These findings suggest that genetic polymorphisms in the DNA repair genes may modulate overall lung cancer susceptibility and that pathological stage and XRCC1 Arg399Gln independently predicted overall survival among Indian lung cancer patients.

Identifying genes associated with familial inheritance of breast cancer continues to be a major goal of current research as the known high penetrance genes could be attributable for only a small percentage of the risk. So, it is hypothesized that the low penetrance genes may also modify the risk for familial breast cancer. In the present case-control study, undertaken to examine the influence of polymorphisms of GSTs in familial and sporadic breast cancer susceptibility, 597 women including 222 sporadic breast cancer patients, 125 familial breast cancer patients and 250 females with no history of cancer as controls were genotyped by PCR based methods. Odds Ratios (ORs) and 95% Confidence Intervals (95%CIs) were calculated by unconditional logistic regression adjusted to age. Interestingly, GSTM1 deletion was found to be significantly associated only with familial breast cancer (OR = 2.0; 95%CI = 1.252-3.128) while GSTT1 was associated only with sporadic breast cancer (OR = 2.3; 95%CI = 1.336-3.970). GSTP1 Ile105Val polymorphism was associated neither with sporadic nor familial breast cancer susceptibility (P value > 0.05). The GST genotypes did not have any effect on the survival of both familial and sporadic breast cancer patients. However, familial breast cancer patients with GSTM1 null genotype had a relative risk of 0.42 (95%CI = 0.18-0.97) for an advanced disease stage. The results indicate that, in addition to the known high penetrance genes, certain low penetrance genes may also play a role, in the familial inheritance of breast cancer. It is also noticed that all the polymorphisms associated with sporadic breast cancer are not associated with familial breast cancer.

This case control study investigated whether polymorphisms of estrogen metabolizing genes CYP1A1 MspI, CYP17 MspAI, COMT Val(158) Met, and SULT1A1 Arg(213) His have any role in familial breast cancer susceptibility risk. Logistic regression analysis adjusted to age was used to calculate odds ratios (ORs) and 95% confidence intervals (95%CIs). Familial breast cancer risk due to CYP1A1 wt/m1 and m1/m1 genotypes was 2.3 (1.51-3.61)-fold and 7.1 (3.69-13.7)-fold, respectively. In addition to the main effects, certain first-order interactions were also significantly associated with familial breast cancer. Our results favor a possible risk modification by estrogen metabolizing gene polymorphisms in familial breast cancer susceptibility.

The etiology of a significant proportion of familial breast cancers is still poorly understood, with known high penetrance gene mutations accounting for only a small proportion of the cases. The increased risk of breast cancer for the majority of women with a family history likely reflects shared minor low penetrant genetic factors. In the present case-control study undertaken to examine the influence of DNA damage repair gene polymorphisms in familial and sporadic breast cancer susceptibility, 219 Sporadic and 140 familial breast cancer patients and 367 controls were genotyped using PCRRFLP. Odds Ratios (ORs) and 95% Confidence Intervals (95%CIs) were calculated by unconditional logistic regression adjusted to age. Variant genotypes XRCC1 Arg/Gln or Gln/Gln and XPD Lys/Gln or Gln/Gln increased both familial and sporadic breast cancer susceptibility. However, when the intra group risk was compared, the risk due to the XPD polymorphic genotypes Lys/Gln or Gln/Gln was significantly lower among familial breast cancer patients compared to sporadic breast cancer patients [OR = 0.61; 95%CI = 0.39-0.94; p value = 0.024) whereas the risk implied by XRCC1 variant genotype was not significantly different between the familial and nonfamilial groups of breast cancer patients [OR = 0.97; 95%CI = 0.63-1.49; p value = 0.882]. Both these variant genotypes were not associated with the disease characteristics or survival of either familial or sporadic breast cancer patients. This study represents an addition to previous published work on GSTs from the same study population and substantiates the hypothesis that the impact of the low penetrance gene polymorphisms differ by family history of the disease.

The results of this study suggest that germline mutations of BRCA2 gene account for rather small proportion of Hereditary Breast/Ovarian cancer in Kerala, South India.