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J D Potter

Publications and source records attributed to J D Potter.

At least 199 records · Page 11Linked to original sources
PubMed1993

Familial clustering of colon, breast, uterine, and ovarian cancers as assessed by family history.

The aggregation of colon, endometrial, ovarian, and possibly breast cancers in families has been described as a "cancer family syndrome" (now called Lynch syndrome II). To determine if the familial clustering of these malignancies was more common in women with cancer than without, we analyzed data from the Iowa Women's Health Study (IWHS), a population-based sample of 41,837 women aged 55-69 years. Self-reported information was collected on history of colon, uterine, ovarian, and breast cancers in female first-degree relatives. A family history of cancer of the breast (odds ratio [OR] = 1.4), colon (OR = 1.3), and uterus (OR = 1.3), but not ovary (OR = 1.2), was significantly more common among women with a personal history of any of these four cancers (all P < 0.05); the pattern of the ORs suggested strongly that the clustering tended to be site-specific. Age-adjusted relative risks (RR) of incident colon cancer over 5 years of follow-up (N = 237) were calculated with regard to family history. Colon cancer incidence was increased among women with a family history of breast (RR = 1.3), uterine (RR = 1.4), colon (RR = 1.5), and ovarian (RR = 1.3) cancers, although none of the risk estimates achieved statistical significance. RR was, however, significantly related to the number of different cancer sites reported among family members (Ptrend = 0.008). These data on a representative sample of postmenopausal women suggest that family histories of colon, breast, uterine, and ovarian cancers are associated with an increased risk of cancer at the same site, but provide little support for the hypothesis that Lynch syndrome II is a non-random occurrence.

Aged↗
PubMed1993

Knowledge, attitudes, and personal practices regarding prevention and early detection of cancer.

METHODS: To determine population knowledge, attitudes, and personal practices regarding prevention and early detection of cancer, random population samples of 25- to 74-year-old men and women in six various-sized communities in three upper-midwestern states (N = 4,915) were administered surveys and interviews during 1987-1989. RESULTS: Four-fifths of respondents believed cancer to be preventable. Knowledge of warning signs/symptoms of cancer and of leading causes of cancer, however, was low. Over 95% of women had had a Papanicolaou smear and a clinical breast exam or had performed a breast self-exam; 65.7% of those ages 50-65 years had had a mammogram. Among men and women ages 50-65 years, 77% had had a digital rectal exam; 52.5%, a fecal occult blood test; and 48.3%, a sigmoidoscopy. CONCLUSIONS: Conditions are favorable for an increase in mammography, including favorable attitudes toward cancer prevention, strong consensus among policy-making organizations regarding guidelines for obtaining mammograms, and high levels of adherence to these recommendations by women who have had at least their first mammogram. Challenges now include acceptance of these guidelines by physicians, mammogram affordability/availability, and demonstration of efficacious, cost-effective, and reliable colorectal/prostate cancer screening tests.

Adult↗
PubMed1993

Alcohol consumption and postmenopausal endometrial cancer: results from the Iowa Women's Health Study.

At least three case-control studies have examined the association between alcohol consumption and endometrial cancer; two studies showed inverse associations, and a third a positive association. To our knowledge, no prospective studies of this association have been reported. The association between alcohol and endometrial cancer was examined in the Iowa Women's Health Study (United States), a prospective study of postmenopausal women. Information on alcohol consumption and other variables was obtained through a mailed questionnaire in January 1986. Through December 1990, 167 incident endometrial cancer cases occurred in the at-risk cohort of 25,170 women. Multivariate-adjusted relative risks (RR) and 95 percent confidence intervals (CI) were computed using Cox proportional hazards regression controlling for age, body mass index (BMI), parity, age at menopause, and noncontraceptive estrogen use, and to determine multiplicative interactions. The RRs of endometrial cancer associated with < 4.0 and > or = 4.0 g of alcohol per day compared with abstainers were 0.7 (CI = 0.5-1.1) and 1.0 (CI = 0.7-1.6), respectively. No statistically significant association between endometrial cancer and consumption of either beer, wine, or liquor was observed. There was no interaction between alcohol and any other endometrial cancer risk factors, including BMI or noncontraceptive estrogen use. These data do not support an association between alcohol and endometrial cancer among postmenopausal women.

