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ABSTRACT: Routine breast cancer follow-up aims at detecting second primary breast cancers and loco regional recurrences preclinically. We studied breast cancer follow-up practice and mode of relapse detection during the first 5 years of follow-up to determine the efficiency of the follow-up schedule. The Netherlands Cancer Registry provided data of 6,509 women, operated for invasive non-metastatic breast cancer in 2003-2004. In a random sample including 144 patients, adherence to follow-up guideline recommendations was studied. Mode of relapse detection was studied in 124 patients with a second primary breast cancer and 160 patients with a loco regional recurrence. On average 13 visits were performed during the first 5 years of the follow-up, whereas nine were recommended. With one, two and three medical disciplines involved, the number of visits was 9, 14 and 18, respectively. Seventy-five percent (93/124) of patients with a second primary breast cancer, 42 % (31/74) of patients with a loco regional recurrence after breast conserving surgery and 28 % (24/86) of patients with a loco regional recurrence after mastectomy had no symptoms at detection. To detect one loco regional recurrence or second primary breast cancer preclinically, 1,349 physical examinations versus 262 mammography and/or MRI tests were performed. Follow-up provided by only one discipline may decrease the number of unnecessary follow-up visits. Breast imaging plays a major and physical examination a minor role in the early detection of second primary breast cancers and loco regional recurrences. The yield of physical examination to detect relapses early is low and should therefore be minimised.
Breast Cancer Research and Treatment 11/2012; · 4.43 Impact Factor
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ABSTRACT: Background: Thyrotoxicosis and hypothyroidism are associated with fatigue. Here we studied euthyroid subjects to determine if there was a relationship between serum thyrotropin (TSH), free thyroxine (FT(4)) and thyroperoxidase antibodies and fatigue. Methods: A total of 5897 participants of the Nijmegen Biomedical Study received a questionnaire and serum TSH (normal range 0.4-4.0 mIU/L) and FT(4) (normal range 8-22 pmol/L) were measured. Fatigue was evaluated by the RAND-36 and the shortened fatigue questionnaire (SFQ). Results: Euthyroid subjects with a serum TSH level of 0.4-1.0 mIU/L had a lower RAND-36 vitality score (65.2 vs. 66.8; regression coefficient (RC) -1.6 [95% confidence interval (CI) -2.6 to -0.5]; p=0.005) and a higher SFQ score (11.7 vs. 11.0; RC 0.6 [CI 0.2-1.0]; p=0.004) than those with a TSH of 1.0-2.0 mIU/L. Those with a serum FT(4) of 18.5-22 pmol/L reported fatigue more often (52.5% vs. 33.3%; relative risk (RR) 1.4 [CI 1.0-1.9]; p=0.03), had a lower RAND-36 vitality score (61.7 vs. 66.6; RC-4.4 [CI -8.1 to -0.6]; p=0.02) and a higher SFQ score (13.2 vs. 11.0; RC 1.9 [CI 0.4-3.3]; p=0.01) than subjects with a FT(4) level of 11.5-15 pmol/L. In comparison to euthyroid subjects without known thyroid disease, euthyroid subjects with previously known thyroid disease reported fatigue more often (52.3% vs. 34.0%; RR 1.3 [CI 1.0-1.5]; p=0.025), had a lower RAND-36 vitality score (61.4 vs. 66.3; RC -2.9 [CI -5.3 to -0.6]; p=0.015) and a higher SFQ score (13.7 vs. 11.1; RC 1.4 [CI 0.5-2.3]; p=0.002). Conclusion: In euthyroid individuals without a history of thyroid disease, there is a modest relationship between thyroid function and fatigue with subjects having an apparently higher production of T(4) experiencing more fatigue. Subjects with a history of thyroid disease, but with normal TSH and FT(4) concentrations, experience more fatigue than the general population. The reasons for this are unclear, but subtle abnormalities in the dynamics of thyroid hormone secretion should be considered.
Thyroid: official journal of the American Thyroid Association 09/2012; · 2.60 Impact Factor
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ABSTRACT: The clinical benefit of routine follow-up in patients treated for ovarian cancer is subject to debate. In this study, the magnitude of the potential survival benefit of routine examinations was evaluated by Markov modeling.
