vitamin-k-1 and Neoplasms

Cancer incidences are growing rapidly and causing millions of deaths globally. Cancer treatment is one of the most exigent challenges. Drug resistance is a natural phenomenon and is considered one of the major obstacles in the successful treatment of cancer by chemotherapy. Combination therapy by the amalgamation of various anticancer drugs has suggested modulating tumor response by targeting various signaling pathways in a synergistic or additive manner. Vitamin K is an essential nutrient and has recently been investigated as a potential anticancer agent. The combination of vitamin K analogs, such as vitamins K1, K2, K3, and K5, with other chemotherapeutic drugs have demonstrated a safe, cost-effective, and most efficient way to overcome drug resistance and improved the outcomes of prevailing chemotherapy. Published reports have shown that vitamin K in combination therapy improved the efficacy of clinical drugs by promoting apoptosis and cell cycle arrest and overcoming drug resistance by inhibiting P-glycoprotein. In this review, we discuss the mechanism, cellular targets, and possible ways to develop vitamin K subtypes into effective cancer chemosensitizers. Finally, this review will provide a scientific basis for exploiting vitamin K as a potential agent to improve the efficacy of chemotherapeutic drugs.

Topics: Antineoplastic Agents; Humans; Neoplasms; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K 3

The main function of vitamin K in the human organism is its activity in the blood clotting cascade. Epidemiological studies suggest that reduced intake of vitamin K may contribute to an increased risk of geriatric diseases such as atherosclerosis, dementia, osteoporosis, and osteoarthritis. A growing number of studies also indicate that vitamin K may be involved not only in preventing the development of certain cancers but it may also support classical cancer chemotherapy. This review article summarizes the results of studies on the anticancer effects of vitamin K on selected female malignancies, i.e., breast, cervical, and ovarian cancer, published over the past 20 years. The promising effects of vitamin K on cancer cells observed so far indicate its great potential, but also the need for expansion of our knowledge in this area by conducting extensive research, including clinical trials.

Topics: Aged; Blood Coagulation; Female; Humans; Neoplasms; Osteoporosis; Ovarian Neoplasms; Vitamin K; Vitamin K 1; Vitamin K 2

Phylloquinone (vitamin K1) and menaquinones (vitamin K2 family) are essential for post-translational γ-carboxylation of a small number of proteins, including clotting factors. These modified proteins have now been implicated in diverse physiological and pathological processes including cancer. Vitamin K intake has been inversely associated with cancer incidence and mortality in observational studies. Newly discovered functions of vitamin K in cancer cells include activation of the steroid and xenobiotic receptor (SXR) and regulation of oxidative stress, apoptosis, and autophagy. We provide an update of vitamin K biology, non-canonical mechanisms of vitamin K actions, the potential functions of vitamin K-dependent proteins in cancer, and observational trials on vitamin K intake and cancer.

Topics: Biology; Humans; Neoplasms; Pregnane X Receptor; Proteins; Vitamin K; Vitamin K 1; Vitamin K 2

The assessment of the vitamin K status and its effects on clinical outcomes in kidney transplantation (KT) patients has sparked interest, but it is still largely unfulfilled. In part, this is due to difficulties in laboratory measurements of vitamin K, especially K2 vitamers. Vitamin K status is currently best assessed by measuring undercarboxylated vitamin-K-dependent proteins. The relative contribution of vitamin K1 and K2 to the health status of the general population and CKD (chronic kidney disease) patients, including KT patients, is also poorly studied. Through a complete and first review of the existing literature, we summarize the current knowledge of vitamin K pathophysiology and its potential role in preventing KT complications and improving organ survival. A specific focus is placed on cardiovascular complications, bone fractures, and the relationship between vitamin K and cancer. Vitamin K deficiency could determine adverse outcomes, and KT patients should be better studied for vitamin K assessment and modalities of effective therapeutic approaches.

