Association of Pharmacist-led Deprescribing Intervention with the Functional Recovery in Convalescent Setting.

So far, no studies investigated the association between pharmacist intervention and rehabilitation outcomes. The aim of study was to establish whether the pharmacist-led deprescribing intervention affects rehabilitation outcomes. This retrospective, observational, single-center, cohort study included consecutive geriatric patients (n = 448) with pharmacist-led intervention between 2017 and 2019. Participants were divided based on pharmacist-led deprescribing and non deprescribing interventions during hospitalization. Demographic data, laboratory data, the Functional Independence Measure were (FIM) analyzed between the groups. Multiple linear regression analysis was performed to analyze the relationship between pharmacist-led deprescribing and FIM total gain. The primary outcome was FIM total gain. The rate of pharmacist intervention during the study period was 92.4%. A multiple linear regression analysis of FMI-T gain, adjusting for confounding factors, revealed that the pharmacist-led deprescribing intervention was independently correlated with FMI-T gain. Particularly, the use of dyslipidemia drugs, antipsychotic drugs, hypnotics, and nonsteroidal anti-inflammatory drugs significantly decreased during hospitalization. The pharmacist-led deprescribing intervention was independently and significantly associated with FIM-T gain. The pharmacist-led deprescribing intervention improved functional recovery in a rehabilitation setting.

Obesity and survival among women with ovarian cancer: results from the Ovarian Cancer Association Consortium.

BACKGROUND: Observational studies have reported a modest association between obesity and risk of ovarian cancer; however, whether it is also associated with survival and whether this association varies for the different histologic subtypes are not clear. We undertook an international collaborative analysis to assess the association between body mass index (BMI), assessed shortly before diagnosis, progression-free survival (PFS), ovarian cancer-specific survival and overall survival (OS) among women with invasive ovarian cancer. METHODS: We used original data from 21 studies, which included 12 390 women with ovarian carcinoma. We combined study-specific adjusted hazard ratios (HRs) using random-effects models to estimate pooled HRs (pHR). We further explored associations by histologic subtype. RESULTS: Overall, 6715 (54%) deaths occurred during follow-up. A significant OS disadvantage was observed for women who were obese (BMI: 30-34.9, pHR: 1.10 (95% confidence intervals (CIs): 0.99-1.23); BMI: ⩾35, pHR: 1.12 (95% CI: 1.01-1.25)). Results were similar for PFS and ovarian cancer-specific survival. In analyses stratified by histologic subtype, associations were strongest for women with low-grade serous (pHR: 1.12 per 5 kg m(-2)) and endometrioid subtypes (pHR: 1.08 per 5 kg m(-2)), and more modest for the high-grade serous (pHR: 1.04 per 5 kg m(-2)) subtype, but only the association with high-grade serous cancers was significant. CONCLUSIONS: Higher BMI is associated with adverse survival among the majority of women with ovarian cancer.

Time to first cigarette and lung cancer risk in Japan.

BACKGROUND: Cigarette smoking is the major cause of lung cancer (LC). Although the time to first cigarette (TTFC) of the day is a distinct indicator of nicotine dependence, little information is available on its possible relation to LC. PATIENTS AND METHODS: This case-control study includes a total of 1572 incident LC cases and 1572 non-cancer controls visiting for the first time the Aichi Cancer Center Hospital between 2001 and 2005. We estimated the odds ratio (OR) and 95% confidence interval (CI) for TTFC using a logistic regression model after adjustment for several potential confounders. RESULTS: TTFC was inversely associated with the risk of LC. This association was consistent across histological subtypes of LC. For all LCs considered among ever smokers and after accurate allowance for smoking quantity and duration, besides other relevant covariates, compared with TTFC >60 min, the adjusted ORs were 1.08 (95% CI, 0.73-1.61) for TTFC of 31-60 min, 1.40 (0.98-2.01) for 6-30 min and 1.86 (1.28-2.71) for within 5 min (Ptrend, < 0.001). Statistically marginally significant heterogeneity by histological subtype was observed (Pheterogeneity, 0.002). CONCLUSIONS: Nicotine dependence, as indicated by the TTFC, is associated with increased risk of LC and is therefore an independent marker of exposure to tobacco smoking.

