Severity: Warning
Message: file_get_contents(https://...@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
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Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
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Function: file_get_contents
File: /var/www/html/application/helpers/my_audit_helper.php
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Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
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Function: getPubMedXML
File: /var/www/html/application/controllers/Detail.php
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Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
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Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
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Function: require_once
Severity: Warning
Message: Attempt to read property "Count" on bool
Filename: helpers/my_audit_helper.php
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Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3100
Function: _error_handler
File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
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Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
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Function: require_once
Background: NBN 657del5 founder mutation predisposes to breast and prostate cancer. Recently, it has been reported that the pathogenicity of this mutation with regard to prostate cancer risk is modified by a missense variant of the same gene (E185Q).
Methods: To evaluate the interaction of the 657del5 and E185Q founder alleles of NBN on breast cancer risk in Poland, 4964 women with breast cancer and 6152 controls were genotyped for these two recurrent variants of NBN (657del5 truncating variant and E185Q missense variant).
Results: The NBN 657del5 mutation was detected in 57 of 4964 unselected cases and in 35 of 6152 controls (OR = 2.0, p = 0.001). The E185Q GG genotype was detected in 2167 of 4964 unselected cases and in 2617 of 6152 controls (OR = 1.04, p = 0.3). In carriers of the 657del5 deletion, the elevated cancer risk was restricted to women with the GG genotype of the E185Q variant (OR = 3.6, 95% CI 1.9-6.6; p < 0.0001). Among women with other E185Q genotypes, the OR associated with 657del5 was 1.0 (95% CI 0.5-1.8; p = 0.9). The interaction between the two alleles was statistically significant (homogeneity p = 0.003).
Conclusion: In Poland, the pathogenicity of the NBN 657del5 mutation is restricted to women with a homozygous GG genotype of missense variant of the same gene (E185Q). This is the first clear example whereby a moderate penetrance breast cancer gene is impacted by a genetic modifier.
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Source |
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http://dx.doi.org/10.1007/s10549-019-05391-w | DOI Listing |
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