Topics: Cardiovascular Diseases; Fractures, Bone; Humans; Kidney Transplantation; Neoplasms; Nutritional Status; Postoperative Complications; Preoperative Period; Renal Insufficiency, Chronic; Treatment Outcome; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency

Topics: Aging; Anti-Bacterial Agents; Biomarkers; Chromatography, High Pressure Liquid; Electrochemistry; Humans; Kidney Diseases; Neoplasms; Protein Precursors; Prothrombin; Reference Values; Risk Factors; Specimen Handling; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency

Vitamin K, an essential nutrient often associated with the clotting cascade, has been the focus of considerable research demonstrating an anticancer potential. Much of this research has focused on vitamin K3, although vitamins K2 and K1 have also been shown to have anticancer effects. Early studies of vitamin K3 employed an oxidative model to explain the anticancer effects seen in both in vitro and in vivo studies; however, this model does not adequately address the action of vitamins K1 and K2. Recent research has demonstrated the anticancer action of vitamin K may act at the level of tyrosine kinases and phosphatases, modulating various transcription factors such as Myc and Fos. Tyrosine kinases associated with cyclins have also been shown to be affected by vitamin K, which can lead to cell cycle arrest and cell death.

Topics: Animals; Anticarcinogenic Agents; Cell Cycle; Humans; Mice; Neoplasms; Rats; Transcription Factors; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K 3

The microsomal mixed function oxidase system metabolizes xenobiotics (Phase I) to products that, if not activated and conjugated for excretion (Phase II), are capable of forming conjugates with cellular macromolecules, including DNA, resulting in toxic, mutagenic, or carcinogenic events. Benzo(a)pyrene (BP), a polycyclic aromatic hydrocarbon, is a model carcinogen for this system. Vitamin K1 (phylloquinone) is a regulator of BP metabolism. These studies demonstrate that K1 is capable of increasing Phase I metabolism and decreasing glutathione transferase activity (Phase II) in chick embryo liver; that deprivation of K1 reduces BP/DNA adducts in mouse liver and reduces tumor formation in mice given intraperitoneal BP; and that K1 supplementation increases BP induced tumor formation in mice. However, epidemiologic studies indicate that children of mothers who smoke during pregnancy may not be at increased risk of cancer. It is known that the placentas from these pregnancies exhibit markedly increased levels of arylhydrocarbon hydroxylase induced by the polycyclic aromatic hydrocarbons in tobacco smoke, but there is no corresponding increase in this enzyme activity in the fetus in such pregnancies. We suggest that the low vitamin K level is a secondary protective mechanism for xenobiotics, such as BP, that may escape the primary placental screen. The recently described role of vitamin K-dependent Gla protein as ligands for receptor tyrosine kinases, also establishes K as a link in cell growth and transformation. It is proposed that the small total body pool of K1 in the adult, which is sufficient only to meet continuing needs, and the even smaller pool in the fetus are protective. This protective effect of low K1 levels is particularly important in the presence of the high mitotic rates and rapid cell turnover in the avian embryo and mammalian fetus.

Topics: 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; Adult; Animals; Biotransformation; Carcinogens; Chick Embryo; Cocarcinogenesis; DNA Adducts; Female; Fetal Diseases; Fetus; Humans; Infant, Newborn; Liver; Maternal Exposure; Maternal-Fetal Exchange; Mice; Mice, Inbred ICR; Microsomes, Liver; Mixed Function Oxygenases; Neoplasms; Neoplasms, Experimental; Placenta; Pregnancy; Prenatal Exposure Delayed Effects; Smoking; Vitamin K; Vitamin K 1; Vitamin K Deficiency; Warfarin; Xenobiotics

Topics: Age Factors; Europe; Hemostasis; Humans; Incidence; Infant; Infant, Newborn; Japan; Neoplasms; Practice Guidelines as Topic; Vitamin K; Vitamin K 1; Vitamin K Deficiency Bleeding