Age Factors↗
PubMed1993

Difficulty becoming pregnant and family history as interactive risk factors for postmenopausal breast cancer: the Iowa Women's Health Study.

We recently provided data from a prospective cohort study of postmenopausal women which suggested that a first livebirth at age 30 or older (cf before age 20) was associated with a twofold increased risk of breast cancer in women without a family history, but a 5.8-fold higher risk in women with a positive family history. To address the question of whether these observations reflect difficulty becoming pregnant or maintaining a pregnancy, we performed additional analyses in which the outcome of each pregnancy was considered. During five years of follow-up, 620 incident cases of breast cancer were identified in the 37,105 women at risk. There was little evidence for an increased risk associated with a history of spontaneous abortion (relative risk [RR] = 1.1; 95 percent confidence interval [CI] = 0.9-1.4), nor was the risk higher among women who reported two or more spontaneous abortions in consecutive pregnancies (RR = 1.0, CI = 0.7-1.4). Although women who reported that they had tried unsuccessfully to become pregnant had only slightly and nonsignificantly elevated risks of breast cancer (RR = 1.1, CI = 0.9-1.3), a more pronounced and statistically significant association was noted in women with a positive family history (RR = 2.1, CI = 1.4-3.2). There was a strong inverse association between failure to become pregnant and parity (P < 0.0001); nearly 50 percent of the nulliparous married women reported having tried and failed to become pregnant, whereas the frequency was only 6.8 percent among married women with five or more livebirths.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Spontaneous↗
PubMed1993

Determination of the Ca2+ and Mg2+ affinity constants of troponin C from eel skeletal muscle and positioning of the single tryptophan in the primary structure.

The complete amino acid sequence of troponin C (ETnC) from the white muscle of the European eel has been determined by Edman degradation procedures. Its single tryptophan residue is situated in helix H at amino acid position 152 of the aligned sequence; the tryptophan is the first residue on the C-terminal side of Ca2+ binding loop IV. The increase of tryptophan fluorescence emission intensity occurring upon titration of ETnC with Ca2+ has been used to determine the affinity constants of ETnC for Ca2+. The calculated affinity of ETnC for Ca2+ results in a K(Ca) of 1.3 10(7) M-1, typical of the Ca(2+)-Mg2+ sites of the second domain of fast skeletal muscle TnCs. Moreover, a direct competition between Ca2+ and Mg2+ was also observed. The calculated affinity of ETnC for Mg2+ is K(Mg) = 1.2 10(3) M-1. In order to probe the affinity constants of the Ca2+ binding sites of the regulatory domain, ETnC was labelled with dansylaziridine (Danz). The Danz fluorescent signal was used to estimate the affinity constants of ETnC-Danz for Ca2+ and also for Mg2+ (assuming a competitive behaviour between these two metal ions). The calculated affinity constants are K(Ca) = 9.4 10(5) M-1 and K(Mg) = 2.0 10(2) M-1, respectively. These values are typical of the Ca(2+)-specific sites of the regulatory domain of fast skeletal muscle TnCs.

Amino Acid Sequence↗
PubMed1993

Colon cancer--do the nutritional epidemiology, the gut physiology and the molecular biology tell the same story?

Colon carcinogenesis models exist at epidemiologic, physiologic and molecular biologic levels. Thinking about the coherence of such models is useful both to inform colon cancer research and because the reasoning process may be generalizable. The consistent epidemiologic risk factors are low vegetable/fiber and high fat/meat/protein intakes. Others include physical activity, alcohol and reproduction. These epidemiologic risk factors appear to map to physiologic variables that provide mechanistic explanations for the associations: higher bile acids, fiber fermentation and effects of specific anticarcinogens found in vegetables. The possibility that the meat/fat association is due to carcinogens or promoters produced in cooked foods adds complexity to the physiologic model. As a link across genetics, physiology and epidemiology, the role of acetylator status is considered. Finally, whether relationships might exist between the epidemiologic/physiologic risk factors and the recently described molecular genetic changes and other colon cancer molecular mechanisms is considered.