The clinical course of ovarian cancer was simulated using a 4-state nonstationary Markov model. Risk of recurrence and mortality probabilities were derived from individual patient data and Statistics Netherlands. The life expectancy was simulated for 3 follow-up scenarios: a current, withholding (all recurrences detected symptomatically), and perfect follow-up program (all recurrences detected asymptomatically). The impact of effective recurrence treatment in the future was modeled by varying the mortality ratio between patients with asymptomatically versus symptomatically detected recurrences. The model was validated using empirical data.
The mean life expectancy of patients, aged 58 years and in complete clinical remission after primary treatment, was 10.8 years. Varying the transition probabilities with ±25% changed the life expectancy by up to 1.1 years. The modeled life expectancy for the withholding and perfect follow-up scenarios was also 10.8 years and insensitive to model assumptions. In patients with stages IIB to IV, the life expectancy was 7.0 years, irrespective of follow-up strategy. A mortality ratio of 0.8 for patients with asymptomatically versus symptomatically detected recurrences resulted in a gain in life expectancy of 5 months for withholding versus perfect follow-up.
Routine follow-up in ovarian cancer patients is not expected to improve the life expectancy. The timing of detection of recurrent ovarian cancer is immaterial until markedly improved treatment options become available.
International Journal of Gynecological Cancer 08/2012; 22(7):1150-7. · 1.65 Impact Factor
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ABSTRACT: To explore the utility of the novel iron indices hepcidin, reticulocyte hemoglobin content (Ret-Hgb), and erythrocyte (red blood cell) hemoglobin content (RBC-Hgb) for detection of iron deficiency in rheumatoid arthritis (RA) patients with anemia and active inflammation and to compare these indices with conventional parameters of iron deficiency.
Blood samples from 106 outpatients with RA were analyzed in a cross-sectional exploratory study. Forty patients were classified as having either iron deficiency anemia (IDA), anemia of chronic disease (ACD), their combination (IDA/ACD), or "other anemia" based on biochemical parameters for inflammation and iron deficiency. The ability of serum and urine hepcidin, Ret-Hgb, and RBC-Hgb measurement to discriminate among these states was evaluated.
Hepcidin content in serum from patients in the IDA group as well as that from patients in the combined IDA/ACD group differed significantly from that in serum from patients in the ACD group. This difference was also observed with hepcidin in urine, Ret-Hgb, and RBC-Hgb, although with less significance. The area under the receiver operating characteristic curve for serum hepcidin was 0.88 for the comparison of IDA/ACD patients with ACD patients and 0.92 for the comparison of the combined IDA group and IDA/ACD group to all other patients with anemia. Hepcidin at <2.4 nmoles/liter had a sensitivity of 89% and a specificity of 88% to distinguish IDA/ACD from ACD. Both Ret-Hgb and RBC-Hgb measurements also allowed differentiation between these latter groups, with a sensitivity of 67% and 89%, respectively, and a specificity of 100% and 75%, respectively.
Serum hepcidin and, to a lesser extent, urine hepcidin, Ret-Hgb, and RBC-Hgb, are potential useful indicators for detecting iron deficiency in RA patients with anemia and active inflammation.
Arthritis & Rheumatism 12/2011; 63(12):3672-80. · 7.87 Impact Factor
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Transfusion 07/2011; 51(9):1883-5. · 3.22 Impact Factor
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ABSTRACT: Patients treated for ovarian cancer with curative intent receive an intensive follow-up program in the years after treatment. However, the aimed improved survival through early detection of recurrence is subject to debate. Theoretically, the survival benefit depends on the lead time and the preclinical detection rate and on the effectiveness of recurrence treatment. This systematic review aimed at determining the effectiveness of early detection of recurrent ovarian cancer.
A systematic literature search in PubMed, EMBASE, MEDLINE, and the Cochrane Library was performed for articles published in 1985 to 2009 in English, German, or Dutch, excluding editorials, letters, and case reports.
In total, 67 articles were included. Of 4 observational studies and 1 randomized controlled trial, only 1 observational study reported a better survival for patients who attended routine follow-up compared with those who did not. The sensitivity of cancer antigen 125 for a preclinical recurrence, based on 38 articles using 35 U/mL as a cutoff level, was 65%, with a median lead time of 3 months (range, 1-7 months). Seven studies showed that, on average, 67% (ranging from 20% to 80%) of the 798 relapsed patients had no clinical symptoms when recurrent ovarian cancer was diagnosed.