Topics: Antibiotics, Antineoplastic; Antineoplastic Agents; Chloroquine; Cyclophosphamide; Cytarabine; Drug Synergism; Fluorouracil; Humans; Japan; Leukemia; Lymphoma; Mercaptopurine; Mitomycins; Neoplasms; Podophyllin; Prednisolone; Thiotepa; Vincristine; Vitamin K 1

Vitamin K has been related to cardiovascular disease and cancer risk. However, data on total mortality are scarce. The aim of the present study was to assess the association between the dietary intake of different types of vitamin K and mortality in a Mediterranean population at high cardiovascular disease risk. A prospective cohort analysis was conducted in 7216 participants from the PREDIMED (Prevención con Dieta Mediterránea) study (median follow-up of 4.8 y). Energy and nutrient intakes were evaluated using a validated 137-item food frequency questionnaire. Dietary vitamin K intake was calculated annually using the USDA food composition database and other published sources. Deaths were ascertained by an end-point adjudication committee unaware of the dietary habits of participants after they had reviewed medical records and linked up to the National Death Index. Cox proportional hazard models were fitted to assess the RR of mortality. Energy-adjusted baseline dietary phylloquinone intake was inversely associated with a significantly reduced risk of cancer and all-cause mortality after controlling for potential confounders (HR: 0.54; 95% CI: 0.30, 0.96; and HR: 0.64; 95% CI: 0.45, 0.90, respectively). In longitudinal assessments, individuals who increased their intake of phylloquinone or menaquinone during follow-up had a lower risk of cancer (HR: 0.64; 95% CI: 0.43, 0.95; and HR: 0.41; 95% CI: 0.26, 0.64, respectively) and all-cause mortality (HR: 0.57; 95% CI: 0.44, 0.73; and HR: 0.55; 95% CI: 0.42, 0.73, respectively) than individuals who decreased or did not change their intake. Also, individuals who increased their intake of dietary phylloquinone had a lower risk of cardiovascular mortality risk (HR: 0.52; 95% CI: 0.31, 0.86). However, no association between changes in menaquinone intake and cardiovascular mortality was observed (HR: 0.76; 95% CI: 0.44, 1.29). An increase in dietary intake of vitamin K is associated with a reduced risk of cardiovascular, cancer, or all-cause mortality in a Mediterranean population at high cardiovascular disease risk. This trial was registered at http://www.controlled-trials.com as ISRCTN35739639.

Topics: Aged; Aged, 80 and over; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diet, Mediterranean; Female; Follow-Up Studies; Humans; Incidence; Male; Mediterranean Region; Middle Aged; Neoplasms; Plant Oils; Proportional Hazards Models; Prospective Studies; Risk Factors; Vegetables; Vitamin K; Vitamin K 1; Vitamin K 2

In 34 cancer patients with 40 neutropenic febrile episodes requiring broad-spectrum antimicrobial therapy, detailed dietary assessments revealed that deficient and severely deficient phylloquinone intakes (less than or equal to 70 and less than or equal to 25 micrograms/d) were identified during 88% and 38% of all days recorded, respectively. Serum phylloquinone levels and serial prothrombin times (PT) drawn in a similar group of 32 patients revealed that an elevated PT (greater than or equal to 2 s beyond control) was significantly associated (p less than 0.01) with a serum phylloquinone level of less than 4.4 nmol/L. Patients on antimicrobial regimens that suppressed menaquinone-producing intestinal microflora and that contained an N-methylthiotetrazole (NMTT) moiety had an elevated PT significantly more often than did patients receiving antimicrobial agents that preserved the microflora and contained no NMTT moiety (3 of 10 vs 10 of 11, respectively; p = 0.02 Fisher's exact). These data suggest that these patients have a profound deficiency of oral vitamin K intake that may be further augmented by antimicrobial therapy.