Colonic Neoplasms↗
PubMed1993

Platelet-derived growth factor and risk factors for colorectal cancer.

Platelet-derived growth factor (PDGF) is a potent mitogen for a variety of cells. Abnormal PDGF activity has been reported in many chronic diseases including cancer. Existing data suggest that fluctuations or reset homeostasis in normal growth factor production due to specific agents or changes in cellular environment are potential mechanisms of colonic carcinogenesis. Currently identified risk factors for colorectal cancer include diet, non-steroidal anti-inflammatory drug use, alcohol consumption and physical activity. Certain constituents of diet, including retinoids, fish oils and soybeans, inhibit the activity of PDGF and could reduce paracrine stimulation of the colonic epithelium. Aspirin and physical activity, through reduction in platelet aggregation, may inhibit platelet release of PDGF and lead to reset homeostasis. Alcohol affects platelet aggregation and, depending on consumption patterns, could alter platelet release of PDGF. It is important to determine which of these environmental factors may result in transient effects on growth factor activity and which result in long-term adaptive responses. Further studies could examine the impact of these risk factors on (1) growth factor communication between colonic epithelial cells and fibroblasts in vitro and (2) PDGF concentrations and mitogenic activity in blood and tissue obtained in population-based studies of colorectal cancer.

Alcohol Drinking↗
PubMed1993

Sex differences in colonic function: a randomised trial.

There are sex differences in large bowel cancer rates and a variety of other gastrointestinal disorders possibly because of differences in gut biology. To determine whether men and women have different gastrointestinal responses when consuming identical intakes of dietary fibre, 16 women and 18 men consumed liquid formula diets and 'quick breads' with 0 g, and 10 g, and 30 g of fibre as wheat bran and vegetable fibre. The five test diets were consumed in random order, each treatment lasting 23 days. Mean transit time was faster (p = 0.02), and stool weights (g/day) were greater (p = 0.0005) for men than women. Neutral detergent fibre (NDF) excretion was greater in men (p = 0.01), and women tended to digest more NDF (p = 0.06). Men and women seemed to respond differently to wheat bran and vegetable fibre with regard to NDF excretion and digestibility. There were no gender differences in the faecal pH or moisture content. Concentrations and daily excretion of the secondary bile acids, lithocholic and deoxycholic acid, were greater for men than women (p < 0.05). Gender differences in bowel function and bile acid excretion, observed when men and women consumed the same amounts of dietary fibre, may be relevant for understanding colonic disease aetiology and for undertaking future dietary intervention trials.

Adolescent↗
PubMed1992

Isolation, expression, and mutation of a rabbit skeletal muscle cDNA clone for troponin I. The role of the NH2 terminus of fast skeletal muscle troponin I in its biological activity.

A cDNA for rabbit fast skeletal muscle troponin I (TnI) was isolated and sequenced. The clone contains a coding sequence predicting a 182-amino-acid protein with a molecular mass of 21,162 daltons. The translated sequence is different from that reported by Wilkinson and Grand (Wilkinson, J. M., and Grand, R. J. A. (1978) Nature 271, 31-35) in that Arg-153, Asp-154, and Leu-155 must be inserted into their original sequence. Amino acid sequencing of adult rabbit TnI confirmed this result. In order to investigate the role of the NH2 terminus of TnI in its biological activity, we have expressed a recombinant deletion mutant (TnId57), which lacks residues 1-57, in a bacterial expression system. Both wild type TnI (WTnI) and TnId57 inhibited acto-S1-ATPase activity and this inhibition could be fully reversed by troponin C (TnC) in the presence of Ca2+. Additionally both WTnI and TnId57 bound to an actin affinity column. Thus, both inhibitory actin binding and Ca(2+)-dependent neutralization by TnC were retained in TnId57. TnC affinity chromatography was used to compare the binding of TnI and TnId57 to TnC. Using this method, two types of interaction between TnC and TnI were observed: 1) one which is metal independent (or structural) and 2) one dependent on Ca2+ or Mg2+ binding to the Ca(2+)-Mg2+ sites of TnC. The same experiments with TnId57 demonstrated that the type 1 interaction was weakened, and type 2 binding was lost. This method also revealed an interaction between TnC and TnI which is dependent upon Ca2+ binding to the Ca(2+)-specific sites of TnC and which is retained in TnId57. Taken together, these results suggest that the NH2 terminus of TnI may constitute a Ca(2+)-Mg(2+)-dependent interaction site between TnC and TnI and play, in part, a structural role in maintaining the stability of the troponin complex while the COOH terminus of TnI contains a Ca(2+)-specific site-dependent interaction site for TnC as well as the previously demonstrated Ca(2+)-sensitive inhibitory and actin binding activities.