Reproductive and hormonal risk factors for luminal, HER2-overexpressing, and triple-negative breast cancer in Japanese women.

BACKGROUND: Although the clinical relevance of the molecular subtypes of breast cancer is evident, etiological differences among subtypes have not been well established, especially among Asian. Here, we evaluated the hypothesis that the etiologic impact of reproductive and hormonal features differs among molecular subtypes. MATERIALS AND METHODS: We conducted a case-control study in pre- and postmenopausal Japanese. We examined 706 breast cancer patients and 1412 age- and menopausal status-matched noncancer controls. Immunohistochemical stains for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) were used to classify the cases into 554 luminal (hormone receptor positive), 84 HER2-overexpressing (hormone receptor negative, HER2 positive), and 68 triple-negative cases (hormone receptor negative, HER2 negative). Associations were evaluated using multivariate polytomous logistic regression models. RESULTS: A significant association was observed between early age at menarche and risk of luminal disease (odds ratios = 1.67, 95% confidence interval: 1.22-2.29; P trend = 0.001). No significant differences in association with parity, age at first live birth, breastfeeding history, age at menopause, or synthetic hormonal use were seen across molecular subtypes of breast cancer. CONCLUSIONS: These findings indicate that reproductive events in adolescence have differential impact on the risk of breast cancer molecular subtypes in Japanese.

Genetic polymorphism of IGF-I predicts recurrence in patients with gastric cancer who have undergone curative gastrectomy.

BACKGROUND: To our knowledge, no reports have evaluated the effects of genetic polymorphisms of insulin-like growth factor-I (IGF-I) on clinical outcomes of gastric cancer patients. METHODS: We retrospectively analyzed the impact of IGF-I polymorphisms on recurrence-free survival (RFS) in 430 patients with gastric cancer who underwent curative gastrectomy between 2001 and 2005 in our institution. RESULTS: Among the 430 gastric cancer patients, 345 were pathological stage I or II, while 85 were stage III or IV. The median 5-year RFS rate was 85.3% (95% confidence interval [CI] 81.4-88.5). In a multivariate Cox model (adjusted for age, gender, histology, pathological stage, adjuvant chemotherapy, and history of diabetes), two IGF-I polymorphisms, rs1520220 and rs2195239, were significantly associated with RFS (hazard ratio [HR] 0.60, 95% CI 0.40-0.91; and HR 0.60, 95% CI 0.41-0.89, respectively, in a per-allele model). When stratified by stage (I-II versus III-IV), rs1520220 in particular was associated with RFS in patients with stage III-IV disease, with a P-value for interaction of 0.01. CONCLUSIONS: Our findings indicate that genetic polymorphisms of IGF-I may have a substantial effect on recurrence for gastric cancer patients who have undergone curative gastrectomy. This information may help identify population subgroups that could benefit from IGF-I-targeting agents.

Inverse association between soy intake and non-Hodgkin lymphoma risk among women: a case-control study in Japan.

BACKGROUND: Non-Hodgkin lymphoma (NHL) is one of the common malignant tumors worldwide. Environmental factors, such as diet have an important association with the risk of cancer. Although soy intake has been associated with a reduced risk of several cancers, its association with NHL is not known. PATIENTS AND METHODS: We evaluated the association between soy consumption and risk of NHL by conducting a hospital-based case-control study in 302 patients with NHL and 1510 age- and sex-matched control subjects. Odds ratio (OR) and 95% confidence intervals (CIs) for groups with moderate (27-51 g/day) to high (>51 g/day) relative to low (<27 g/day) intake were calculated using multivariate conditional logistic regression model. RESULTS: Soy intake was significantly associated with a reduced risk of NHL in women but not in men (OR [95% CI] for moderate and high intake: women, 0.64 [0.42-1.00] and 0.66 [0.42-1.02], respectively; men, 1.40 [0.87-2.24] and 1.33 [0.82-2.15], respectively; P-interaction = 0.02). This finding appeared consistent across NHL subtypes. CONCLUSION: These results indicate the potential importance of certain ingredients in soy for lymphomagenesis. Further studies to evaluate the mechanism behind the association between soy intake and lymphomagenesis are warranted.