Topics: Agranulocytosis; Anti-Bacterial Agents; Diet; Fever; Humans; Hypoprothrombinemias; Intestines; Neoplasms; Neutropenia; Prothrombin Time; Vitamin K; Vitamin K 1; Vitamin K Deficiency

Observational studies have reported lower risks of type 2 diabetes with higher vitamin K1 intake, but these studies overlook effect modification due to known diabetes risk factors.. To identify subgroups that might benefit from vitamin K1 intake, we examined associations between vitamin K1 intake and incident diabetes overall and in subpopulations at risk of diabetes.. Participants from the prospective cohort, the Danish Diet, Cancer, and Health Study, with no history of diabetes were followed up for diabetes incidence. The association between intake of vitamin K1, estimated from a food frequency questionnaire completed at baseline, and incident diabetes was determined using multivariable-adjusted Cox proportional-hazards models.. In 54 787 Danish residents with a median (interquartile range) age of 56 (52-60) years at baseline, 6700 individuals were diagnosed with diabetes during 20.8 (17.3-21.6) years of follow-up. Vitamin K1 intake was inversely and linearly associated with incident diabetes (P < .0001). Compared to participants with the lowest vitamin K1 intake (median:57 µg/d), participants with the highest intakes (median:191 µg/d) had a 31% lower risk of diabetes (HR; 95% CI, 0.69; 0.64-0.74) after multivariable adjustments. The inverse association between vitamin K1 intake and incident diabetes was present in all subgroups (namely, men and women, ever and never smokers, low and high physical activity groups, and in participants who were normal to overweight and obese), with differences in absolute risk between subgroups.. Higher intake of foods rich in vitamin K1 was associated with a lower risk of diabetes. If the associations observed are causal, our results indicate that more cases of diabetes would be prevented in subgroups at higher risk (men, smokers, participants with obesity, and those with low physical activity).

Topics: Denmark; Diabetes Mellitus, Type 2; Diet; Female; Humans; Male; Middle Aged; Neoplasms; Obesity; Prospective Studies; Risk Factors; Vitamin K 1; Vitamin K 2

Skin toxicity in patients receiving novel therapeutic cancer agents has become a very important marker in determining drug activity, but it can also severely impact their quality of life. About half of the patients receiving this type of oncologic treatment will develop cutaneous reactions, that is why adequate understanding and management of these side effects is very important for drug adherence and patients' quality of life.. We conducted a prospective study of consecutive patients who received oncologic treatment in our institution and presented with dermatologic side effects. The severity of skin toxicity was assessed using the DLQI score and patients were prospectively followed to evaluate response to therapy. Univariate analysis of factors influencing the impact of skin toxicity on patient QOL was conducted.. 52 patients were enrolled in the study. Patients who developed grade 3 and 4 skin toxicity had a higher DLQI score, with a greater impact on quality of life, but with better clinical outcome at 3 months follow-up, based on RECIST. Patients with moderate or severe cutaneous AE were more likely to achieve complete or partial response to therapy than those with mild AE (16/33 vs. 3/19, p = 0.035). Interestingly, female patients had a significantly poorer quality of life than male patients as assessed by the DLQI score (7.28 ± 7 vs. 3.7 ± 3.6, p = 0.038).. Cutaneous side effects are often encountered in cancer patients and their severity can be a surrogate marker for a positive clinical tumor response to therapy.