Routine follow-up may detect 2 of 3 recurrences asymptomatically with a lead time of 3 months. Recurrence treatment may extend survival by several months, but published studies did not show a survival advantage of early detection by routine follow-up examinations. Therefore, the content and aims of routine follow-up should be reconsidered, whereas routine cancer antigen 125 testing with the aim to improve life expectancy should be omitted.
International Journal of Gynecological Cancer 07/2011; 21(5):837-45. · 1.65 Impact Factor
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ABSTRACT: Routine follow-up is standard medical practice in ovarian cancer patients treated with curative intent. However, no strong evidence exists indicating that prognosis is improved. The objective of this study was to evaluate the routine follow-up schedule for ovarian cancer patients regarding the adherence to the Dutch protocol, the detection of recurrences, and the follow-up's impact on overall survival.
All 579 consecutive patients diagnosed with epithelial ovarian, primary peritoneal, or fallopian tube cancer in 4 Dutch hospitals between 1996 and 2006 were selected. Only patients in complete clinical remission after primary treatment were studied. Compliance to the Dutch follow-up guideline was assessed in a random sample of 68 patients. Of the 127 patients with recurrence, the mode of recurrence detection was addressed. Survival time since primary treatment was calculated using the Kaplan-Meier method.
The patients received more follow-up visits than was recommended according to the guideline. The cumulative 5-year risk of recurrence was 55% (95% confidence interval [CI], 43%-67%). The survival of patients with recurrent ovarian cancer detected asymptomatically at a routine visit (n = 51) tended to be better compared with patients with symptomatic detection at a routine (n = 31) or diagnosed after an interval visit (n = 31). The median survival times were 44 (95% CI, 38-64), 29 (95% CI, 21-38), and 33 months (95% CI, 19-61), respectively (P = 0.08). The median time from primary treatment to recurrence was similar for the 3 groups: 14, 10, and 11 months, respectively (P = 0.26).
Follow-up in line with (inter)national guidelines yields a seemingly longer life expectancy if the recurrence was detected asymptomatically. However, this result is expected to be explained by differences in tumor biology and length-time bias.
International Journal of Gynecological Cancer 05/2011; 21(4):647-53. · 1.65 Impact Factor
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ABSTRACT: Within blood establishments little comparative information is available about donors versus the general population. In this study, a description of the donor pool was made in terms of demographic factors and cardiovascular risk factors. The general Dutch population was used as a reference group.
The Donor InSight study provided information on donors. Extensive information has been gathered by a self-administered questionnaire addressing various topics, like demographics, lifestyle, and health. Aggregated donor responses were compared with general population summary data.
The study population consisted of 15,076 donors. The median age was 46.3 years and 47.3% were men. Donors were more likely to be highly educated (34.6%), married (71.7%), and of Dutch origin (97.4%), when compared to the general population. Donors were less often smokers (donors, 17.1%; general population, 31.8%), more often moderate drinkers (donors, 82.8%; general population, 74.7%), and physically more active (donors, 2.0 hr/week; general population, 1.0 hr/week). Male donors were more often moderately overweight (47.7%) than men from the general population (39.9%). In donors, 0.9% reported to have Type 2 diabetes versus 1.9% in the general population. In donors, 3.4% reported high cholesterol versus 4.6% in the general population.
The study provided important knowledge about demographic distributions and cardiovascular risk factors within donors. A proper understanding of demographic characteristics of donors will help us to focus recruitment and retention strategies. The reported beneficial cardiovascular profile suggests a need for further research on the role of blood donation in cardiovascular risk reduction.
Transfusion 02/2011; 51(2):412-20. · 3.22 Impact Factor
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ABSTRACT: The healthy donor effect has been mentioned as a methodologic problem in blood donor health research. The aim of this study was to investigate different elements of the healthy donor effect.
First, recent donors (<4 years registered as a donor) were compared with the general population. Second, active and lapsed donors were compared. Third, short-career donors (<14 donations) were compared with long-career donors (>37 donations). Various health and lifestyle indicators were used as outcome measures.
Compared to the general population, recent donors had a better self-rated health (odds ratio [OR], 1.43; 95% confidence interval [CI], 1.27-1.61), visited the general practitioner (GP) less often (OR, 0.66; 95% CI, 0.60-0.72), and were less often treated by a specialist (OR, 0.83; 95% CI, 0.75-0.93). Recent donors also exhibited a healthier lifestyle compared to the general population. When examining active versus lapsed donors, similar results were found in favor of active donors. With respect to donation career, long-career donors were healthier than short-career donors, but effects were less strong; the ORs were 1.33 (95% CI, 1.15-1.54) for self-rated health, 0.85 (95% CI, 0.76-0.94) for GP visit, and 0.83 (95% CI, 0.68-1.00) for specialist treatment. When comparing long- and short-career donors on lifestyle indicators, there were barely any significant differences.
