| 1. |
- Ajore, Ram, et al.
(författare)
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Functional dissection of inherited non-coding variation influencing multiple myeloma risk
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Thousands of non-coding variants have been associated with increased risk of human diseases, yet the causal variants and their mechanisms-of-action remain obscure. In an integrative study combining massively parallel reporter assays (MPRA), expression analyses (eQTL, meQTL, PCHiC) and chromatin accessibility analyses in primary cells (caQTL), we investigate 1,039 variants associated with multiple myeloma (MM). We demonstrate that MM susceptibility is mediated by gene-regulatory changes in plasma cells and B-cells, and identify putative causal variants at six risk loci (SMARCD3, WAC, ELL2, CDCA7L, CEP120, and PREX1). Notably, three of these variants co-localize with significant plasma cell caQTLs, signaling the presence of causal activity at these precise genomic positions in an endogenous chromosomal context in vivo. Our results provide a systematic functional dissection of risk loci for a hematologic malignancy.
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| 4. |
- Bevier, Melanie, et al.
(författare)
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Incidence of cancer of unknown primary in Sweden: analysis by location of metastasis.
- 2012
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Ingår i: European Journal of Cancer Prevention. - 1473-5709. ; 21:6, s. 596-601
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Tidskriftsartikel (refereegranskat)abstract
- Increasing incidences of cancer of unknown primary (CUP) have been observed in Sweden previously. However, it is not known how the incidence trends for specific locations of metastasis vary. Site-specific data are available on the basis of the ninth international classification of diseases. CUP patients were identified between 1987 and 2008 from the Swedish Family-Cancer Database. Malignant neoplasms of ill-defined sites were diagnosed in 4042 patients, 1976 developed metastasis in lymph nodes, 9615 had metastasis in specified organs, and in 8052 patients, the malignant neoplasm was diagnosed without further specification. Age-standardized incidence rates for 23 685 patients were analyzed using a direct method of standardization. Overall, the incidence of CUP decreased from 6.98 to 6.00 per 100 000 from 1987 to 2008. The number of patients diagnosed with metastasis in specified organs decreased, whereas the number of patients diagnosed with CUP without further specification increased from 2.65 to 3.02 per 100 000. With improvements in diagnostic methods and imaging techniques for identification of cancer, the incidences of CUP have been decreasing because primary tumors can be specified more often. Computed tomography is typically sensitive in detecting lung, kidney, and colorectal cancers, which are known to have a genetic link with CUP. Prostate-specific antigen testing is used to detect prostate cancer, for which bone is a common metastatic site. Liver metastases are common if the primary tumor is located in the colorectum. If the primary tumor is found, this cancer site replaces the diagnosis of CUP within the Cancer Register and therefore CUP incidence is decreased.
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| 5. |
- Bevier, Melanie, et al.
(författare)
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Influence of family size and birth order on risk of cancer: a population-based study
- 2011
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Family size and birth order are known to influence the risk of some cancers. However, it is still unknown whether these effects change from early to later adulthood. We used the data of the Swedish Family Cancer Database to further analyze these effects. Methods: We selected over 5.7 million offspring with identified parents but no parental cancer. We estimated the effect of birth order and family size by Poisson regression adjusted for age, sex, period, region and socioeconomic status. We divided the age at diagnosis in two groups, below and over 50 years, to identify the effect of family size and birth order for different age periods. Results: Negative associations for increasing birth order were found for endometrial, testicular, skin, thyroid and connective tissue cancers and melanoma. In contrast, we observed positive association between birth order and lung, male and female genital cancers. Family size was associated with decreasing risk for endometrial and testicular cancers, melanoma and squamous cell carcinoma; risk was increased for leukemia and nervous system cancer. The effect of birth order decreased for lung and endometrial cancer from age at diagnosis below to over 50 years. Combined effects for birth order and family size were marginally significant for thyroid gland tumors. Especially, the relative risk for follicular thyroid gland tumors was significantly decreased for increasing birth order. Conclusion: Our findings suggest that the effect of birth order decreases from early to late adulthood for lung and endometrial cancer.