Topics: Adrenal Cortex Hormones; Aged; Anti-Bacterial Agents; Antineoplastic Agents; Drug Eruptions; ErbB Receptors; Exanthema; Female; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Protein-Tyrosine Kinases; Quality of Life; Severity of Illness Index; TOR Serine-Threonine Kinases; Vitamin K 1; Vitamins

Vitamin K has been associated with various health outcomes, including non-fatal cardiovascular diseases (CVD) and cancer. However, little is known about the association between vitamin K intake and all-cause and cause specific mortality. This study aims to investigate the association between vitamin K intake and all-cause and cause-specific mortality.. This prospective cohort study included 33,289 participants from the EPIC-NL cohort, aged 20-70 years at baseline and recruited between 1993 and 1997. Dietary intake was assessed at baseline with a validated food frequency questionnaire and intakes of phylloquinone, and total, short chain and long chain menaquinones were calculated. Information on vital status and causes of death was obtained through linkage to several registries. The association between the different forms of vitamin K intake and mortality was assessed with Cox proportional hazards, adjusted for risk factors for chronic diseases and nutrient intake.. During a mean follow-up of 16.8 years, 2863 deaths occurred, including 625 from CVD (256 from coronary heart disease (CHD)), 1346 from cancer and 892 from other causes. After multivariable adjustment, phylloquinone and menaquinones were not associated with all-cause mortality with hazard ratios for the upper vs. the lowest quartile of intake of 1.04 (0.92;1.17) and 0.94 (0.82;1.07) respectively. Neither phylloquinone intake nor menaquinone intake was associated with risk of CVD mortality. Higher intake of long chain menaquinones was borderline significantly associated (p. Vitamin K intake was not associated with all-cause mortality, cancer mortality and mortality from other causes.

Topics: Adult; Aged; Body Mass Index; Cardiovascular Diseases; Chronic Disease; Fatty Acids; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Mortality; Neoplasms; Nutrition Assessment; Prevalence; Proportional Hazards Models; Prospective Studies; Risk Factors; Surveys and Questionnaires; Vitamin K; Vitamin K 1; Vitamin K 2; Young Adult

Anticarcinogenic activities of vitamin K have been observed in animal and cell studies.. On the basis of the growth inhibitory effects of vitamin K as observed in a variety of cancer cell lines, we hypothesized that dietary intake of phylloquinone (vitamin K(1)) and menaquinones (vitamin K(2)) may be associated with overall cancer incidence and mortality.. In the prospective EPIC-Heidelberg (European Prospective Investigation into Cancer and Nutrition-Heidelberg) cohort study, 24,340 participants aged 35-64 y and free of cancer at enrollment (1994-1998) were actively followed up for cancer incidence and mortality through 2008. Dietary vitamin K intake was estimated from food-frequency questionnaires completed at baseline by using HPLC-based food-composition data. Multivariate-adjusted hazard ratios (HRs) and 95% CIs were estimated by using Cox proportional hazards models.. During a median follow-up time of >10 y, 1755 incident cancer cases occurred, of which 458 were fatal. Dietary intake of menaquinones was nonsignificantly inversely associated with overall cancer incidence (HR for the highest compared with the lowest quartile: 0.86; 95% CI: 0.73, 1.01; P for trend = 0.08), and the association was stronger for cancer mortality (HR: 0.72; 95% CI: 0.53, 0.98; P for trend = 0.03). Cancer risk reduction with increasing intake of menaquinones was more pronounced in men than in women, mainly driven by significant inverse associations with prostate (P for trend = 0.03) and lung (P for trend = 0.002) cancer. We found no association with phylloquinone intake.. These findings suggest that dietary intake of menaquinones, which is highly determined by the consumption of cheese, is associated with a reduced risk of incident and fatal cancer.

Topics: Adult; Cell Division; Cheese; Diet; Educational Status; Exercise; Female; Follow-Up Studies; Germany; Humans; Male; Middle Aged; Neoplasms; Postmenopause; Risk Reduction Behavior; Smoking; Vitamin K; Vitamin K 1; Vitamin K 2