The findings strongly point to the presence of a healthy donor effect when comparing donors with the general population and active versus lapsed donors. The healthy donor effect was less pronounced within active donors, when comparing long- and short-career donors. Therefore, health research should primarily be carried out within active donors.
Transfusion 02/2011; 51(8):1820-8. · 3.22 Impact Factor
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Daniel F Gudbjartsson,
Hilma Holm,
Olafur S Indridason,
Gudmar Thorleifsson,
Vidar Edvardsson,
Patrick Sulem, Femmie de Vegt,
Frank C H d'Ancona,
Martin den Heijer,
Jack F M Wetzels,
Leifur Franzson,
Thorunn Rafnar,
Kristleifur Kristjansson,
Unnur S Bjornsdottir,
Gudmundur I Eyjolfsson,
Lambertus A Kiemeney,
Augustine Kong,
Runolfur Palsson,
Unnur Thorsteinsdottir,
Kari Stefansson
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ABSTRACT: Chronic kidney disease (CKD) is a worldwide public health problem that is associated with substantial morbidity and mortality. To search for sequence variants that associate with CKD, we conducted a genome-wide association study (GWAS) that included a total of 3,203 Icelandic cases and 38,782 controls. We observed an association between CKD and a variant with 80% population frequency, rs4293393-T, positioned next to the UMOD gene (GeneID: 7369) on chromosome 16p12 (OR = 1.25, P = 4.1x10(-10)). This gene encodes uromodulin (Tamm-Horsfall protein), the most abundant protein in mammalian urine. The variant also associates significantly with serum creatinine concentration (SCr) in Icelandic subjects (N = 24,635, P = 1.3 x 10(-23)) but not in a smaller set of healthy Dutch controls (N = 1,819, P = 0.39). Our findings validate the association between the UMOD variant and both CKD and SCr recently discovered in a large GWAS. In the Icelandic dataset, we demonstrate that the effect on SCr increases substantially with both age (P = 3.0 x 10(-17)) and number of comorbid diseases (P = 0.008). The association with CKD is also stronger in the older age groups. These results suggest that the UMOD variant may influence the adaptation of the kidney to age-related risk factors of kidney disease such as hypertension and diabetes. The variant also associates with serum urea (P = 1.0 x 10(-6)), uric acid (P = 0.0064), and suggestively with gout. In contrast to CKD, the UMOD variant confers protection against kidney stones when studied in 3,617 Icelandic and Dutch kidney stone cases and 43,201 controls (OR = 0.88, P = 5.7 x 10(-5)).
PLoS Genetics 07/2010; 6(7):e1001039. · 8.69 Impact Factor
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Daniel F Gudbjartsson,
Hilma Holm,
Olafur S Indridason,
Gudmar Thorleifsson,
Vidar Edvardsson,
Patrick Sulem, Femmie de Vegt,
Frank C H d'Ancona,
Martin den Heijer,
Jack F M Wetzels,
Leifur Franzson,
Thorunn Rafnar,
Kristleifur Kristjansson,
Unnur S Bjornsdottir,
Gudmundur I Eyjolfsson,
Lambertus A Kiemeney,
Augustine Kong,
Runolfur Palsson,
Unnur Thorsteinsdottir,
Kari Stefansson
PLoS Genetics 01/2010; 6(11). · 8.69 Impact Factor
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Gudmar Thorleifsson,
Hilma Holm,
Vidar Edvardsson,
G Bragi Walters,
Unnur Styrkarsdottir,
Daniel F Gudbjartsson,
Patrick Sulem,
Bjarni V Halldorsson, Femmie de Vegt,
Frank C H d'Ancona, [......],
Thorunn Rafnar,
Kristleifur Kristjansson,
Gunnar Sigurdsson,
Lambertus A Kiemeney,
Magnus Bodvarsson,
Olafur S Indridason,
Runolfur Palsson,
Augustine Kong,
Unnur Thorsteinsdottir,
Kari Stefansson
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ABSTRACT: Kidney stone disease is a common condition. To search for sequence variants conferring risk of kidney stones, we conducted a genome-wide association study in 3,773 cases and 42,510 controls from Iceland and The Netherlands. We discovered common, synonymous variants in the CLDN14 gene that associate with kidney stones (OR = 1.25 and P = 4.0 x 10(-12) for rs219780[C]). Approximately 62% of the general population is homozygous for rs219780[C] and is estimated to have 1.64 times greater risk of developing the disease compared to noncarriers. The CLDN14 gene is expressed in the kidney and regulates paracellular permeability at epithelial tight junctions. The same variants were also found to associate with reduced bone mineral density at the hip (P = 0.00039) and spine (P = 0.0077).