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| 6. |
- Bevier, Melanie, et al.
(författare)
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Risk of breast cancer in families of multiple affected women and men
- 2012
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 1573-7217 .- 0167-6806. ; 132:2, s. 723-728
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Tidskriftsartikel (refereegranskat)abstract
- Family history of first and second-degree relatives is known to increase the risk for breast cancer. Less data are available on the risks between defined multiple affected close and distant relatives for which the reliability of data may be an issue. Data on affected males are sparse. These questions and the probable genetic models were addressed in this study by means of a nationwide Swedish Family-Cancer Database. We estimated the effect of family history of breast cancer by Poisson regression for women of at least 30 years of age after adjusting for age, period, region, socioeconomic status, number of children, and age at first birth. The results of the study showed that relative risk (RR) for breast cancer was associated with a first degree as well as second-degree family history. Having at least two female affected first-degree relatives increased the RR at least to 2.8, favoring an additive interaction. The risk was increased around ten times in women with both parents affected. When either a father or a mother was affected, the RRs were nearly identical (RR = 1.73 and 1.74, respectively). The RR for a woman increased more when a brother was affected (RR = 2.48) compared to when a sister was affected (RR = 1.87). Having an affected grandmother showed lower familial excess risks than having an affected half sister (RR = 1.27, and 1.26; and RR = 1.39, and 1.50; respectively, for maternal and paternal relatives). We concluded that when both parents were diagnosed with breast cancer, the risk for the daughter was increased tenfold. Having an affected brother showed a somewhat higher risk than having an affected sister. The data suggest that male breast cancer has a higher genetic basis than female breast cancer, which invites further search of the underlying mechanisms.
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| 7. |
- Bosetti, Cristina, et al.
(författare)
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High constant incidence rates of second primary cancers of the head and neck: a pooled analysis of 13 cancer registries
- 2011
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 129:1, s. 173-179
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Tidskriftsartikel (refereegranskat)abstract
- Scanty data are available on the incidence (i.e., the absolute risk) of second cancers of the head and neck (HN) and its pattern with age. We investigated this issue using data from a multicentric study of 13 population-based cancer registries from Europe, Canada, Australia and Singapore for the years 1943-2000. A total of 99,257 patients had a first primary HN cancer (15,985 tongue, 22,378 mouth, 20,758 pharyngeal, and 40,190 laryngeal cancer), contributing to 489,855 person-years of follow-up. A total of 1,294 of the patients (1.3%) were diagnosed with second HN cancers (342 tongue, 345 mouth, 418 pharynx and 189 larynx). Male incidence rates of first HN cancer steeply increased from 0.68/100,000 at age 30-34 to 46.2/100,000 at age 70-74, and leveled off at older age; female incidence increased from 0.50/100,000 at age 30-34 to 16.5/100,000 at age 80-84. However, age-specific incidence of second HN cancers after a first HN cancer in men was around 200-300/100,000 between age 40-44 and age 70-74 and tended to decline at subsequent ages (150/100,000 at age 80-84); in women, incidence of second HN cancers was around 200-300/100,000 between age 45-49 and 80-84. The patterns of age-specific incidence were consistent for different subsites of second HN cancer and sexes; moreover, they were similar for age-specific incidence of first primary HN cancer in patients who subsequently developed a second HN cancer. The incidence of second HN cancers does not increase with age, but remains constant, or if anything, decreases with advancing age.
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| 8. |
- Brandt, Andreas, et al.