Many patients with advanced cancer are malnourished. Anorexia is common, as is the use of chemotherapy, which may cause nausea and poor appetite. Ten per cent of these patients experience haemorrhagic events.. Since vitamin K deficiency (VKD) causes bleeding, to establish the prevalence of VKD in patients with advanced cancer receiving palliative care.. Serum concentrations of vitamin K(1) and undercarboxylated factor II (PIVKA-II) were determined in 46 (17 male/29 female) inpatients aged 26-85 (mean 58) years. INR and liver function tests (bilirubin, ALT, GGT and ALP) were also performed.. Vitamin K(1) was below the lower limit of the reference range (0.33 nmol/l) in 22% of patients. 78% of patients had some degree of functional VKD indicated by raised (>0.2 AU/ml) PIVKA-II. Six patients (13%) had a prolonged INR, all of whom had raised PIVKA-II and GGT; 4 also had vitamin K(1) <0.33 nmol/l. Three patients (6.5%) had clinically significant VKD characterised by INR >1.5, PIVKA-II >10 AU/ml, and undetectable vitamin K(1).. Patients with advanced cancer are prone to VKD which, while usually subclinical, may develop to a clinically relevant prolongation of the INR. Serum measurements of vitamin K(1) and PIVKA-II can be used to detect VKD and monitor vitamin K status before an increased risk of bleeding develops.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Female; Hemostatic Disorders; Humans; International Normalized Ratio; Male; Middle Aged; Neoplasms; Palliative Care; Protein Precursors; Prothrombin; Vitamin K 1; Vitamin K Deficiency

Clinical cases of capecitabine and other fluorouracil-based chemotherapies potentiating the effects of coumarin derivatives have been reported. This study assessed the influence of capecitabine on the pharmacokinetics (PK) and pharmacodynamics (PD) of warfarin.. Four patients with advanced/metastatic cancer completed the study, receiving a single oral dose of 20 mg warfarin before the start of standard capecitabine treatment (day 1), and again during the third cycle of capecitabine (day 61). PK parameters of warfarin and capecitabine and PD parameters of warfarin were assessed on days 1 and 61.. During capecitabine treatment, the area under the plasma concentration time curve from 0 to infinity (AUC(0-infinity)) of S-warfarin increased by 57% (90% CI, 32% to 88%) with a 51% prolongation of the elimination half-life (t(1/2); 90% CI, 32% to 74%). Exposure to R-warfarin was not significantly affected. Plasma concentrations of capecitabine and its metabolites were not influenced by warfarin. During capecitabine treatment, the effect of warfarin on the baseline corrected AUC of the International Normalized Ratio (INR) increased by 2.8 times (90% CI, 1.33 to 5.70), with the maximum observed INR value almost doubling. Because of the administration of vitamin K to some patients with elevated INRs, these figures are likely to underestimate the true PD effect. Mean baseline factor VII levels dropped while on capecitabine therapy, potentially contributing to the observed PD interaction, though this effect did not reach statistical significance.. There is a significant pharmacokinetic interaction between capecitabine and S-warfarin, resulting in exaggerated anticoagulant activity. Patients receiving warfarin anticoagulant therapy concomitantly with capecitabine should have their INR closely monitored and warfarin doses adjusted accordingly.

Topics: Adult; Anticoagulants; Antimetabolites, Antineoplastic; Capecitabine; Deoxycytidine; Drug Synergism; Factor VII; Fluorouracil; Half-Life; Humans; Middle Aged; Neoplasms; Prothrombin Time; Vitamin K 1; Warfarin