Association between dietary folate intake and clinical outcome in head and neck squamous cell carcinoma.

BACKGROUND: The association between dietary folate intake, two polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TYMS), and survival in head and neck squamous cell carcinoma (HNSCC) patients is not clarified. PATIENTS AND METHODS: We conducted a retrospective cohort study of 437 HNSCC patients treated at Aichi Cancer Center. We evaluated the survival impact of pretreatment dietary folate intake, which was estimated using a food-frequency questionnaire, and two polymorphisms, MTHFR C677T and a 6-bp insertion/deletion in the 3'-untranslated region of TYMS, using multivariate proportional hazard models. RESULTS: Patients with high folate intake (≥320 µg/day; n=144) had significantly higher survival than patients with low or medium folate intake (<320 µg/day; n=278; 79.1% versus 68.2%, respectively, P=0.020). This association was consistent with multivariate analyses adjusted for established prognostic factors (hazard ratio 0.56; 95% confidence interval 0.37-0.84). MTHFR and TYMS polymorphisms did not show significant association with survival, although the TYMS 6-bp insertion allele showed potential association with a reduced risk of death. Notably, no significant interaction was observed between folate intake and the two examined polymorphisms. CONCLUSIONS: High pretreatment dietary folate intake was identified as an independent prognostic factor associated with improved clinical outcomes in HNSCC patients. Further study is warranted.

Maintaining normal temperature immediately after birth in late preterm and term infants: A systematic review and meta-analysis.

AIM: Prevention of hypothermia after birth is a global problem in late preterm and term neonates. The aim of this systematic review and meta-analysis was to evaluate delivery room strategies to maintain normothermia and improve survival in late preterm and term neonates (≥34 weeks' gestation). METHODS: Medline, Embase, CINAHL, CENTRAL and international clinical trial registries were searched. Randomized controlled trials (RCTs), quasi-RCTs and observational studies were eligible for inclusion. Risk of bias for each study and GRADE certainty of evidence for each outcome were assessed. RESULTS: 25 RCTs and 10 non-RCTs were included. Room temperature of 23 °C compared to 20 °C improved normothermia [Risk Ratio (RR), 95% Confidence Interval (CI): 1.26, 1.11-1.42)] and body temperature [Mean Difference (MD), 95% CI: 0.30 °C, 0.23-0.37 °C), and decreased moderate hypothermia (RR, 95% CI: 0.26, 0.16-0.42). Skin to skin care (SSC) compared to no SSC increased body temperature (MD, 95% CI: 0.32, 0.10-0.52), reduced hypoglycemia (RR, 95% CI: 0.16, 0.05-0.53) and hospital admission (RR, 95% CI: 0.34, 0.14-0.83). Though plastic bag or wrap (PBW) alone or when combined with SSC compared to SSC alone improved temperatures, the risk-benefit balance is uncertain. Clinical benefit or harm could not be excluded for the primary outcome of survival for any of the interventions. Certainty of evidence was low to very low for all outcomes. CONCLUSIONS: Room temperature of 23 °C and SSC soon after birth may prevent hypothermia in late preterm and term neonates. Though PBW may be an effective adjunct intervention, the risk-benefit balance needs further investigation.

Low-density lipoprotein profile changes during the neonatal period.

