancer. Controls for the breast cancer analysis (n = 5,829) and the endometrial cancer analysis (n = 2,334) were randomly selected from population lists (driver's license and Medicare files). Information on fracture history and other risk factors was obtained by telephone interview. Compared with women without a fracture in the past 5 years, the odds ratios for women with a history of fracture were 0.80 (95% confidence interval (CI): 0.68, 0.94) for breast cancer and 0.59 (95% CI: 0.40, 0.89) for endometrial cancer. Height loss (> or =2.5 cm) and recent fracture history were associated with the lowest risk of breast cancer (odds ratio = 0.62, 95% CI: 0.46, 0.83) and endometrial cancer (odds ratio = 0.15, 95% CI: 0.05, 0.43). These data suggest that the endogenous hormonal factors associated with increased fracture risk are also related to decreased breast cancer risk and, more strongly, to endometrial cancer risk.

Adult↗
PubMed1997

Physical activity in usual occupation and risk of breast cancer (United States).

We have used data from a large population-based case-control study in the United States to evaluate the effect of occupational physical activity on breast cancer risk. Women diagnosed with breast cancer identified from four state cancer registries, and controls randomly selected from lists of licensed drivers or Medicare beneficiaries, were interviewed by telephone for information on usual occupation and other factors. We classified usual occupation into one of four categories of physical activity. After excluding subjects for whom a strength rating could not be assigned, we had a final sample size of 4,863 cases and 6,783 controls. Using conditional logistic regression models, we calculated adjusted odds ratios (OR) and 95 percent confidence intervals (CI) for occupations having light, medium, and heavy activity compared with sedentary ones. Women with heavy-activity occupations had a lower risk of breast cancer than women with sedentary jobs (OR = 0.82, CI = 0.63-1.08), as did women with jobs with medium activity (OR = 0.86, CI = 0.77-0.97) or light activity (OR = 0.92, CI = 0.84-1.01). There was a significant decreasing trend in the ORs from sedentary to heavy work (P = 0.007). Although limited by exposure misclassification, these data are consistent with the hypothesis that physical activity reduces the risk of breast cancer.

Adult↗
PubMed1993

Race and sex differences in associations of vegetables, fruits, and carotenoids with lung cancer risk in New Jersey (United States).

We used data from a case-control study conducted in New Jersey between 1980 and 1983 to evaluate race and sex differences in associations of vegetable, fruit, and carotenoid consumption with lung cancer. Cases included 736 White males, 860 White females, 269 Black males, and 86 Black females with incident, histologically confirmed, primary cancer of the trachea, bronchus, or lung. Controls were identified through drivers' license and Health Care Financing Administration files and included 548 White males, 473 White females, 170 Black males, and 47 Black females. Usual intakes of vegetables (predominantly yellow/green) and fruit (predominantly yellow/orange) as well as other food sources of carotenoids were ascertained by a food frequency questionnaire. White females showed significant inverse associations of lung cancer with vegetables, fruit, and carotenoids. White males showed nonsignificant inverse associations with vegetables and carotenoids, and Black females just with vegetables. No inverse associations were found for Black males. Vegetable consumption was associated with risk of all histologic types of lung cancer, but the pattern of increasing risk with decreasing intake was limited to smokers. We infer that consumption of yellow/green vegetables and carotenoids may confer protection from lung cancer to White male and White female smokers. Further studies are needed to clarify the effect in Blacks.

Black or African American↗
PubMed2006

Recurrent KRAS codon 146 mutations in human colorectal cancer.

An activating point mutation in codon 12 of the HRAS gene was the first somatic point mutation identified in a human cancer and established the role of somatic mutations as the common driver of oncogenesis. Since then, there have been over 11,000 mutations in the three RAS (HRAS, KRAS and NRAS) genes in codons 12, 13 and 61 reported in the literature. We report here the identification of recurrent somatic missense mutations at alanine 146, a highly conserved residue in the guanine nucleotide binding domain. In two independent series of colorectal cancers from Hong Kong and the United States we detected KRAS A146 mutations in 7/126 and 2/94 cases, respectively, giving a combined frequency of 4%. We also detected KRAS A146 mutations in 2/40 (5%) colorectal cell lines, including the NCI-60 colorectal cancer line HCC2998. Codon 146 mutations thus are likely to make an equal or greater contribution to colorectal cancer than codon 61 mutations (4.2% in our combined series, 1% in the literature). Lung adenocarcinomas and large cell carcinomas did not show codon 146 mutations. We did, however, identify a KRAS A146 mutation in the ML-2 acute myeloid leukemia cell line and an NRAS A146 mutation in the NALM-6 B-cell acute lymphoblastic leukemia line, suggesting that the contribution of codon 146 mutations is not entirely restricted to colorectal cancers or to KRAS.

Adenocarcinoma↗