An elevated international normalized ratio (INR) increases the risk for major hemorrhage during warfarin therapy. Optimal management of patients with asymptomatic elevations in INR is hampered by the lack of understanding of the time course of INR decay after cessation of warfarin therapy.. To identify predictors of the rate of INR normalization after excessive anticoagulation.. Retrospective cohort study.. Outpatient anticoagulant therapy unit.. Outpatients with an INR greater than 6.0 were identified from August 1993 to September 1998. Patients in whom two doses of warfarin were withheld and a follow-up INR was obtained on the second calendar day were enrolled. No patient received vitamin K(1).. The INR was measured 2 days after an INR greater than 6.0 was recorded.. Of 633 study patients with an initial INR greater than 6.0, 232 (37%) still had an INR of 4.0 or greater after two doses of warfarin were withheld. Patients who required larger weekly maintenance doses of warfarin were less likely to have an INR of 4.0 or greater on day 2 (adjusted odds ratio per 10 mg of warfarin, 0.87 [95% CI, 0.79 to 0.97]). Other risk factors for having an INR of 4.0 or greater on day 2 included age (odds ratio per decade of life, 1.18 [CI, 1.01 to 1.38]), index INR (odds ratio per unit, 1.25 [CI, 1.14 to 1.37]), decompensated congestive heart failure (odds ratio, 2.79 [CI, 1.30 to 5.98]), and active cancer (odds ratio, 2.48 [CI, 1.11 to 5.57]).. Steady-state warfarin dose, advanced age, and extreme elevation in INR are risk factors for prolonged delay in return of the INR to within the therapeutic range. Decompensated congestive heart failure and active cancer greatly increase this risk.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Antifibrinolytic Agents; Cohort Studies; Female; Half-Life; Heart Failure; Hemorrhage; Humans; International Normalized Ratio; Logistic Models; Male; Neoplasms; Retrospective Studies; Risk Factors; Time Factors; Vitamin K 1; Warfarin

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Antifibrinolytic Agents; Cohort Studies; Female; Heart Failure; Hemorrhage; Humans; International Normalized Ratio; Male; Neoplasms; Retrospective Studies; Risk Factors; Time Factors; Vitamin K 1; Warfarin

To assess unexpected associations between childhood cancer and pethidine given in labour and the neonatal administration of vitamin K that had emerged in a study performed in the 1970 national birth cohort.. 195 children with cancer diagnosed in 1971-March 1991 and born in the two major Bristol maternity hospitals in 1965-87 were compared with 558 controls identified from the delivery books for the use of pethidine during labour and administration of vitamin K.. Odds ratios for cancer in the presence of administration of pethidine or of intramuscular vitamin K. Both logistic regression and Mantel-Haenszel techniques were used for statistical analyses.. Children of mothers given pethidine in labour were not at increased risk of cancer (odds ratio 1.05, 95% confidence interval 0.7 to 1.5) after allowing for year and hospital of delivery, but there was a significant association (p = 0.002) with intramuscular vitamin K (odds ratio 1.97, 95% confidence interval 1.3 to 3.0) when compared with oral vitamin K or no vitamin K. There was no significantly increased risk for children who had been given oral vitamin K when compared with no vitamin K (odds ratio 1.15, 95% confidence interval 0.5 to 2.7). These results could not be accounted for by other factors associated with administration of intramuscular vitamin K, such as type of delivery or admission to a special care baby unit.. The only two studies so far to have examined the relation between childhood cancer and intramuscular vitamin K have shown similar results, and the relation is biologically plausible. The prophylactic benefits against haemorrhagic disease are unlikely to exceed the potential adverse effects from intramuscular vitamin K. Since oral vitamin K has major benefits but no obvious adverse effects this could be the prophylaxis of choice.

Topics: Administration, Oral; Analgesia, Obstetrical; Child; Child, Preschool; Confounding Factors, Epidemiologic; Female; Humans; Infant; Infant, Newborn; Injections, Intramuscular; Labor, Obstetric; Meperidine; Neoplasms; Odds Ratio; Pregnancy; Risk Factors; Vitamin K 1; Vitamin K Deficiency Bleeding

Topics: Antineoplastic Agents; Child; Dactinomycin; Folic Acid Antagonists; Humans; Hyperbaric Oxygenation; Neoplasms; Oxygen; Radiation-Sensitizing Agents; Radiotherapy Dosage; Time Factors; Vitamin K 1

Topics: Aged; Antineoplastic Agents; Chloroquine; Drug Synergism; Female; Fibroblasts; Humans; Male; Neoplasms; Prednisolone; Vitamin K 1