OBJECTIVE: To investigate natural change of low-density lipoprotein (LDL) profile during the neonatal period and the impact of gestational age and birth weight on those changes. STUDY DESIGN: We measured lipid composition in LDL fraction, LDL particle size and apolipoprotein B (apoB) concentration at birth, 5 days of age and 1 month of age in 63 healthy neonates that had 37 to 41-week gestational age. RESULT: Low-density lipoprotein cholesterol and apoB concentrations increased from birth to 5 days of age, and the concentration persisted at 1 month in breast-fed and mixed-fed infants. However, in formula-fed infants, the concentration decreased at 1 month. At 5 days of age, neonates had larger and more triglyceride (TG)-rich LDL particles than at birth. At 1 month of age, LDL particles were smaller and more cholesterol rich than at 5 days of age. Single regression analyses showed that gestational age had influenced the LDL profile at birth and 5 days of age, while at 1 month milk determined the profile. CONCLUSION: The number of LDL particles increased rapidly during the first 5 days of life, and the composition of LDL particles is modulated by TG content throughout the neonatal period. Gestational age and milk, rather than birth weight, determine postnatal changes in LDL profile.

Infrequent mutation of p53 gene in hepatitis B virus positive primary hepatocellular carcinomas.

Somatic mutation of the p53 oncogene/anti-oncogene allele has been shown to be involved in many different human solid tumors. Recently, there have been reports that p53 mutations are found to occur at high frequency (50%) in aflatoxin-related human primary hepatocellular carcinomas (HCC) (Hsu et al., 1991 Nature, vol 350, p. 427; Bressac et al., 1991 Nature, vol 350, p. 429). Most strikingly, a hotspot G to T mutation at amino acid position 249 was identified. These reports appear to contradict our earlier publications that although p53 mutation is found frequently in human HCC cell lines, it is rarely found in primary tumors. In this paper, we have further examined 20 different primary HCC samples (17 were hepatitis B surface antigen positive) and their adjacent nontumourous tissues, using restriction fragment length polymorphism (RFLP) analyses. Clear loss of heterozygosity (LOH) was found in only 3 out of 20 samples. All three samples were also found to carry a point mutation within the remaining p53 allele. None of these mutations was found to be at the proposed aflatoxin hotspot of amino acid 249. All three point mutations are of somatic origin. Ten samples, randomly chosen from the remaining 17 LOH negative HCC tumors, were analyzed further by DNA sequencing and Western blot analyses. No point mutations of p53 were found. Taken together with our previous report (Hosono et al., 1991, Oncogene vol 6, p. 237-243), we conclude that p53 mutation occurs infrequently, only approximately 18%, in HBV-positive primary hepatomas from Taiwan. Furthermore, p53 mutation appears to be acquired later in tumor development at least in some HCC samples.

Molecular analysis of the p53 alleles in primary hepatocellular carcinomas and cell lines.

We have examined p53 oncogene/anti-oncogene alleles in 10 different human hepatoma cell lines and 18 primary hepatocellular carcinomas. The p53 allele in these hepatoma cell lines appears to be a frequent target of mutation as demonstrated by Southern and Northern blotting, immunoprecipitation and Western blot analysis. In general, the steady state level of p53 specific RNA or protein in these hepatoma cell lines is higher than in normal liver. However, in three out of ten cell lines, normal-sized p53 mRNA cannot be detected. In contrast, the involvement of the p53 allele in primary hepatocellular carcinoma appears to be an exceedingly rare event. Steady state levels of p53 specific RNA in primary hepatomas are practically indistinguishable from those in normal adult liver. Using the polymerase chain reaction technique, we have amplified and subcloned exons 5, 6, 7 and 8 of p53 from 10 different hepatoma samples. DNA sequence analysis of these exon subclones reveals no apparent structural alterations. Finally, synthesis of p53 specific mRNA or protein in a HepG2 human hepatoblastoma cell line does not appear to be affected by gene expression and replication of human hepatitus B virus. Surprisingly, unlike many other kinds of human solid tumors, point mutations in p53 do not appear to be important in primary tumors of hepatocellular carcinomas.