Actins↗
PubMed1992

Increased risk of breast cancer with alcohol consumption in postmenopausal women.

The association between breast cancer incidence and alcohol consumption among postmenopausal women was examined in the Iowa Women's Health Study. In January 1986, a cohort of 41,837 postmenopausal women, aged 55-69 years, completed a questionnaire that included alcohol intake and other information. Through December 1989, 493 incident breast cancer cases were identified. Age-adjusted relative risks of consumption of less than 1.5, 1.5-4.9, 5.0-14.9, and 15.0 g or more of alcohol per day compared with abstention were 1.08, 1.10, 1.08, and 1.28, respectively (p for trend = 0.11). After controlling for age, body mass index, age at first livebirth, age at menarche, and family history of breast cancer, the relative risks were 1.18, 1.20, 1.25, and 1.46 (p for trend = 0.04). Multivariate modeling, using Cox proportional hazards regression, revealed a significant multiplicative interaction between alcohol intake and noncontraceptive estrogen use. The relative risks of breast cancer associated with average daily alcohol consumption of 5.0-14.9 and 15.0 g or more were 1.88 (95% confidence interval 1.30-2.72) and 1.83 (95% confidence interval 1.18-2.85), respectively, among ever-users of estrogen; no association between alcohol and breast cancer was observed among never-users of estrogen.

Aged↗
PubMed1992

Two genetically expressed troponin T fragments representing alpha and beta isoforms exhibit functional differences.

The carboxyl-terminal isoforms of troponin T (TnT), alpha and beta, differing in the sequence of a region near the COOH terminus, arise from alternative splicing of a primary transcript of the TnT gene and are expressed in a tissue-specific and developmentally regulated manner (Medford, R. M., Nguyen, H. T., Destree, A. T., Summers, E., and Nadal-Ginard, B. (1984) Cell 38, 409-421). To date, the beta isoform has not been studied directly at the protein level. To explore the potential functional differences between the alpha and beta sequences, we isolated two rabbit skeletal TnT cDNA clones: a full-length cDNA for a beta isoform and a partial-length cDNA for an alpha isoform. Two restriction fragments derived from the cDNA clones were used to direct overexpression, in Escherichia coli, of two TnT fragments, T2p-alpha and T2p-beta, each containing the last 108 amino acid residues of the alpha or beta isoform of TnT. Using purified T2p-alpha and T2p-beta along with fluorescent derivatives of troponin C (TnC) and alpha alpha-tropomyosin (Tm), we showed that T2p-alpha bound more strongly to TnC than did T2p-beta both in the presence and absence of Ca2+, and exhibited a higher affinity for Tm than did T2p-beta. More interestingly, the Ca2+ affinities of the Ca(2+)-specific regulatory sites of TnC in the T2p-alpha. TnC complex were found to be 3-fold higher than in T2p-beta.TnC complex. These results support the hypothesis that the sequence divergence between the alpha and beta isoforms of TnT may have functional significance in possibly contributing to the determination of the Ca2+ sensitivity of muscle fibers.

Amino Acid Sequence↗
PubMed1992

Dietary fat and postmenopausal breast cancer.