Nature Genetics 07/2009; 41(8):926-30. · 35.53 Impact Factor
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Gudmar Thorleifsson,
Hilma Holm,
Vidar Edvardsson,
G Bragi Walters,
Unnur Styrkarsdottir,
Daniel F Gudbjartsson,
Patrick Sulem,
Bjarni V Halldorsson, Femmie de Vegt,
Frank C H d'Ancona, [......],
Thorunn Rafnar,
Kristleifur Kristjansson,
Gunnar Sigurdsson,
Lambertus A Kiemeney,
Magnus Bodvarsson,
Olafur S Indridason,
Runolfur Palsson,
Augustine Kong,
Unnur Thorsteinsdottir,
Kari Stefansson
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ABSTRACT: Kidney stone disease is a common condition. To search for sequence variants conferring risk of kidney stones, we conducted a genome-wide association study in 3,773 cases and 42,510 controls from Iceland and The Netherlands. We discovered common, synonymous variants in the
Nature Genetics 06/2009; 41(8):926-930. · 35.53 Impact Factor
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Thorgeir E Thorgeirsson,
Frank Geller,
Patrick Sulem,
Thorunn Rafnar,
Anna Wiste,
Kristinn P Magnusson,
Andrei Manolescu,
Gudmar Thorleifsson,
Hreinn Stefansson,
Andres Ingason, [......],
Lambertus A Kiemeney,
Stefan E Matthiasson,
Hogni Oskarsson,
Thorarinn Tyrfingsson,
Daniel F Gudbjartsson,
Jeffrey R Gulcher,
Steinn Jonsson,
Unnur Thorsteinsdottir,
Augustine Kong,
Kari Stefansson
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ABSTRACT: Smoking is a leading cause of preventable death, causing about 5 million premature deaths worldwide each year. Evidence for genetic influence on smoking behaviour and nicotine dependence (ND) has prompted a search for susceptibility genes. Furthermore, assessing the impact of sequence variants on smoking-related diseases is important to public health. Smoking is the major risk factor for lung cancer (LC) and is one of the main risk factors for peripheral arterial disease (PAD). Here we identify a common variant in the nicotinic acetylcholine receptor gene cluster on chromosome 15q24 with an effect on smoking quantity, ND and the risk of two smoking-related diseases in populations of European descent. The variant has an effect on the number of cigarettes smoked per day in our sample of smokers. The same variant was associated with ND in a previous genome-wide association study that used low-quantity smokers as controls, and with a similar approach we observe a highly significant association with ND. A comparison of cases of LC and PAD with population controls each showed that the variant confers risk of LC and PAD. The findings provide a case study of a gene-environment interaction, highlighting the role of nicotine addiction in the pathology of other serious diseases.
Nature 05/2008; 452(7187):638-42. · 36.28 Impact Factor
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Thorgeir E. Thorgeirsson,
Frank Geller,
Patrick Sulem,
Thorunn Rafnar,
Anna Wiste,
Kristinn P. Magnusson,
Andrei Manolescu,
Gudmar Thorleifsson,
Hreinn Stefansson,
Andres Ingason, [......],
Lambertus A. Kiemeney,
Stefan E. Matthiasson,
Hogni Oskarsson,
Thorarinn Tyrfingsson,
Daniel F. Gudbjartsson,
Jeffrey R. Gulcher,
Steinn Jonsson,
Unnur Thorsteinsdottir,
Augustine Kong,
Kari Stefansson
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ABSTRACT: Smoking is a leading cause of preventable death, causing about 5 million premature deaths worldwide each year
Nature 04/2008; 452(7187):638-642. · 36.28 Impact Factor
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ABSTRACT: Routine follow-up is offered to all patients with laryngeal cancer who are treated with curative intent. Although time and resources are devoted to surveillance, the effect of asymptomatic recurrence detection is not well understood. For this study, the authors evaluated the effect that routine follow-up may have on life expectancy and disease-specific mortality rate for patients with laryngeal cancer.