The tumor suppressor gene WT1 inhibits ras-mediated transformation.

Wilms' tumor belongs to a small group of pediatric neoplasms that have served as paradigms of human cancers in which recessive mutations play a primary role in tumorigenesis. WT1 is a candidate tumor suppressor gene that is mutationally inactivated in a proportion of both familial and sporadic Wilms' tumors. Recent studies demonstrated that WT1 can partially suppress growth of a Wilms' tumor cell line in vitro and in vivo. We investigated the ability of WT1 to inhibit the expression of the transformed phenotype in non-Wilms' tumor cells. The expression of WT1 cDNA in ras-transformed NIH3T3 cells yielded large, flat cells that exhibited complete contact-inhibition. These morphologic changes were associated with decreased proliferation, suppression of clonogenicity in soft agar and inhibition of tumor growth in nude mice. Moreover, expression of WT1 in non-transformed NIH3T3 cells resulted in similar morphologic changes and profound resistance to transformation by an activated ras oncogene. These studies suggest that tumor inhibition by WT1 in these cells may be achieved by interference with the ras-mediated signalling pathway.

WT1 expression induces features of renal epithelial differentiation in mesenchymal fibroblasts.

The WT1 tumor suppressor gene, implicated in hereditofamilial and sporadic Wilms' tumor, is required for normal renal development and is up-regulated during the mesenchymal-epithelial transition. NIH3T3 fibroblasts overexpressing WT1 were less proliferative, larger in size and more firmly attached to tissue culture plastic, suggesting an alteration of their state of differentiation. These cells were studied in vivo by subcutaneous injection into nude mice. The resulting tumors exhibited epithelioid histopathology and formed desmosome-like structures. Molecular analyses of these WT1 expressing fibroblasts grown in culture and in nude mice revealed significant alterations in the expression of many kidney epithelial markers. These studies indicate that WT1 expression can initiate features of a program of epithelial differentiation consistent with a prominent role for WT1 in the mesenchymal epithelial transition that occurs during renal development. Through this work we identified a number of novel target genes for the WT1 transcription factor, including uvomorulin, integrin alpha8 and perlecan, and suggest that WTI may activate the IGF-II gene, also implicated in the development of Wilms' tumor.

One-time umbilical cord milking after cord cutting has same effectiveness as multiple-time umbilical cord milking in infants born at <29 weeks of gestation: a retrospective study.

OBJECTIVE: To compare two strategies to potentiate the effects of placental transfusion in infants born at <29 weeks of gestation. STUDY DESIGN: Twenty infants who received one-time umbilical cord milking after umbilical cord cutting were compared with 20 infants from a previous study group who received multiple-time umbilical cord milking. The primary outcome measurements were the probability of not needing a red blood cell (RBC) transfusion during the hospital stay and the total number of RBC transfusions within 21 days after birth. RESULT: There was no significant difference in the probability of not needing a transfusion during the hospital stay (P=0.75) and the mean number of RBC transfusions given within the first 21 days of life (1.1±1.8 for the one-time umbilical cord-milking group vs 0.7±1.2 for the multiple-time umbilical cord-milking group, P=0.48). CONCLUSION: One-time umbilical cord milking after umbilical cord cutting had similar beneficial effects to multiple-time umbilical cord milking before umbilical cord cutting in very premature infants.

High-throughput genotyping of single nucleotide polymorphisms with rolling circle amplification.