BACKGROUND: Although the results of animal studies and cross-cultural comparisons generally support a role for dietary fat in the etiology of breast cancer, results of analytic epidemiology studies are equivocal. PURPOSE: The association between dietary fat and subsequent breast cancer was examined in a cohort of 34,388 postmenopausal women from Iowa. METHODS: Dietary habits were assessed by a food-frequency questionnaire mailed in January 1986. Through December 31, 1989, 459 incident cases of breast cancer occurred in this cohort. Proportional hazards regression was used to examine the dietary fat-breast cancer association while adjusting for potential confounders. The effects on this association of four analytic approaches to adjustment for energy intake were also considered. RESULTS: After adjustment for known determinants of breast cancer, a modest positive association of total fat intake with risk of breast cancer was seen. Polyunsaturated fat intake was also positively associated with breast cancer (relative risk from lowest to highest intake, 1.0, 1.25, 1.31, and 1.49; P for trend = .052). Different approaches to adjustment for energy intake, however, provided different impressions of the dietary fat-breast cancer association. One method, involving categorization of crude fat intake and inclusion of total energy intake in regression analysis, gave relative risk estimates from low to high fat intake of 1.0, 1.17, 1.25, and 1.38 (P for trend = .18). Another method, based on categorization of fat intake residuals in which the variation in fat due to total energy intake was removed, gave corresponding estimates of 1.0, 1.24, 1.30, and 1.16 (P for trend = .29). The former suggests increasing breast cancer risk with increasing fat intake; the latter suggests no association. CONCLUSIONS: These results are consistent with other cohort studies that have shown a weak association or no association between dietary fat and breast cancer. They are also consistent with studies suggesting that fat intake is a determinant of breast cancer, particularly after accounting for inaccuracies in dietary assessment. The effects of different energy-adjustment methods may account in part for the varying interpretations of four previous cohort studies of dietary fat and breast cancer. IMPLICATIONS: Further work is needed to clarify not only the nature of the dietary fat-breast cancer association, but also the impact of different analytic methods used in the investigation of diet-disease associations.

Aged↗
PubMed1992

Effect of family history, body-fat distribution, and reproductive factors on the risk of postmenopausal breast cancer.

BACKGROUND: A family history of breast cancer reflects shared cultural factors, genetic predisposition, or both. There is evidence that the estimated risk associated with a family history of breast cancer increases multiplicatively in combination with other risk factors. We examined the combined effect of family history and anthropometric and reproductive factors on the risk of breast cancer in postmenopausal women. METHODS: Using data from a prospective cohort study, we studied 37,105 women 55 to 69 years of age to determine whether known risk factors for breast cancer are modified by a reported family history at the time of entry into the study. RESULTS: During the first 4 years of follow-up, 493 new breast cancers were diagnosed. The association of the waist-to-hip ratio (the circumference of the waist divided by that of the hips) with the risk of breast cancer was limited predominantly to women with a family history of breast cancer; the age-adjusted relative risk of breast cancer for the women above the fourth quintile for waist-to-hip ratio as compared with those below the first quintile was 3.2 in women with a family history of breast cancer and 1.2 for women without such a family history. An interaction was observed between a family history of breast cancer and the number of live-born children; the protective effect of higher parity was observed primarily among women with a family history of breast cancer. Similarly, the age-adjusted relative risk of breast cancer associated with a late age at first pregnancy (i.e., greater than or equal to 30 years) was 5.8 for women with a family history of breast cancer and 2.0 for women without such a family history. CONCLUSIONS: The increase in the risk of breast cancer associated with a high waist-to-hip ratio, low parity, or greater age at first pregnancy is more pronounced among women with a family history of breast cancer. These findings suggest etiologic differences between familial breast cancer and the sporadic form.

Adipose Tissue↗
PubMed1992

Lung cancer detection and prevention: evidence for an interaction between smoking and genetic predisposition.