(författare)
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Age at Diagnosis and Age at Death in Familial Prostate Cancer
- 2009
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Ingår i: The Oncologist. - : Oxford University Press (OUP). - 1083-7159 .- 1549-490X. ; 14:12, s. 1209-1217
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. A family history of prostate cancer is associated with a higher risk for prostate cancer to first-degree relatives. If greater surveillance of men at familial risk is considered to be useful, population-based estimates of the differences in the age at diagnosis between familial and sporadic prostate cancer cases are needed. Methods. The men in the nationwide Swedish Family-Cancer Database were classified according to the number and type of affected first-degree relatives (father or brother) and according to the relative's age at diagnosis. The cumulative incidence of prostate cancer and cumulative prostate cancer-specific mortality were estimated using a stratified Cox model. Results. The cumulative incidence was highest for men with multiple affected first-degree relatives, and it was higher for brothers than for sons of prostate cancer patients. The age to reach the same cumulative incidence as the general population at age 55 years decreased with decreasing age at diagnosis of the relative, ranging from 48.7 years (father diagnosed before 60 years of age) to 53.7 years (father diagnosed after 82 years of age). Prostate cancer-specific mortality was also related to the number and type of affected relatives but there was no clear evidence for a dependency on the age at diagnosis of the relative. Conclusions. Men with a father or a brother affected by prostate cancer are diagnosed and die at earlier ages than men without a family history of prostate cancer. This study should encourage further analysis in order to assess the risks and benefits of screening for prostate cancer in men at higher risk. The Oncologist 2009; 14: 1209-1217
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| 9. |
- Brandt, A., et al.
(författare)
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Age of onset in familial breast cancer as background data for medical surveillance
- 2010
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 102:1, s. 42-47
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Familial breast cancers are known to be of early onset. This article provides differences in the age of onset of breast cancer and death by breast cancer between women with and without a family history. METHODS: The Swedish Family-Cancer Database was used to estimate the cumulative risk of breast cancer and death by breast cancer according to family history with a stratified Cox model. Family history was defined separately for affected mother or sister considering their diagnostic ages. RESULTS: The age to reach the same cumulative incidence as women without family history decreased with decreasing diagnostic age of the affected relative. Women with a maternal history reached the risk of women lacking a family history at the age of 50 years between 12.3 (mother affected < 40 years) and 3.3 years (mother affected > 82 years) earlier. The trend for breast cancer mortality was essentially similar. CONCLUSIONS: Women with mother or sister affected by breast cancer are diagnosed and die at earlier ages than do women without family history. The differences depend on the diagnostic age of the affected relative. The present data may provide a rationale to derive recommendations for the starting age of screening in women with affected family members. British Journal of Cancer (2010) 102, 42-47. doi:10.1038/sj.bjc.6605421 www.bjcancer.com Published online 10 November 2009 (C) 2010 Cancer Research UK
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| 10. |
- Brandt, Andreas, et al.
(författare)
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Breast cancer risk in women who fulfill high-risk criteria: at what age should surveillance start?
- 2010
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 1573-7217 .- 0167-6806. ; 121:1, s. 133-141
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Tidskriftsartikel (refereegranskat)abstract
- Family history is a strong predictor of hereditary breast cancer, particularly when it includes cases of early onset or bilateral breast cancers and multiple cases of breast or ovarian cancers. This article provides relative risks and cumulative risks of breast cancer in women whose family history indicates high risk. Specifically, the aim was to determine how many years earlier the high-risk women reach the cumulative risk of women without family history at the age at which screening in average-risk women is initiated. The women of the nation-wide Swedish Family-Cancer Database were classified according to clinical criteria based on family history suggesting high risk for hereditary breast ovarian cancer syndrome. The relative risks of breast cancer were calculated as hazard ratio using Cox regression. Cumulative risks of breast cancer were estimated with a stratified Cox model based on Tsiatis' method. The hazard ratios of breast cancer for the considered criteria ranged from 1.50 to 5.99. The cumulative risks ranged from 1 to 10% by age 50 years. The age to reach the same cumulative risk as women lacking a family history at the age of 50 years ranged between 32.0 and 40.8 years. Relative and cumulative risks of women at high risk of breast cancer associated with different clinical criteria were diverse, which may be helpful in considering when current clinical criteria are revised. According to the present results, current recommendations of starting clinical interventions 10 years earlier in high-risk women, based on expert opinions, appear justified at least for the largest high-risk groups.
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