BACKGROUND: Single nucleotide polymorphisms (SNPs) are the foundation of powerful complex trait and pharmacogenomic analyses. The availability of large SNP databases, however, has emphasized a need for inexpensive SNP genotyping methods of commensurate simplicity, robustness, and scalability. We describe a solution-based, microtiter plate method for SNP genotyping of human genomic DNA. The method is based upon allele discrimination by ligation of open circle probes followed by rolling circle amplification of the signal using fluorescent primers. Only the probe with a 3' base complementary to the SNP is circularized by ligation. RESULTS: SNP scoring by ligation was optimized to a 100,000 fold discrimination against probe mismatched to the SNP. The assay was used to genotype 10 SNPs from a set of 192 genomic DNA samples in a high-throughput format. Assay directly from genomic DNA eliminates the need to preamplify the target as done for many other genotyping methods. The sensitivity of the assay was demonstrated by genotyping from 1 ng of genomic DNA. We demonstrate that the assay can detect a single molecule of the circularized probe. CONCLUSIONS: Compatibility with homogeneous formats and the ability to assay small amounts of genomic DNA meets the exacting requirements of automated, high-throughput SNP scoring.

Trace elements and mineral requirements for very low birth weight infants in rickets of prematurity.

To establish mineral and trace element requirements for very low birth it is important to prevent bone mineral disorder. Those infants fed mother's milk only are thought to be at higher risk of this disorder. Both calcium and phosphorus supplementation were thought to be needed to prevent it. Copper and zinc are important as cofactors of major enzymes involved in the synthesis of collagen. These trace elements especially zinc may not be enough for very low birth weight infants fed mother's milk. At present however the relationship between these trace elements and minerals, and bone metabolic disease in preterm infants is not completely clear.

Myeloperoxidase-specific anti-neutrophil cytoplasmic autoantibodies -- related scleroderma renal crisis treated with double-filtration plasmapheresis.

A 46-year-old female patient who was diagnosed with systemic sclerosis (SSc) developed rapidly progressive renal failure without elevation of blood pressure or plasma renin concentration. Renal biopsy revealed necrotizing crescentic glomerulonephritis (pauci-immune type) and the myeloperoxidase-specific anti-neutrophil cytoplasmic autoantibodies (MPO-ANCA) titer was found to be elevated to 669 EU/ml. Methylprednisolone (MP) pulse therapy followed by prednisolone (PSL) and mizoribine (MZR) did not suppress the progression of renal failure. Therefore, we started double-filtration plasmapheresis (DFPP) which effectively removed MPO-ANCA and prevented renal failure despite the relatively low dose of immunosuppressive agents.

Insulin-like growth factor-1 and lipoprotein profile in cord blood of preterm small for gestational age infants.

Low birth weight was associated with cardiometabolic diseases in adult age. Insulin-like growth factor-1 (IGF-1) has a crucial role in fetal growth and also associates with cardiometabolic risks in adults. Therefore, we elucidated the association between IGF-1 level and serum lipids in cord blood of preterm infants. The subjects were 41 consecutive, healthy preterm neonates (27 male, 14 female) born at <37-week gestational age, including 10 small for gestational age (SGA) infants (<10th percentile). IGF-1 levels and serum lipids were measured in cord blood, and high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC) and very low-density lipoprotein triglyceride (VLDLTG) levels were determined by HPLC method. SGA infants had lower IGF-1 (13.1 ± 5.3 ng/ml), total cholesterol (TC) (55.0 ± 14.8), LDLC (21.6 ± 8.3) and HDLC (26.3 ± 11.3) levels, and higher VLDLTG levels (19.0 ± 12.7 mg/dl) than in appropriate for gestational age (AGA) infants (53.6 ± 25.6, 83.4 ± 18.9, 36.6 ± 11.1, 38.5 ± 11.6, 8.1 ± 7.0, respectively). In simple regression analyses, log IGF-1 correlated positively with birth weight (r = 0.721, P < 0.001), TC (r = 0.636, P < 0.001), LDLC (r = 0.453, P = 0.006), and HDLC levels (r = 0.648, P < 0.001), and negatively with log TG (r = -0.484, P = 0.002) and log VLDL-TG (r = -0.393, P = 0.018). Multiple regression analyses demonstrated that IGF-1 was an independent predictor of TC, HDLC and TG levels after the gestational age and birth weight were taken into account. In preterm SGA infants, cord blood lipids profile altered with the concomitant decrease in IGF-1 level.