The initiation and promotion of cancer is thought to result from a series of genetic mutations, some of which may be inherited. Our analysis of 337 lung cancer families suggested that, after allowing for an individual's pack-years of tobacco use, the pattern of disease was best explained by Mendelian codominant inheritance of an allele that produced earlier age of onset. Since lung cancer rarely occurs in the absence of exposure to tobacco, differences in the prevalence of smoking across generations could have a profound influence on the fit of genetic models. In the present study, families were partitioned into two groups, based on the birth cohort of the proband, i.e., born before World War I (age at death, greater than or equal to 60 years) or born after World War I (age at death, less than 60 years). This partition was chosen because the year 1915 signaled the start of the dramatic rise in tobacco use in the United States. In younger proband families, in which parents were more likely to smoke, Mendelian codominant inheritance provided the best fit to the data. In older proband families, for whom smoking among parents was less prevalent, the "no major gene" and "environmental" hypotheses were rejected; however, no Mendelian models could be distinguished. If the results on the families with the most homogeneous exposure to tobacco across generations (born after World War I) reflect the true underlying biology, then the influence of genetic factors in the pathogenesis of lung has been underestimated; the cumulative probability of lung cancer at age 80 for a noncarrier of the gene, at the average level of tobacco consumption, is close to zero, implying that virtually all lung cancer occurs among gene carriers. Identification of this putative genetic factor has profound implications for the detection and prevention of lung cancer.

Aged↗
PubMed1992

Effect of cohort differences in smoking prevalence on models of lung cancer susceptibility.

Data on 337 lung cancer families were analyzed to determine if known cohort differences in parental cigarette consumption influence parameters from a segregation analysis. Previous results suggested that, after allowing for an individual's pack-years of tobacco exposure, Mendelian codominant inheritance of an allele that produced an earlier age of onset provided a good fit to the data. In the present study, the data were split into two groups of families: probands age 60 and over (born before WWI) and probands younger than age 60. This partition of the data by age of the proband was done to separate families in which there were parents who were less likely to smoke from those with parents more likely to smoke--predicated on the known increase of smoking prevalence after World War I. For the younger proband families (those with parents more likely to smoke), only Mendelian codominant inheritance adequately fit the data. The hypotheses of no major type, environmental transmission, and Mendelian dominant or recessive inheritance were rejected. In contrast to our earlier findings, the estimate of population susceptibility increased from 28% in the total data to 60% in this subset. In the older proband families (those with parents less likely to smoke), the no major type and environmental hypotheses were rejected; further, none of the Mendelian models could be distinguished. Our results demonstrate that cohort differences, probably in exposure to tobacco, can confound parameters of a segregation analysis, and suggest that the genetic component of lung cancer may be greater than previously estimated. It further suggests that susceptibility to lung cancer occurs as a function of susceptibility to the effects of tobacco smoking.

Adult↗
PubMed1992

A monoclonal antibody that recognizes different conformational states of skeletal muscle troponin C and other calcium binding proteins.

Skeletal muscle troponin C contains four Ca(2+)-binding sites, two with a high affinity for Ca2+ that also bind Mg2+ competitively (Ca2+/Mg2+ sites) and two sites of lower affinity that are specific for Ca2+. We have characterized a monoclonal antibody (B9D9) that was produced against rabbit skeletal troponin C. The binding of this antibody to rabbit skeletal troponin C is sensitive to the binding of Ca2+. Increasing the Ca2+ concentration produces a decrease in the amount of antibody bound with a pK of approximately 6.9 which correlates with Ca2+ binding to the Ca2+/Mg2+ sites. Magnesium binding to rabbit skeletal troponin C had no effect on antibody binding. Thus the conformation of rabbit skeletal troponin C brought about by Ca2+ binding to these sites affects the antibody binding to its epitope. This epitope was unavailable for antibody binding in whole troponin. The antibody-binding site was localized in cyanogen bromide fragment CB9 of rabbit skeletal troponin C (residues 84-135). This antibody was also shown to cross-react with bovine cardiac troponin C, barnacle (Balanus nubilus) troponin C, bovine testis calmodulin and carp parvalbumin. In addition, the effect of Ca2+ on antibody binding seen with rabbit skeletal troponin C was also seen with bovine cardiac troponin C, and calmodulin. Thus these proteins appear to share a similar epitope and undergo similar structural changes. Wang and colleagues (1987) have presented evidence that rabbit skeletal troponin C at low pH has an elongated structure similar to that seen in the crystal structure and that at neutral pH its structure is more compact.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