Using a Markov model, a cohort simulation was performed on 4 hypothetical age groups of patients with laryngeal cancer. Three different follow-up strategies were compared-the current schedule, no follow-up, and the perfect follow-up-in which all recurrences were detected asymptomatically. Sensitivity analyses were performed to study the impact of variations in the transition rates on life expectancy.
Compared with no follow-up, the current schedule showed a gain in life expectancy with a range from 0.3 years to 1.5 years that decreased with advancing age. Abolishing the current follow-up schedule raised the disease-specific mortality rate; the increase ranged from 2.8% to 5.9%. Variations of +/-25% in the transition rates produced only a modest effect on life expectancy.
A small reduction in life expectancy was observed when follow-up was withheld from the majority of patients. Disease-specific mortality rates rose when no follow-up was provided. These rates probably were overestimated. A simplified version of the current follow-up protocol may be implemented.
Cancer 02/2007; 109(2):239-47. · 4.77 Impact Factor
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ABSTRACT: We present a large European population-based study of thyroid function, performed in a population with longstanding borderline sufficient iodine intake.
The Nijmegen Biomedical Study is a population-based survey conducted in the eastern part of The Netherlands. Randomly selected inhabitants received a postal questionnaire on lifestyle and medical history, which was filled out by 9371 individuals (41.7%). We measured serum thyroid-stimulating hormone (TSH), free thyroxine (FT4), and anti-thyroperoxidase antibodies (TPOAbs) in 6434 responders. A reference population of 5167 individuals was selected by excluding those at risk for thyroid disease.
Overt thyrotoxicosis was found in 0.4% of the total population and subclinical thyrotoxicosis in 0.8%. Overt hypothyroidism was found in 0.4% and subclinical hypothyroidism in 4.0%. In individuals older than 60 years, mean FT4 concentrations increased with age. Mean TSH decreased with age, from 1.46 mIU/L at 18-24 years to 1.07 mIU/L after 85 years. The mean TSH in the total population did not differ from the mean TSH in the reference population; the exclusion of those at risk for thyroid disease, however, lowered the upper limit of the TSH reference interval considerably. In the total population, 8.6% of males and 18.5% of females had positive TPOAbs. The presence of TPOAbs was associated with abnormally high and low TSH concentrations.
In inhabitants of the eastern part of The Netherlands, serum TSH gradually decreases with age, whereas after age 60, serum FT4 increases, possibly because of the development of thyroid autonomy after longstanding borderline sufficient iodine intake.
Clinical Chemistry 02/2006; 52(1):104-11. · 7.91 Impact Factor
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Thorunn Rafnar,
Patrick Sulem,
Simon N Stacey,
Frank Geller,
Julius Gudmundsson,
Asgeir Sigurdsson,
Margret Jakobsdottir,
Hafdis Helgadottir,
Steinunn Thorlacius,
Katja K H Aben, [......],
Rosa B Barkardottir,
Eirikur Jonsson,
Steinn Jonsson,
Jon H Olafsson,
Jeffrey R Gulcher,
Gisli Masson,
Daniel F Gudbjartsson,
Augustine Kong,
Unnur Thorsteinsdottir,
Kari Stefansson
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ABSTRACT: The common sequence variants that have recently been associated with cancer risk are particular to a single cancer type or at most two. Following up on our genome-wide scan of basal cell carcinoma, we found that rs401681[C] on chromosome 5p15.33 satisfied our threshold for genome-wide significance (OR = 1.25, P = 3.7 x 10(-12)). We tested rs401681 for association with 16 additional cancer types in over 30,000 cancer cases and 45,000 controls and found association with lung cancer (OR = 1.15, P = 7.2 x 10(-8)) and urinary bladder, prostate and cervix cancer (ORs = 1.07-1.31, all P < 4 x 10(-4)). However, rs401681[C] seems to confer protection against cutaneous melanoma (OR = 0.88, P = 8.0 x 10(-4)). Notably, most of these cancer types have a strong environmental component to their risk. Investigation of the region led us to rs2736098[A], which showed stronger association with some cancer types. However, neither variant could fully account for the association of the other. rs2736098 corresponds to A305A in the telomerase reverse transcriptase (TERT) protein and rs401681 is in an intron of the CLPTM1L gene.