Association between serum lipoprotein lipase mass concentration and subcutaneous fat accumulation during neonatal period.

BACKGROUND/OBJECTIVES: Subcutaneous adipose tissue grows rapidly during the first months of life. Lipoprotein lipase (LPL) has a quantitatively important function in adipose tissue fat accumulation and insulin-like growth factor-I (IGF-I) is a determinant of neonatal growth. Recent studies showed that LPL mass in non-heparinized serum (LPLm) was an index of LPL-mediated lipolysis of plasma triacylglycerol (TG). The objective was to know the influence of serum LPL and IGF-I on neonatal subcutaneous fat growth, especially on catch-up growth in low birth weight infants. SUBJECTS/METHODS: We included 47 healthy neonates (30 males, 17 females), including 7 small for gestational age. We measured serum LPLm and IGF-I concentrations at birth and 1 month, and analyzed those associations with subcutaneous fat accumulation. RESULTS: Serum LPLm and IGF-I concentrations increased markedly during the first month, and positively correlated with the sum of skinfold thicknesses both at birth (r=0.573, P=0.0001; r=0.457, P=0.0035) and at 1 month (r=0.614, P<0.0001; r=0.787, P<0.0001, respectively). In addition, serum LPLm concentrations correlated inversely to very low-density lipoprotein (VLDL)-TG levels (r=-0.692, P<0.0001 at birth; r=-0.429, P=0.0052 at 1 month). Moreover, the birth weight Z-score had an inverse association with the postnatal changes in individual serum LPLm concentrations (r=-0.639, P<0.0001). CONCLUSIONS: Both serum LPLm and IGF-I concentrations were the determinants of subcutaneous fat accumulation during the fetal and neonatal periods. During this time, LPL-mediated lipolysis of VLDL-TG may be one of the major mechanisms of rapid growth in subcutaneous fat tissue. Moreover, LPL, as well as IGF-I, may contribute to catch-up growth in smaller neonates.

Association between dietary calcium and vitamin D intake and cervical carcinogenesis among Japanese women.

BACKGROUND/OBJECTIVES: To examine the association between dietary calcium and vitamin D intake and cervical neoplasia risk, we conducted a case-control study. SUBJECTS/METHODS: We selected 405 incident cervical neoplasias (333 invasive carcinomas and 72 cervical intraepithelial neoplasias grade III (CIN3)) and 2025 age-matched non-cancer controls. Dietary information was collected using a semiquantitative food-frequency questionnaire (FFQ). The effect on cervical neoplasia risk was evaluated using conditional logistic regression models. RESULTS: The inverse association between invasive carcinoma and milk, yogurt and fish was observed. On the other hand, the marginally significant inverse association between CIN3 and tofu and green leafy vegetables was observed. Compared with the lowest quartile (Q1) of calcium intake, adjusted odds ratios (ORs) for each of the three upper quartiles (Q2, Q3 and Q4) on invasive carcinoma risk were 0.86 (95% confidence interval (CI) 0.63-1.17), 0.50 (95% CI 0.34-0.73) and 0.68 (95% CI 0.48-0.97), respectively (P for trend=0.004). However, no association between calcium and cancer risk was evident among CIN3 cases (P for trend=0.528). Vitamin D intake showed a similar inverse association (Q2: OR 1.03, 95% CI 0.74-1.44; Q3: OR 0.80, 95% CI 0.56-1.15; and Q4: OR 0.64, 95% CI 0.43-0.94; P for trend=0.013). Similar to calcium, no association between vitamin D intake among CIN3 was evident (P for trend=0.109). An inverse association with calcium was evident in women whose vitamin D intake was low. However, this combined effect was not significant (invasive carcinoma: interaction P=0.819; and CIN3: interaction P=0.101). CONCLUSION: We found an inverse association between dietary calcium and vitamin D intake and cervical neoplasia risk among a group of Japanese women.